A B S T R A C T

The plants of Celtis L. genus have been traditionally used to cure aches, sore throats, fevers, cancer, sexually transmitted diseases, sexual weakness, diarrhea, stomach problems, amenorrhea, menstrual disorders, kidney stones, and pain. The review aims to give a comprehensive account of the current state of ethnopharmacology, phytochemistry, and biological activities of the Celtis genus, as well as to describe the potential area of future avenues. Information on the Celtis genus was obtained from internet sources such as Google Scholar, Web of Science, PubMed, Science- Direct, and so on by using appropriate keywords, including ethnobotanical, pharmacological, pharmaceutical, bioactivity, phytochemistry, and botanical features of the Celtis genus. This re- view identified 14 species in the genus Celtis that have a phytopharmacological investigation, including C.africana Burm. f., C. australis L., C. occidentalis L., C. sinensis Pers., C. philippensis Blanco., C. tetrandra Roxb., C. tessmannii Rendle., C. jessoensis Koidz., C. adolfi-friderici Engl.,

C. iguanaea (Jacq.) Sarg., C. laevigata Wild., C. pallida Torr., C. zenkeri Engl., and C. tournefortii Lam. This genus contains many classified phytoconstituents, such as terpenoids, organic acids, flavonoids, and volatile compounds. Their extracts and pure substances have been shown to have

the same anticancer, antibacterial, anti-inflammatory, antioxidant, hepatoprotective, car-

dioprotective, urease-inhibiting, and antidiarrheal properties as their traditional uses. In terms of current information on ethnopharmacology, phytochemicals, and pharmacological uses, the data acquired in this review could be beneficial and needed for future research. Some phytocon- stituents (for instance, kaempferol, myricetin, quercetin, and eugenol) and extracts (for example, leaves, seeds, and ripe fruits extracts of C. australis) showed tremendous results in preliminary testing with promising antimicrobial, anticancer, and urease inhibitory effects. Further research and clinical investigations are needed to develop them as lead compounds and neutraceuticals, which may provide an advance over traditional medicinal systems.

Abbreviations

2D-NMR Two-dimensional Nuclear Magnetic Resonance A2780 Human Ovarian Cancer

A549 Adeno-Carcinomic Human Alveolar Basal Epithelial Cells ACF Aberrant Crypt Foci

AGS Human Gastric Adenocarcinoma Cells Bcl2 B-Cell Leukemia 2

CAT Catalase

C-NMR Carbon-13 Nuclear Magnetic Resonance

COX-2 Cyclooxygenase-2

CYP-1A1 Cytochrome P450 Family 1 Subfamily A Member 1 DAD Diode-Array Detection

DPPH 2,2-Diphenyl-1-Picrylhydrazyl

ESI-MS Electrospray Ionization Mass Spectroscopy

ERK1/2 Extracellular Signal-Regulated Kinase ½

EI-MS Electron Ionization Mass Spectroscopy FID Flame Ionization Detector

FT-IR Fourier Transform Infrared Spectroscopy FRAP Ferric Reducing Ability of Plasma

GC-MS Gas Chromatography Mass Spectroscopy GSH Glutathione

HCT-116 Human Colon Cancer Cell line

H-NMR Proton Nuclear Magnetic Resonance

HPLC High-Performance Liquid Chromatography

HR-FAB-MS High-Resolution Fast Atom Bombardment Mass Spectroscopy HRESIMS High-Resolution Electrospray Ionization Mass Spectrometry HREIMS High-Resolution Electron Ionization Mass Spectrometry

HMG-CoA Reductase 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase

iNOS Inducible Nitric Oxide Synthase IR Infrared Spectroscopy

JNK Jun N-Terminal Kinases

KAS Beta-Ketoacyl-[acyl Carrier Protein]-Synthase LC-MS Liquid Chromatography Mass Spectroscopy LDL Low-Density Lipoprotein

MIC Minimum Inhibitory Concentration MBC Minimum Bactericidal Concentration mir-26b MicroRNA 26b

mir-146a MicroRNA 146a

MRSA Methicillin-Resistant Staphylococcus aureus

MS Mass Spectroscopy mRNA Messenger RNA

NMDAR N-Methyl-D-Aspartate-Receptor PC-3 Human Prostate Cancer Cell line QS Quorum Sensing

RSH Reactive Thiol Group,

SFE-CO2 Supercritical Fluid Extraction of CO2

SOD Superoxide Dismutase

TBARS Thiobarbituric Acid Reactive Substances TOF/MS Time of Flight Mass Spectroscopy

TRAIL Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, TNF-α Tumor Necrosis Factor-Alpha

UHPLC Ultra High-Pressure Liquid Chromatography

UV Ultraviolet Spectroscopy

QqQ-MS Triple Quadrupole Mass Spectroscopy BHT Butylated Hydroxytoluene

BHA Butylated Hydroxyanisole

MAPK Mitogen-Activated Protein Kinase

SHP2 Src Homology Region 2 (SH2)-Containing Protein Tyrosine Phosphatase 2 STAT Signal Transducers and Activators of Transcription

Scientific names

B. cereus Bacillus cereus

B. megaterium Bacillus megaterium

B. subtilis Bacillus subtilis

C. albicans Candida albicans

C. freundii Citrobacter freundii

C. neoformans Cryptococcus neoformans

C. parapsilosis Candida parapsilosis

C. tropicalis Candida tropicalis

E. aerogenes Enterobacter aerogenes

E. coli Escherichia coli

K. pneumonia Klebsiella pneumonia

L. ivanovii Listeria ivanovii

L. monocytogenes Listeria monocytogenes

M. avium Mycobacterium avium

M. tuberculosis Mycobacterium tuberculosis

P. aeruginosa Pseudomonas aeruginosa

P. falciparum Plasmodium falciparum

P. mirabilis Proteus mirabilis

P. vulgaris Proteus vulgaris

R. mucilaginosa Rhodotorulamucilaginosa

S. aureus Staphylococcus aureus

P. aeruginosa Pseudomonas aeruginosa

Introduction

Scientists have explored natural sources for discovering novel therapeutic compounds throughout the ages [1–3]. This effort has resulted in the discovery of several therapeutic plants that can potentially cure various diseases [4–6]. Interestingly, almost 80 % of the world’s population relies heavily on natural approaches to health care needs [7–9]. These medicinal plants’ ability to promote re-

covery is due to their varied chemical compounds, which have abundant biological impacts on living beings [10,11]. In particular, these biologically active phytomolecules are the source of many pharmacological medicines [12]. For instance, medicinal plants feature antimalarial molecules like quinine, cardioactive drugs like digoxin, narcotic pain relievers like morphine, and anti-neoplastic therapies like vincristine and vinblastine [13]. Therefore, potent medicinal plant genus may play a vital role in discovering new lead medicinal molecules.

The Celtis genus is one of the potential sources of medicinal compounds that exhibit prosperous ethnopharmacological properties. Almost every portion of these plants (leaves, barks, roots, saps, etc.) historically utilized in traditional treatments for a wide array of

diseases such as diabetics, venereal, gastrointestinal, amenorrhea, pain, headache, and fever [14–26]. A wide range of biochemical

activities have been revealed by preliminary biological and therapeutic assessments of extracts and secondary metabolites of Celtis

species. These encompass anti-cancer, anti-inflammatory, antimicrobial, analgesic, antifungal, antidiabetic, and antioxidant features [25,27–38].

Identified chemicals from Celtis plants show potential in the fight against antimicrobial resistance (AMR), while AMR is an urgent

problem that led to almost 3.57 million deaths worldwide in 2019 [39]. For the managing such AMR threats, the antimicrobial activity of the medicinal plants poses a new hope [40]. Moreover, the antibacterial efficacy of the Celtis plant’s molecules, including eugenol, palmitic acid, and stearic acid has been noted against resistant strains [41,42]. These phytoconstituents could be used as a starting point to find novel antibiotic compounds that can reduce AMR cases.

However, the therapeutic details of Celtis’s compounds is still limited, especially in regard to their efficacy, mode of action,

therapeutic index, and probable toxicity. A thorough analysis of the Celtis genus is required to clarify its present status and inform future investigation scope to the researcher, because most of the findings made until now are in the preliminary stage. While one review has concentrated on a single Celtis species, Celtis australis [43], many other species of the Celtis genus have not been rigorously reviewed. This comprehensive review of the Celtis genus is required to fill this knowledge gap.

Celtis is the genus of hackberries or nettle trees belonging to the Cannabaceae family, is mainly distributed in Africa, Asia, northern Australia, and South and North America [44,45]. Formerly, Celtis plants were allocated as either Ulmaceae or a new family, Celti- daceae. However, Celtis is now classified under the Cannabaceae family [46]. According to the Plant List 2022, 349 scientific names of the genus Celtis are documented, including 69 accepted names, 222 synonym species, and 55 unaccessible data (www.theplantlist.org). This unique genus can be separated from other genera of its family, especially by leaf characteristics: deciduous, alternate, and distichous with three veins rather than one vein. Flowers are small, greenish, and either unisexual or bisexual. Fruits are fleshy and one-seeded [47].

From this comprehensive review, considering the botanical, pharmacological, biological, and phytochemistry aspects of species from the genus Celtis, only 14 species have been evaluated for the extensive analyses as per our knowledge, which include C. africana Burm. f., C. australis L., (synonym: Celtis australis var. eriocarpa Decne.),C. occidentalis L., C. sinensis Pers.,C. philippensis Blanco.,

C. tetrandra Roxb.,C. tessmannii Rendle.,C. jessoensis Koidz., (Synonym: C. choseniana Nakai), C. adolfi-friderici Engl.,C. iguanaea (Jacq.) Sarg. (synonym: C. ehrenbergiana (Klotzsch) Liebm.),C. laevigata Wild., C. pallida Torr., C. zenkeriEngl., andC. tournefortii Lam. (syn- onym: C. aetnensis (Tornab.) Strobl). Among them, C. africana Burm. f., C. australis L., and C. sinensis Pers. were the most often evaluated species across a broad range of ailments. This review aims to gather the present state knowledge from the ethno- pharmacological to the phytopharmacological value of the genus Celtis for future studies. The existing knowledge of phytochemical components with their characterization data and medicinal uses of this genus is reviewed to accelerate the discovery of new lead compounds.

Methods

1. The search strategy

The relevant data of the genus Celtis was collected via electronic resources such as Google Scholar, PubMed, Web of Science, and ScienceDirect using search terms “ethnobotanical use of Celtis”, “pharmacological use of Celtis”, “pharmaceutical use of Celtis”, “bioactivity of Celtis”, “phytochemistry of Celtis”, and “botanical characteristics of Celtis”. This review included the relevant websites, journal articles, Ph.D. thesis, and books.

1. Inclusion and exclusion criteria

From 1881 to 2023, a total of 2514 articles were collected by searching keywords rigorously. Where, only 1479 abstracts were matched with this study’s title and aims. Relevant websites, journal articles, books, and Ph.D. thesis were collected, while 202 pertinent sources were short-listed (Fig. 1). Duplicates, lack of full text, abstract not available in English, withdrawn or retracted articles, lack of ethnopharmacology and phytochemical investigation were eliminated (n 899) (Fig. 1). The details of this review methodology based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were sketched in Fig. 1.

1. Software and database

All chemical synonyms were taken from the PubChem database, while synonymous scientific names were taken from the Plant List 2022 website (www.theplantlist.org). Chemical structures of the phytoconstituents were drawn with ChemDraw 16.0 (PerkinElmer Informatics, in Waltham, MA).

Fig. 1. The article selection procedure following the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols.

Botany and distribution of Celtis genus.

Scientific name	Distribution	Leaves	Fruits	Flowers	References
C. adolphi-	Togo, Benin, Democratic Republic	Alternate, simple, broadly	Fleshy, sub-globose	The flowers are small with a	[49]

friderici

of Congo, Uganda, Guinea, Ivory Coast, Ghana

elliptic, mesophyll, entire, glabrous

white corolla.

C. africana From West Africa to Sudan,

Arabia, Angola, and the Cape Province of South Africa.

C. australis From West Asia to the

Mediterranean, including Morocco, Spain, Syria, the Caucasus, and Central and Northern Europe.

Simple alternate, egg- shaped, soft hairy, asymmetrical and has three veins raised from the base.

Simple, cauline, alternate, stipulate, and hairy stipules and petiolate.

Yellowish-colored fruits are found from October to February.

Harvested in the autumn and with a single seed

Unisexual, greenish, small, and raised in springs.

From March to April, green, small, unisexual flowers bloom.

[27,50,51]

[52–54]

C. choseniana North Korea, and South Korea. Pale green, deciduous,

narrow or wide ovate, papery, glabrous upper, and glaucous lower leaves.

Orange-yellow, ellipsoidal to globose, and solitary fruit

Flowers placed in tightly packed cymes

[55]

C. iguanaea From New Mexico east to Virginia,

Illinois south to Florida, and New Mexico west to Virginia.

Native to South America, Central America, and North America

The tops of the leaves are pale greenish-yellow, and the bottoms are pale green.

Oval to broadly elliptic, wide, acute or attenuate at the apex, obtuse to subcordate at the base.

Ovid shaped, orange or brownish-red colored long fruit comes from September to October.

Flowers bloom in mid-May and grow in separate or small clusters.

Greenish-yellow, bisexual, cylindrical ovary, hairy, staminate flowers.

[47,

56–58]

C. occidentalis In North America, east of

Mississippi, Ontario, and eastern Canada; the Southeastern US; the Southern Appalachian States; and Northwest Italy.

The leaves have three principal veins. oblong or lanceolate in shape.

Reveal in September to October. Purple or brownish, fleshy, thin skin, one seed, globular fruit.

In bloom in April and May [47,56]

C. pallida From the south to the middle of

America, Arizona, Florida, New Mexico, and Texas.

C. philippensis Madagascar, India, Myanmar,

Southeast China, Taiwan, Thailand, Malaysia, Northeast and West Australia, and the Solomon Islands.

Ovate to ovate-oblong shape, rounded apex, rough surfaces.

Elliptical to lanceolate, ovate-elliptical shape

It may be yellow, orange, or red.

The color ranges from orange to red, and the shape ranges from globose to ellipsoid, with an obtusely rounded base.

It blooms from March to May.

Cluster cyme has five bisexual flowers and five or more male flowers.

[59]

[60,61]

C. sinensis China, Taiwan, Korea, and Japan Ovate or ovate-elliptic,

hair scatters from major veins.

Fasciculate in the leaf axils and at the stem bases. Style branches are linear and undivided, and bloom in March or April.

Stone white flowers bloom in September or October.

[61,62]

C. tessmanni Native to Gabon, Cameroon,

Congo, Central Republic of Africa.

Elliptic-shaped leaves Fruits may be orange or

black

Hermaphrodites stay at the apex of cymes crowded with male flowers.

[45]

C. tournefortii Ukraine, Croatia, Greece, Cyprus,

northwestern Iran, northern Iraq, Turkey, and the Caucasus region, Azerbaijan.

Oval to narrowly oval, acute to sub acuminate leaves

Matured fruits are yellow to orange in color.

Blooms March–April [33,63]

C. zenkeri From Ivory Coast to Angola,

Uganda, Tanzania

Oblong-elliptic to ovate, shortly acuminate, 3- nerved from the base

Sub-globose or ovoid, red, pubescent or subglabrous.

Lower with clustered male

flowers, often with 1–2 female or hermaphrodite flowers at the top.

[64]

Botany

1. Taxonomy

The Celtis genus is a member of the Plantae kingdom, Viridiplantae subkingdom, Streptophyta infrakingdom, Embry- ophytasuperdivision, Tracheophyta division, Spermatophytina subdivision, Magnoliopsida class, Rosanae superorder, Rosales order, and Cannabaceae family [48].

Table 2

The traditional uses of Celtisgenus.

preparation

Species	Part used	Method of	Medicinal uses	Region	References
C. adolphi-	Barks	Decoction	General malaise, severe cough, fever and headache, and	N/A	[65]

friderici

as an emetic

Barks Pulp Relieve costal and side pains of chest Democratic republic

of Congo

[65]

Barks, fruits, and leaves

N/A Tuberculosis, severe cough, headache, fever, and sore eyes

Cameroon [49]

Fruits N/A Tuberculosis Democratic republic of Congo

[65]

Leaves Decoction Sore eyes N/A [65]

Roots N/A Sexual impotence Ghana [66]

C. africana Bark and roots Dry powder Cancer South Africa [16]

Infused in water or milk

Ground Bark	N/A	General pain, headache, and fever	Nigeria	[15]
Leaves	Direct Consumption	Trypanosomiasis edema (Cattle)	Kenya	[14]
Leaves	Pounded leaves	Indigestion (Cattle)	Mali	[14]
Leaves	N/A	Pleurisy	Lesotho	[15]
Leaves	N/A	Indigestion, edema	South Africa	[67]
N/A	N/A	Rheumatism, pains, syphilis, cancer	South Africa	[17,18]
Bark	Decoction	Astringent for peptic ulcers, dysentery, and diarrhea	India	[23]
Barks	Paste	Bones, pimples, contusions, sprains and joint pains	India	[19]
Fruits	N/A	Amenorrhea, colic, heavy menstrual and intermenstrual	India	[20,21]

C. australis

bleeding

Leaves and fruits Decoction Peptic ulcers, dysentery, diarrhea, heavy menstrual and

intermenstrual bleeding, and amenorrhea

India [19]

Roots Boiling Colic and other stomach troubles India [23,24] Stems & Leaves Crushing Leprosy India [22]

N/A N/A Gastrointestinal problems Morocco [25]

C. choseniana Leaves N/A Inflammation exposure Korean [68]

C. ehrenbergiana Leaves Infusion Indigestion N/A [69]

C. eriocarpa Bark Grounded powder Sprain, pimples and India [70]

Joint pain

Barks Powdered bark Tumor, scabies and skin problems Kashmir [71] Seeds Dry seeds Dysentery Kashmir [71]

Fruits N/A Amenorrhea and colic India [72]

Leaves Decoction Amenorrhea Pakistan [73]

C. iguanaea Bark N/A Fever Brazil [74] Fruits Decoction Dysentery and intestinal catarrh Brazil [75]

Fruits Sap Eye diseases N/A [76] Leaves Infusion Used as a vaginal douche to treat leucorrhea Brazil [75] Leaves and fruits Aqueous infusion Kidney pain Ecuador [77]

Leaves and flowers

Infusion Diabetes mellitus Mexico [78]

Leaves and roots Decoction Urinary tract infections Brazil [79]

N/A Use as tea Body aches, rheumatism, chest pain, asthma, cramps,

poor digestion, diuretics

Brazil [80]

C. laevigata Barks Boiling liquor Sore throats America [81] Barks Powdered shells Venereal diseases America [81]

C. occidentalis Barks Decoction Menses and sore throat America [81]

Barks Decoction &

powdered shells

Venereal Diseases America [81]

Wood

Extracts

Jaundice Canada [26]

C. pallida Stems and Leaves

Dry Powder Stomach aches, diarrhea, inflammation, wounds,

cholera, pain, coughing, and skin infections

Mexico [36]

C. philippensis Leaves Saps Parasitic infections N/A [82] Roots N/A Ulcer Tanzania [83]

C. sinensis Barks Decoction Lumbago, menstruation irregularity, gastric problems,

abdominal pain

Korea [84]

Leaves Decoction, paste Lacquer sore, urticaria, eczema Korea [84]

Root barks N/A Dyspepsia, poor appetite, shortness of breath, and swollen feet

China [21]

C. tessmannii Bark Decoction Diabetes and hypertension problem Cameroon [85] Stem bark Decoction Diabetes mellitus Gabon [86]

N/A Malaria, gangrene, sexual weakness, insomnia, and nervosity

N/A Tachycardia, anemia, respiratory inflammation, analgesics, fever, and diarrhea

Cameroon [85]

Cameroon [85] (continued on next page)

Table 2 (continued )

preparation

Species	Part used	Method of	Medicinal uses	Region	References
C. tetrandra	Excluding root,	N/A	Used as a contraceptive for semen	N/A	[87]

plants coagulation properties

Seeds Juice Indigestion Nepal [88]

Shoots and leaves

N/A Loss of appetite N/A [82]

Roots N/A Laxative N/A [82]

Tender leaves Vegetables Reducing postpartum pains India [89]

C. tournefortii Seeds N/A Kidney sand Turkey [33]

Leaves N/A Stomach pain, cessation of bleeding, inducing sedation, and digestion

Turkey [33]

Fruits N/A Diarrhea, dysentery, and ulcer Turkey [33]

C. zenkeri Stem-bark Decoction Cough, arthritis, fever Nigeria [90–92] Steam-bark Powdered Analgesic Nigeria [90–92]

Wood Macerated Cuts on the skin Nigeria [92]

1. Study on flora and distribution

Celtis plants have axillary spines and can be evergreen or deciduous, polygamo-monoecious, or monoecious. The leaves are alternate and have a whole or toothed margin and three veins from the base. Inflorescences might be clustered into cymelets, racemes, or paniculates. Flowers are small, and either unisexual or bisexual. The inflorescences are made up of branched racemes or panicles.

Flowers are 4–5 merous, with basally slightly connate tepals in male flowers, caducous, and sessile ovaries. The fruit is fleshy with a

wild, foliaceous, and variably folded seed leaf that ranges in size from 3 to 25 mm [45]. Characteristics of flowers, fruits, leaves and distribution of the Celtis plants are given in Table 1.

Ethnopharmacology

Celtis species are being used to treat a variety of diseases almost all around the world. Approximately all parts of Celtis plants are traditionally used to treat various ailments. These parts are processed as decoctions, powdered shells, extracts, and boiling liquor for medicinal purposes (Table 2).

Almost all investigated Celtis species are used to treat pains, sore throats, fevers, diarrhea, and stomach problems (Table 2). The stems and leaves of C. australis and C. pallida, as well as the leaves of C. philippensis, are applied in various forms to treat skin-related problems [36,82,93]. Furthermore, venereal diseases such as sexually transmitted diseases and sexual weakness are treated with

C. africana and the barks of C. occidentalis in the forms of decoction and powdered shells [81,94]. Decoctions of the barks of

C. occidentalis and fruits of C. australis are used to treat menstrual problems such as menses, amenorrhea, heavy menstrual, and intermenstrual bleeding [20,21,81]. The dried barks and roots of C. africana are applied in powder form and infused in water or milk to treat cancer [16]. In Cameroon, the barks, fruits, and leaves of C. adolphi-friderici are used to treat tuberculosis, sore eyes, fever, cough,

and headaches [49]. Another species, C. ehrenbergiana leaves’ infusion is used to treat indigestion [69]. Additionally, the leaves and

fruits of C. iguanaea and the seeds of C. tournefortii are also used to make aqueous infusions for treating kidney problems such as pain and sand [33,77]. These traditional uses suggested that Celtis plants may contain compounds with a wide range of biological activities such as analgesic, antimicrobial, anti-inflammatory, anticancer, antioxidant (protective), anti-fibrinolytic, and anti-diarrhea.

Phytochemistry

Among the numerous species of Celtis plant, only a few have been studied for their phytoconstituents. Although phytochemicals can be found in various parts of the plant, they are mainly found in three principal segments: leaves, stems, and roots. The percentage composition of every plant varies based on preparation techniques, ecological factors, and variety [95]. Flavonoids, tannins, alkaloids, and phenolic constituents are the most common molecules found in phytochemical investigations [96]. Other compounds such as terpenoids, fatty acids, esters, aldehydes, alcohols, and their glycosides are also reported to be present in these plants (Table 3).

Diverse phytochemicals are found in the aerial parts, fruits, leaves, stems, barks, roots, seeds, and twigs of these plants. A study in Saudi Arabia identified amide, fatty acids, terpenoids, sterol [102], and flavonoids [123]in the aerial parts of C. africana, while al- cohols, aldehydes, ketones, and esters were found in the leaves, fruits, and stems in a South African study in addition to fatty acids, terpenoids, and sterol [27].

C. australis leaves, fruits, barks, and stems contain phytochemical elements that are substantially similar to those found in

C. africana, such as phenolic acids, fatty acids, flavonoids, terpenoids, and sterols [31,32,111,122,127]. The ripe fruits and seeds of

C. australis contain various types of esters, and fatty acids [31,32], while the fruits of C. tournefortii contain phenolic acid, benzoic acid, fatty acids, esters, tannins, terpenoids, and flavonoids [33,113,114]. C. pallida possess alcohol, fatty acids, esters, terpenoids, sugars [36], phenolic acids, and flavonoids [117].

In a Hungarian study of dried extract of C. occidentalis, amides were identified in the twigs [100], while an Egyptian study of ethanol extract identified several flavonoid compounds [122]. Dichloromethane-ethanol extracts of C. iguanaea leaves contain

Table 3

Phytochemistry of Celtis genus.

Compound	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
Number							site

Amides

Ceramide Celtisamide A C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS
Ceramide Celtisamide B C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

Cameroon [97]

Fatty acid derivatives Oleamide C. sinensis Leaves and stems

SFE-CO₂ GC-MS China [98]

C. zenkeri Leaves GC-MS Nigeria [99]

Hydroxycinnamic acid derivatives

2-trans-3-(4-hydroxyphenyl)- N-[2-(4- hydroxyphenyl)-2- oxoethyl] prop-2-enamide

C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS, H-NMR, C-NMR,

Hungary [100]

Hydroxycinnamic acid derivatives
Hydroxycinnamic acid derivatives
Hydroxycinnamic acid derivatives

cis-N-coumaroyltyramine C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT-

IR, UV

trans-N-caffeoyltyramine C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR,

EIMS, HREIMS

C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS, H-NMR, C-NMR,

C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT- IR, UV

C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

trans-N-coumaroyloctopamine C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS,

H-NMR, C-NMR,

C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

Korea [101]

Saudi Arabia [102]

Hungary [100]

Korea [101]

Cameroon [97]

Hungary [100]

Cameroon [97]

Hydroxycinnamic acid derivatives

trans-N-coumaroyltyramine C. adolphi- friderici

Roots Acetone extract Cameroon [103]

C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR,

EIMS, HREIMS

C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS, H-NMR, C-NMR,

C. sinensis Twigs Methanol extract EI-MS, H-NMR, C- NMR

C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

C. zenkeri Stem barks Methanol extract HREIMS, C-NMR, H- NMR

Saudi Arabia [102]

Hungary [100]

Korea [104]

Cameroon [97]

[90]

Hydroxycinnamic acid derivatives

trans-N-feruloyloctopamine C. adolphi- friderici

Roots Acetone extract Cameroon [103]

C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS, H-NMR, C-NMR,

C. tessmannii Roots Methanol extract NMR, UV, IR, MS, GC-MS

Hungary [100]

Cameroon [97]

Hydroxycinnamic acid derivatives

trans-N-feruloyltyramine C. adolphi- friderici

Roots Acetone extract Cameroon [103]

C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR,

M.A. Samadd et al.

Heliyon 10 (2024) e29707

EIMS, HREIMS

C. occidentalis Twigs Methanol extract UHPLC-Orbitrap-MS, H-NMR, C-NMR,

Saudi Arabia [102]

Hungary [100] (continued on next page)

Table 3 (continued )

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
11.	Iso-benzo-furanone	Zenkeramide	C. tessmannii C. zenkeri	Roots Stem-barks	Methanol extract Methanol	NMR, UV, IR, MS, H-NMR, C-NMR,	Cameroon Nigeria	[97] [90]
Esters 12.	propanamide Anthraquinone ester	6-hydroxy-5,7,8-trimethoxy-9,10-dioxo-9,10-	C. australis	Stem barks	Ethanol extract	HREIMS H-NMR, C-NMR, IR,	India	[105]
13.	Carboxylic ester	dihydroanthracen-2-yl acetate 2-Propenoic acid, butyl ester	C. sinensis	& Fruits Leaves and	SFE-CO₂	MS GC-MS	China	[98]
14. Carboxylic ester		Benzyl benzoate	C. africana	stems Stems	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
15. Carboxylic ester		Malic acid, 4-ethyl ester	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
16. Carboxylic ester		Methyl salicylate	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
17. Ester		Sulfurous acid, dibutyl ester	C. africana	stems Leaves	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
18. Fatty acid ester		1,2-Benzenedicarboxylic acid, butyl oxtyl ester	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
19. Fatty acid ester		2-Methylstearoate	C. australis	stems Ripe Fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
20. Fatty acid ester		Acetic acid n-octadcyl ester	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
21.	Fatty acid ester	Arachidic acid methyl ester	C. tourneforti	stems Leaves and	Hexane extract	GC-MS	Iraq	[106]
22.	Fatty acid ester	Capric acid methyl ester	C. tourneforti	fruits Leaves and	Hexane extract	GC-MS	Iraq	[106]
23.	Fatty acid ester	Dibutyl phthalate	C. sinensis	fruits Leaves and	SFE-CO₂	GC-MS	China	[98]
24.	Fatty acid ester	Diethyl phthalate	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
25. Fatty acid ester		Ethyl linolenate	C. pallida	stems Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
26. Fatty acid ester		Ethyl palmitate	C. africana	Leaves	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
27. Fatty acid ester		Glycerol 1-stearate	C. adolphi-	Roots	Acetone extract	FAB-MS, EI-MS, H-	Cameroon	[103]
28.	Fatty acid ester	Hexadecanoic, 2-hydroxyethyl ester	friderici C. pallida C. sinensis	Aerial parts Leaves and	Ethanol extract SFE-CO₂	NMR GC-MS GC-MS	Mexico China	[36] [98]
29. Fatty acid ester		Hexacosyl heptafluorobutyrate	C. zenkeri	stems Leaves	Methanol	GC-MS	Nigeria	[107]
30. Fatty acid ester		Lignoceric acid methyl ester	C. tourneforti	Leaves and	Hexane extract	GC-MS	Iraq	[106]
31.	Fatty acid ester	Linoleic acid-, 2-hydroxy-1-(hydroxymethyl)	C. africana	fruits Fruits	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
		ethyl ester
32. Fatty acid ester		Linolenic acid, methyl ester	C. africana	Fruits	Ethyl acetate Extract	2D-GC-TOF/MS	South Africa	[27]
33. Fatty acid ester		Methyl 13-methyltetradecanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
34. Fatty acid ester		Methyl 14-acetyl hydroxy palmitate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
35. Fatty acid ester		Methyl 1-dotriacontanoate	C. australis	Ripe Fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
36. Fatty acid ester		Methyl 1-tetradecanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
37. Fatty acid ester		Methyl 2,4-dimethyl heneicosanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
38. Fatty acid ester		Methyl dotriacentanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
39. Fatty acid ester		Methyl linoleate	C. australis	Ripe Fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
40. Fatty acid ester		Methyl oleate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
			C. zenkeri	Leaves		GC-MS	Nigeria	[31]

site

GC-MS

(continued on next page)

Table 3 (continued )

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
41.	Fatty acid ester	Methyl Palmitate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
			C. iguanaea	Leaves	Dichloromethane and ethanol	GC-MS	Brazil	[108]
42. Fatty acid ester		Methyl pentachloro stearate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
43. Fatty acid ester		Methyl stearate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
			C. iguanaea	Leaves	Dichloromethane and ethanol	GC-MS	Brazil	[108]
					extract
44. Fatty acid ester		Methyl tetradecanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
45. Fatty acid ester		Methyl tricosanoate	C. australis	Ripe fruits	Ethanol extract	FT-IR, GC-MS	India	[31]
			C. tourneforti	Leaves and	Hexane extract	GC-MS	Iraq	[106]
				fruits
46. Fatty acid ester		Monolinolenin	C. africana	Fruits	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
47. Fatty acid ester		Phthalic acid, butyl 2-ethylhexyl ester	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
48.	Fatty acid ester	Phthalic acid, butyl tetradecyl ester	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
49.	Fatty acid ester	Phthalic acid, di-isobutyl ester	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
50. Fatty acid ester		Stigmast-5-en-3-ol oleate	C. ehrenbergiana	stems Leaves	Crude methanolic extract	GC-MS	Brazil	[109]
51. Hydroxycinnamic		Chlorogenic acid	C. australis	Fruits	Methanol extract	HPLC	Iran	[110]
	acid ester		C. australis	Leaves		RP-HPLC, UV	Italy	[111]
C. iguanaea				Leaves	70 % ethanol	HPLC	Brazil	[112]
C. tournefortii				Fruits	Methanol extract	HPLC, UV	Turkey	[113]
C. tournefortii				Fruits &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
52.	Phenolic ester	Protocatechuic acid, ethyl ester	C. tournefortii	Leaves Fruits,	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
53.	Triterpene ester	3β-trans-sinapoyloxylup-20(29)-en-28-ol	C. philippinensis	Leaves & Twigs	Methanol extract	FT-IR, HR-FAB-MS,	Indonesia	[115]
54.	Triterpene ester	3β-trans-feruloyloxy-16β-hydroxylup-20(29)-	C. philippinensis	Twigs	Methanol extract	H-NMR, C-NMR FT-IR, HR-FAB-MS,	Indonesia	[115]
Flavonoids 55.	Anthocyanin	ene Cyanidin-3,5-di-O-glucoside	C. australis	fruits &	Water and ethanol extract	H-NMR, C-NMR UHPLC–QqQ-MS/	Croatia	[32]
56.	Anthocyanin	Delphinidin-3,5-di-O-glucoside	C. australis	Leaves fruits &	Water extract	MS, UV UHPLC–QqQ-MS/	Croatia	[32]
57.	Anthocyanin	Pelargonidin-3,5-di-O-glucoside	C. australis	Leaves fruits &	Water and ethanol extracts	MS, UV UHPLC–QqQ-MS/	Croatia	[32]
58.	Flavanol	Afzelechin	C. tetrandra	Leaves Barks	Ethyl acetate extract	MS, UV MS, H-NMR, C-NMR,	Thailand	[116]
59.	Flavanol	Catechin	C. pallida	Leaves &	Methanol, methanol-water or	HRESIMS HPLC	Mexico	[117]
				Fruits	acetone extract
C. tetrandra				Barks	Ethyl acetate extract	MS, H-NMR, C-NMR,	Thailand	[116]
						HRESIMS
C. tournefortii				Fruits	Methanol extract	HPLC, UV	Turkey	[113]
C. tournefortii				Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
				Young twigs

site

extract

Young twigs

(continued on next page)

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

Flavanol Epiafzelechin C. tetrandra Barks Ethyl acetate extract MS, H-NMR, C-NMR,

HRESIMS

Flavanol Epicatechin C. australis Leaves Ethanol extract UHPLC–QqQ-MS/ MS, UV

Thailand [116]

Croatia [32]

C. pallida Leaves &

Fruits

Methanol, methanol-water or acetone extract

HPLC Mexico [117]

Flavanol Gallocatechin C. pallida Leaves Methanol, methanol-water or acetone extract

HPLC Mexico [117]

Flavanol dimer Epiafzelechin-(4α→8)-catechin C. tetrandra Barks Ethyl acetate extract MS, H-NMR, C-NMR,

HRESIMS

Flavanol dimer Epiafzelechin-(4α→8)-epicatechin C. tetrandra Barks Ethyl acetate extract MS, H-NMR, C-NMR,

HRESIMS

Thailand [116]

Flavanone Naringenin C. tournefortii Fruits Water, ethanol and methanol extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Fruits, Leaves & Young twigs

methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavanone glycoside Eriodictyol acetyl-glucoside- pentoside C. eriocarpa leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]
Flavanone glycoside Hesperidin C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavanone glycoside Naringenin glucuronide glucoside C. eriocarpa Leaves methanol extract UHPLC-DAD, ESI-MS Pakistan [118]
Flavanone glycoside Naringin C. tournefortii Fruits Water, ethanol and methanol extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Fruits, Leaves &Young twigs

Flavanone glycoside Neohesperidin C. tournefortii Leaves &

Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavanonol Taxifolin C. tournefortii Fruits Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]
Flavone Acacetin C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]
Flavone Apigenin C. australis Fruits Ethanol extract EIMS, IR, H-NMR, C- NMR

India [119]

C. australis Fruits Methanol extract HPLC Iran [110]

C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey, Iraq [106,

114]

Flavone Diosmetin C. tournefortii Young twigs Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]
Flavone Hispidulin C. australis Leaves Methanol extract LC-MS Montenegreo [120]
Flavone Luteolin C. choseniana Leaves Methanol extract HPLC Korea [68]
Flavone Wogonin C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavone glycoside 2″-O-α-L-rhamnopyranosyl-7-O-methylvitexin C. australis Leaves RP-HPLC, UV Italy [111]
Flavone glycoside 2-O-pentosyl-8-C-hexosyl-apigenin C. iguanaea Leaves Dichloromethane extract ESI-MS Brazil [121]
Flavone glycoside 2″-O-β-D-galactopyranosyl orientin C. australis Leaves Ethanol extract UV, HRESIMS, 1D-

NMR, 2D-NMR

Egypt [122]

(continued on next page)

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Table 3 (continued )

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
81.	Flavone glycoside	2″-O-β-galactopyranosyl vitexin	C. occidentalis C. australis	Leaves Leaves	Ethanol extract Ethanol extract	UV, HRESIMS, 1D- UV, HRESIMS, 1D-	Egypt Egypt	[122] [122]
C. occidentalis				Leaves	Ethanol extract	NMR, 2D-NMR UV, HRESIMS, 1D-	Egypt	[122]
						NMR, 2D-NMR
82. Flavone glycoside		2-α-rhamnopyranosyl vitexin	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
83. Flavone glycoside		4‴-rhamnosyl-2″-O-β-D-galactopyranosyl vitexin	C. australis	Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
C. occidentalis				Leaves	Ethanol extract	NMR, 2D-NMR UV, HRESIMS, 1D-	Egypt	[122]
84. 85.	Flavone glycoside Flavone glycoside	Acacetin 7-O-glucoside Acacetin-8-C-rutinoside	C. australis C. eriocarpa	Leaves Leaves	Methanol extract	NMR, 2D-NMR RP-HPLC, UV UHPLC-DAD, ESI-MS	Italy Pakistan	[111] [118]
86.	Flavone glycoside	Apigenin 6-C-glucoside	C. australis	Leaves		RP-HPLC, UV	Italy	[111]
87. Flavone glycoside		Apigenin 7-O-galloylrhamnoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
88. Flavone glycoside		Apigenin-6,8-di-C-glucoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
89. Flavone glycoside		Apigenin-6,8-di-C-rhamnoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
90. Flavone glycoside		Apigetrin	C. australis	Leaves	Methanol extract	LC-MS	Montenegreo	[120]
			C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
91. Flavone glycoside		Baicalein dipentosidehexoside	C. eriocarpa	Young twigs Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
92. Flavone glycoside		Baicalein-8-C-glucoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
93. Flavone glycoside		Baicalin	C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
94. Flavone glycoside		Celtiside A	C. africana	Young twigs Aerial parts	Ethanol and water extract	1D NMR, 2D NMR	Saudi Arabia	[123]
95. Flavone glycoside		Celtiside B	C. africana	Aerial parts	Ethanol and water extract	1D NMR, 2D NMR	Saudi Arabia	[123]
96. Flavone glycoside		Dihydroluteolin-7-O-glucoronide	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
97. Flavone glycoside		Diosmin	C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
98.	Flavone glycoside	Isoorientin	C. australis	Young twigs Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
C. occidentalis				Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
						NMR, 2D-NMR
99. Flavone glycoside		Isoswertiajaponin	C. africana	Aerial parts	Ethanol and water extract	1D NMR, 2D NMR	Saudi Arabia	[123]
100. Flavone glycoside		Isoswertisin	C. africana	Aerial parts	Ethanol and water extract	1D NMR, 2D NMR	Saudi Arabia	[123]
101.	Flavone glycoside	Isovitexin	C. australis	Leaves		RP-HPLC, UV	Italy	[111]
C. australis				Ethanol extract		UV, HRESIMS, H-	Egypt	[122]
						NMR, C-NMR
C. occidentalis				Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
			C. sinensis	Leaves	Ethanol extract	NMR, 2D-NMR	China	[124]
102. Flavone glycoside		Isovitexinhydroxyferuloyl glucoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
103. Flavone glycoside		Luteolin-4 -O-rhamnosyl (1 → 2) glycoside	C. iguanaea	Leaves	Dichloromethane extract	ESI-MS	Brazil	[121]
104. Flavone glycoside		Luteolin-6-C-acetyl pentoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
105. Flavone glycoside		Orientin	C. africana	Aerial parts	Ethanol and water extract	1D NMR, 2D NMR	Saudi Arabia	[123]
			C. australis	Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
						NMR, 2D-NMR
C. occidentalis				Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
						NMR, 2D-NMR

site

NMR, 2D-NMR

(continued on next page)

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

C. iguanaea Leaves Dichloromethane extract ESI-MS Brazil [121]

106. Flavone glycoside Scutellarin C. tournefortii Fruits, Leaves & Young twigs

107. Flavone glycoside	Tetrahydroxy isoflavone-O-hexoside	C. iguanaea	Leaves	Dichloromethane extract	ESI-MS	Brazil	[121]
108. Flavone glycoside	Vitexin	C. africana	Aerial parts	Ethanol & water extract	1D NMR, 2D NMR	Saudi Arabia	[123]

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. australis Leaves RP-HPLC, UV Italy [111]

C. australis Ethanol extract UV, HRESIMS, 1D- NMR, 2D-NMR

C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
C. iguanaea	Leaves	Dichloromethane extract	ESI-MS	Brazil	[121]
C. occidentalis	Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]
C. africana	Aerial parts	Ethanol and water extract	NMR, 2D-NMR 1D NMR, 2D NMR	Saudi Arabia	[123]
C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]

Egypt [122]

109. Flavone glycoside Vitexin 2″-O-rhamnoside

Young twigs

110.	Flavonol	Fisetin
111.	Flavonol	Galangin
112.	Flavonol	Kaempferol
113.	Flavonol	Morin
114.	Flavonol	Myricetin
115.	Flavonol	Quercetin

C. tournefortii Leaves &

Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. tournefortii Fruits Water, ethanol and methanol

extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Leaves &

Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. choseniana Leaves Methanol extract HPLC Korea [68]

C. tournefortii Fruits Water, ethanol and methanol

extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Leaves &

Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. tournefortii Fruits Methanol extract HPLC, UV Turkey [113]

C. tournefortii Young twigs Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. australis Fruits Ethanol extract EIMS, IR, H-NMR, C- NMR

India [119]

C. choseniana Leaves Methanol extract HPLC Korea [68]

C. ehrenbergiana Leaves Lyophilized aqueous, and crude

methanolic extract

GC-MS Brazil [109]

C. iguanaea Leaves 70 % Ethanol HPLC Brazil [112]

C. tournefortii Fruits Water, ethanol and methanol

extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Leaves &

Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavonol glycoside Isorhamnetin hexosidepentoside C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]
Flavonol glycoside Kaempferol 3-O-glucoside C. australis Leaves Methanol extract LC-MS Montenegreo [120]
Flavonol glycoside Quercetin rhamnosidedipentoside C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]
Flavonol glycoside Quercetin-3-β-D-glucoside C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Flavonol glycoside Rutin C. australis Fruits Methanol extract HPLC Iran [110]

C. australis Leaves Ethanol extract UV, HRESIMS, 1D- NMR, 2D-NMR

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Egypt [122]

(continued on next page)

Table 3 (continued )

site

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
			C. iguanaea	Leaves	70 % Ethanol extract	HPLC	Brazil	[112]
			C. occidentalis	Leaves	Ethanol extract	UV, HRESIMS, 1D-	Egypt	[122]

C. tournefortii Fruits Water, ethanol and methanol

extract

NMR, 2D-NMR

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Fruits Methanol extract HPLC, UV Turkey [113]

C. tournefortii Fruits, Leaves & Young twigs

Methanolic solution with 1 % acetic acid

HPLC Iraq [106]

C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. iguanaea Leaves Dichloromethane extract ESI-MS Brazil [121]

Flavonolignan Silibinin C. tournefortii Young twigs Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]
Isoflavone Biochanin A C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

C. tournefortii Leaves Methanol extract LC-MS/MS Mardin [125]

Isoflavone glycoside Genistin C. iguanaea Leaves Dichloromethane extract ESI-MS Brazil [121]

Organic acids

Aliphatic carboxylic acid

5-hydroxypipecolic acid C. ehrenbergiana Leaves Crude methanolic extract GC-MS Brazil [109]

Aliphatic carboxylic acid

Azelaic acid C. adolphi-

friderici

Roots Acetone extract ESIHRMS, EI-MS, H- NMR

Cameroon [103]

Aliphatic carboxylic acid

Fumaric acid C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Aliphatic carboxylic acid
Aliphatic dicarboxylic acid

Methyl quinic acid C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118] Quinic acid C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]

Aliphatic dicarboxylic acid

Sebacic acid C. adolphi-

friderici

Roots Acetone extract EI-MS, H-NMR Cameroon [103]

Aliphatic dicarboxylic acid

Shikimic Acid C. tournefortii Leaves Methanol extract LC-MS/MS Mardin [125]

Aliphatic dicarboxylic acid

Succinic acid C. tessmannii Roots Methanol extract NMR, UV, IR, MS, GC-MS

Cameroon [97]

Benzoic acid

4-Hydroxybenzoic acid C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Benzoic acid

Hydroxybenzoic acid C. adolphi- friderici

Roots Acetone extract Cameroon [103]

135. Dicarboxylic acid	Tartaric acid quinylhydroxybenzoylglucoronide	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
136. Dihydroxy-benzoic	Gentisic acid	C. laevigata	Leaves	Aqueous extract	UV,	United States	[126]

Carboxylic acid metabolites

Allantoin C. adolphi-

friderici

Roots Acetone extract Cameroon [103]

acid

M.A. Samadd et al.

Heliyon 10 (2024) e29707

C. tournefortii Fruits, Leaves &

Chromatographed

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

(continued on next page)

Table 3 (continued )

site

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
137.	Dihydroxy-benzoic	Protocatechuic acid	C. tournefortii	Young twigs	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
138.	acid Dihydroxy-benzoic	Vanillic acid	C. australis C. australis	Leaves Leaves	Methanol extract Ethanol extracts	LC-MS UHPLC–QqQ-MS/	Montenegreo Croatia	[120] [32]
acid C. australis				Leaves	Hydro-methanolic extract	MS, UV H-NMR, C-NMR,	Morocco	[127]
C. adolphi-				Roots	Acetone extract	H-NMR, C-NMR,	Cameroon	[103]
			friderici
C. tournefortii				Fruits	Water, ethanol and methanol	RP-HPLC-DAD, UV	Turkey	[33]
					extract
C. tournefortii				Fruits,	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
				Leaves &
139.	Fatty acid	2-hydroxy linoleic acid	C. eriocarpa	Young twigs Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
140.	Fatty acid	Behenic acid	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
141.	Fatty acid	Heptacosanoic acid	C. adolphi-	Roots	Acetone extract	EI-MS, H-NMR	Cameroon	[103]
142.	Fatty acid	Hexacosanoic acid	friderici C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
143.	Fatty acid	Hydroxy linolenic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
144. 145.	Fatty acid Fatty acid	Lacceroic acid Lauric acid	C. adolphi- friderici C. africana	Roots Aerial parts	Acetone extract Ethanol-water extract	EIHRMS, EI-MS, H- H-NMR, C-NMR,	Cameroon Saudi Arabia	[103] [102]
146.	Fatty acid	Lignoceric acid	C. pallida	Aerial parts	Ethanol extract	EIMS, HREIMS GC-MS	Mexico	[36]
147.	Fatty acid	Linoleic acid	C. africana	Leaves,	Hexane extract, Ethyl acetate	2D-GC-TOF/MS	South Africa	[27]
				Fruits & Stems	extract, Dichloromethane:
C. australis				Seeds	Water and ethanol extracts	UHPLC–QqQ-MS/	Croatia	[32]
C. pallida				Aerial parts	Ethanol extract	MS, UV GC-MS	Mexico	[36]
C. tournefortii				Fruits	Water, ethanol and methanol	GC, FID	Turkey	[33]
148.	Fatty acid	Linolenic acid	C. africana	Fruits,	extract Hexane extract, Ethyl acetate	2D-GC-TOF/MS	South Africa	[27]
				Leaves &	extract, dichloromethane: methanol

NMR

methanol extract

Stems extract

C. ehrenbergiana Leaves Crude methanolic extract GC-MS Brazil [109]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

C. tournefortii Fruits Water, ethanol and methanol

extract

149.	Fatty acid	Margaric acid	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
150.	Fatty acid	Myristic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
151.	Fatty acid	Nonadecanoic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
152.	Fatty acid	Octacosanoic acid	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
153.	Fatty acid	Oleic acid	C. africana	Aerial parts	Ethanol-water extract	H-NMR, C-NMR,	Saudi Arabia	[102]
C. australis				Seeds	Water and ethanol extracts	UHPLC–QqQ-MS/	Croatia	[32]
C. tournefortii				Fruits	Water, ethanol and methanol	MS, UV GC, FID	Turkey	[33]
					extract

GC, FID Turkey [33]

M.A. Samadd et al.

Heliyon 10 (2024) e29707

EIMS, HREIMS

(continued on next page)

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

Fatty acid Palmitic acid C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR, EIMS, HREIMS

Saudi Arabia [102]

C. africana Leaves, Fruits & Stems

Hexane extract, Ethyl acetate extract, Dichloromethane: methanol extract

2D-GC-TOF/MS South Africa [27]

C. australis Seeds Water and ethanol extracts UHPLC–QqQ-MS/

MS, UV

Croatia [32]

C. ehrenbergiana Leaves Crude methanolic extract GC-MS Brazil [109]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

C. sinensis Leave &

Stems

SFE-CO₂ GC-MS China [98]

C. tournefortii Fruits Water, ethanol and methanol

extract

Fatty acid Palmitoleic acid C. tournefortii Fruits Water, ethanol and methanol extract

GC, FID Turkey [33]

Fatty acid Stearic acid C. australis Seeds Water and ethanol extracts UHPLC–QqQ-MS/

MS, UV

Croatia [32]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

C. sinensis Leaves and stems

SFE-CO₂ GC-MS China [98]

C. tournefortii Fruits Water, ethanol and methanol

extract

GC, FID Turkey [33])

Hydroxycinnamic acid Hydroxycinnamic acid Hydroxycinnamic

Aesculetin C. australis Leaves Methanol extract LC-MS Montenegreo [120] Benzoyl sinapic acid C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]

Caffeic acid C. australis Fruits Methanol extract HPLC Iran [110]

acid

C. laevigata Leaves Aqueous extract UV, Chromatographed

United states [126]

C. pallida Fruits Methanol, methanol-water or

acetone extract

C. tournefortii Fruits Water, ethanol and methanol

extract

HPLC Mexico [117]

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Fruits Methanol extract HPLC, UV Turkey [113]

C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Hydroxycinnamic

Cinnamic acid C. australis Fruits Methanol extract HPLC Iran [110]

acid

C. pallida Fruits Methanol, methanol-water or

acetone extract

C. tournefortii Leaves Methanol solution with 1 % acetic

acid

HPLC Mexico [117]

HPLC Turkey [106]

Hydroxycinnamic acid Hydroxycinnamic

Hydroxy-caffeic acid C. eriocarpa Leaves Methanol extract UHPLC-DAD, ESI-MS Pakistan [118]

p-coumaric acid C. australis Fruits Methanol extract HPLC Iran [110]

acid

C. laevigata Leaves Aqueous extract UV, Chromatographed

United states [126]

C. tournefortii Fruits Methanol extract HPLC, UV Turkey [113]

M.A. Samadd et al.

Heliyon 10 (2024) e29707

(continued on next page)

Table 3 (continued )

site

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
			C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
163. 164.	Hydroxycinnamic acid Hydroxycinnamic	p-Coumaric acid-O-glucoside Phenyl caffeic acid	C. eriocarpa C. eriocarpa C. eriocarpa	Young twigs Leaves Leaves Leaves	Methanol extract Methanol extract Methanol extract	UHPLC-DAD, ESI-MS UHPLC-DAD, ESI-MS UHPLC-DAD, ESI-MS	Pakistan Pakistan Pakistan	[118] [118] [118]
165.	acid Hydroxycinnamic	Sinapic acid	C. tournefortii	Leaves &	Methanol–dichloromethane extract	HPLC-TOF/MS	Turkey	[114]
166.	acid Hydroxycinnamic acid glycoside	Rosmarinic acid	C. tournefortii	Young twigs Fruits	Water, ethanol and methanol	RP-HPLC-DAD, UV	Turkey	[33]
167. Phenolic acid		Dehydro-acacetin dihydroxybenzoic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
168. Phenolic acid		Quinic acid phenol	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
169. Phenolic acid		Quinoyl galloyl tartaric acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
170. Phenolic acid		Quinyl malic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
171. Phenolic acid		Quinylvanilyl malic acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
172. Phenolic acid		Syringic acid quinylrhamnoside	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
173. Trihydroxy- benzoic		Gallic acid	C. australis	Fruits &	Water extract	UHPLC–QqQ-MS/	Croatia	[32]
acid C. australis				leaves Fruits	Methanol extract	MS, UV HPLC	Iran	[110]
C. ehrenbergiana					Lyophilized aqueous and crude	GC-MS	Brazil	[109]
					methanolic extract
C. iguanaea				Leaves	70 % Ethanol	HPLC	Brazil	[112]
C. pallida				Leaves &	Methanol, methanol-water or	HPLC	Mexico	[117]

extract

Terpenoids

174.	Bacterial pentacyclic	3β-hydroxy-35-(cyclohexyl-50-propan-70-one)-	C. australis	Barks	Ethanol extract	IR, 2D NMR, ESI-MS,	India	[128]
175.	triterpenoid Carotenoid	33-ethyl-34-methylbactereohopane Lutein	C. australis	Fruits	Water and ethanol extracts	n LCMS QTOF UHPLC–QqQ-MS/	Croatia	[32]
176.	Carotenoid	Zeaxanthin	C. australis	Fruits	Water and ethanol extracts	MS, UV UHPLC–QqQ-MS/	Croatia	[32]
177.	Carotenoid	β-carotene	C. australis	Fruits	Water and ethanol extracts	MS, UV UHPLC–QqQ-MS/	Croatia	[32]
178.	Diterpene	Phytol	C. africana	Leaves	Ethyl acetate extract,	MS, UV 2D-GC-TOF/MS	South Africa	[27]
C. iguanaea				Leaves	Dichloromethane: methanol extract Dichloromethane and ethanol	GC-MS	Brazil	[108]
C. pallida				Aerial parts	extract Ethanol extract	GC-MS	Mexico	[36]
C. zenkeri				Leaves,		GC-MS	Nigeria	[99]
179.	Diterpene	Retinol	C. tournefortii	Stem-bark Fruits	Water, ethanol and methanol	RP-HPLC-DAD, UV	Turkey	[33]
180.	Tocopherol	ç-Tocopherol	C. africana	Leaves	extract Hexane extract	2D-GC-TOF/MS	South Africa	[27]
181.	Tocopherol	α-Tocopherol	C. africana	Stems & Leaves	Ethyl acetate extract,	2D-GC-TOF/MS	South Africa	[27]

Fruits

C. tournefortii Fruits, Leaves, & Young twigs

acetone extract

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Dichloromethane: methanol extract

(continued on next page)

Table 3 (continued )

site

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
			C. australis	Fruits	Water and ethanol extracts	UHPLC–QqQ-MS/	Croatia	[32]

MS, UV

C. ehrenbergiana Leaves Crude methanolic extract GC /MS Brazil [109]

C. tournefortii Fruits Water, ethanol and methanol

extract

RP-HPLC-DAD, UV Turkey [33]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

Tocopherol γ-tocopherol C. australis Fruits Water and ethanol extracts UHPLC–QqQ-MS/ MS, UV
Tocopherol δ-tocopherol C. australis Fruits Water and ethanol extracts UHPLC–QqQ-MS/ MS, UV

Croatia [32]

C. tournefortii Fruits Water, ethanol and methanol

extract

RP-HPLC-DAD, UV Turkey [33]

Triterpenoid (3β)-3-hydroxy-30-propylhopan-31-one

C. australis Stem barks

& Fruits

Ethanol extract H-NMR, C-NMR, IR, MS

India [105]

Triterpenoid (3β)-oleanan-3-ol C. australis Stem barks

& Fruits

Triterpenoid (9β,31R)-9,25-cyclo-30-propylhopan-31-ol C. australis Stem barks

& Fruits

Ethanol extract H-NMR, C-NMR, IR, MS

India [105]

Triterpenoid 20-epibryonolic acid C. philippinensis Twigs Methanol extract FT-IR, HR-FAB-MS,

H-NMR, C-NMR

Triterpenoid 3β-O-(E)-coumaroylbetulin C. philippinensis Twigs Methanol extract FT-IR, HR-FAB-MS,

H-NMR, C-NMR

Triterpenoid 3β-O-(E)-feruloylbetulin C. philippinensis Twigs Methanol extract FT-IR, HR-FAB-MS,

H-NMR, C-NMR

Triterpenoid Betulin C. philippinensis Twigs Methanol extract FT-IR, HR-FAB-MS, H-NMR, C-NMR
Triterpenoid Betulinic acid C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

Indonesia [115]

Cameroon [97]

Triterpenoid Epifriedelanol C. iguanaea Barks Ethanol extract H-NMR, C-NMR Brazil [129]

C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT- IR, UV,

Korea [101]

Triterpenoid Friedelin C. adolphi- friderici

Roots Acetone extract Cameroon [103]

C. africana Stems Ethyl acetate extract,

Dichloromethane: methanol extract

2D-GC-TOF/MS South Africa [27]

C. iguanaea Barks Ethanol extract H-NMR, C-NMR Brazil [129]

C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

Cameroon [97]

Triterpenoid Friedelinol C. africana Stems Hexane extract, Ethyl acetate extract, Dichloromethane: methanol extract

2D-GC-TOF/MS South Africa [27]

Triterpenoid Germanicol C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT- IR, UV,
Triterpenoid Lupeol C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR, EIMS, HREIMS

Korea [101]

Saudi Arabia [102]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

Triterpenoid Oleanolic acid C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR,

M.A. Samadd et al.

Heliyon 10 (2024) e29707

EIMS, HREIMS

Saudi Arabia [102] (continued on next page)

Table 3 (continued )

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
198.	Triterpenoid	Platanic acid	C. tessmannii C. tessmannii	Stem barks Stem barks	Methanol extract Methanol extract	NMR, UV, IR, MS, NMR, UV, IR, MS,	Cameroon Cameroon	[97] [97]
199.	Triterpenoid	Squalene	C. africana	Leaves	Dichloromethane: methanol extract	GC-MS 2D-GC-TOF/MS	South Africa	[27]
200.	Triterpenoid	Ursolic acid	C. ehrenbergiana C. pallida C. pallida	Aerial parts Aerial parts	Crude methanolic extract Ethanol extract Ethanol extract	GC-MS GC-MS GC-MS	Brazil Mexico Mexico	[109] [36] [36]
			C. philippinensis	Twigs	Methanol extract	FT-IR, HR-FAB-MS,	Indonesia	[115]
C. tessmannii				Stem barks	Methanol extract	NMR, UV, IR, MS,	Cameroon	[97]
201.	Triterpenoid	(3β,9β)-9,25-cycloolean-12-en-3-yl β-D-	C. australis	Stem barks	Ethanol extract	GC-MS H-NMR, C-NMR, IR,	India	[105]
	glycoside	glucofuranoside		& Fruits		MS
Miscellaneous compounds 202. Acid anhydrate		2-Dodecen-1-yl (—) succinic anhydride	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
203. Acid anhydrate		Hydroxy-benzoyl p-coumaric acid anhydride	C. tessmannii	Roots	Methanol extract	NMR, UV, IR, MS,	Cameroon	[97]
204.	Alcohol	1,2-Epoxylinalool	C. sinensis	Leaves and	SFE-CO₂	GC-MS GC-MS	China	[98]
205.	Alcohol	1-Eicosanol	C. africana	stems Leaves	Ethyl acetate extract	2D-GC-TOF/MS	South Africa	[27]
206.	Alcohol	1-Hexacosanol	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
207.	Alcohol	1-Hexadecanol	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
208.	Alcohol	1-Propanol, 2-(dimethyl-amino)-2-methyl	C. africana	stems Fruits	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
209.	Alcohol	1-Tetracosanol	C. pallida	Aerial parts	Ethanol extract	GC-MS	Mexico	[36]
210.	Alcohol	2,2,3,4-Tetramethylhex-5-en-3-ol	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
211.	Alcohol	2-Ethyl-1-hexanol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
212.	Alcohol	2-Hexen-1-ol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
213.	Alcohol	2-Methyl-1-hexadecanol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
214.	Alcohol	3,4,4-Trimethyl-3-pentanol	C. africana	stems Fruits	Ethyl acetate extract	2D-GC-TOF/MS	South Africa	[27]
215.	Alcohol	3,7,11,15-Tetramethyl-2-hexadecen-1-ol	C. iguanaea	Leaves	Dichloromethane and ethanol	GC-MS	Brazil	[108]
216.	Alcohol	3,7-Dimethyl-2,6-octadien-1-ol	C. sinensis	Leaves and	extract SFE-CO₂	GC-MS	China	[98]
217.	Alcohol	3-Hexanol,4,4-dimethyl-	C. africana	stems Leaves	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
218.	Alcohol	3-Hexen-1-ol	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
219.	Alcohol	Docosanol	C. africana C. pallida	stems Leaves Aerial parts	Hexane extract Ethanol extract	2D-GC-TOF/MS GC-MS	South Africa Mexico	[27] [36]
220.	Alcohol	Mome inositol	C. africana	Leaves,	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
				Fruits &
				Stems

site

GC-MS

H-NMR, C-NMR

stems

(continued on next page)

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

Alcohol ND2H-1-Benzopyran-6-ol,3,4-dihydro-2,7,8- trimethyl- 2-(4,8,12-trimethyltridecyl)

C. africana Fruits Ethyl acetate extracts 2D-GC-TOF/MS South Africa [27]

Alcohol n-Tridecan-1-ol C. africana Stems Ethyl acetate extract 2D-GC-TOF/MS South Africa [27]
Alcohol Sapiol C. adolphi- friderici

Roots Acetone extract NMR and MS Cameroon [103]

Alcohol trans-9-Hexadecen-1-ol C. sinensis Leaves and Stems
Aldehyde 14-Hexadecenal C. sinensis Leaves and Stems

SFE-CO₂ GC-MS China [98]

Aldehyde 2,4-Heptadienal C. africana Stems Ethyl acetate extract 2D-GC-TOF/MS South Africa [27]
Aldehyde 2-Heptenal C. africana Fruits Dichloromethane: methanol extract 2D-GC-TOF/MS South Africa [27]

C. africana Stems Ethyl acetate extract 2D-GC-TOF/MS South Africa [27]

Aldehyde 2-Propylhexanal C. africana Fruits Hexane extract 2D-GC-TOF/MS South Africa [27]
Aldehyde

3,5-Dihydroxybenzaldehyde

C. australis Fruits &

Leaves

Ethanol extract UHPLC–QqQ-MS/ MS, UV

Croatia [32]

Aldehyde

4-Hydroxybenzaldehyde

C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Aldehyde Benzaldeyde C. sinensis Leaves and Stems
Aldehyde Benzeacetaldehyde C. sinensis Leaves and stems

SFE-CO₂ GC-MS China [98]

Aldehyde Deca-2,4-dienal C. africana Fruits Dichloromethane: methanol extract 2D-GC-TOF/MS South Africa [27]

C. africana Stems Ethyl acetate extract 2D-GC-TOF/MS South Africa [27]

Aldehyde Hexanal C. africana Stems Ethyl acetate extract 2D-GC-TOF/MS South Africa [27]
Aldehyde

Indole-3-carboxaldehyde

C. adolphi- friderici

Roots Acetone extract Cameroon [103]

Alkane (—)-trans-Pinane C. zenkeri Leaves Methanol GC-MS Nigeria [107]
Alkane (R)-1-Methyl-4-(1-methylethyl)-cyclohexene C. sinensis Leaves and

stems

Alkane 1-Docosene C. sinensis Leaves and stems
Alkane 1α,2α,4α-1, 2,4-Trimethyl-cyclohexane C. sinensis Leaves and

stems

Alkane 2,6,10,15-Tetramethyl-heptadecane C. sinensis Leaves and

stems

Alkane 2,6,10-trimethyl-tetradecane C. sinensis Leaves and

stems

Alkane 6-Tridecene C. sinensis Leaves and stems
Alkane 7-Tetradecene C. sinensis Leaves and stems
Alkane Benzedrex C. sinensis Leaves and stems
Alkane bicyclohexane C. sinensis Leaves and stems
Alkane cis-1,2-Dimethyl-cyclohexane C. sinensis Leaves and

stems

SFE-CO₂ GC-MS China [98]

(continued on next page)

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

Alkane cis-1-Ethyl-2-methyl-cyclohexane C. sinensis Leaves and

stems

Alkane Decane C. sinensis Leaves and stems
Alkane Dodecane C. sinensis Leaves and stems
Alkane Ethyl-cyclohexane C. sinensis Leaves and stems
Alkane Heptadecane C. sinensis Leaves and stems
Alkane Hexadecane C. sinensis Leaves and stems
Alkane Nonadecane C. sinensis Leaves and stems
Alkane Nonane C. sinensis Leaves and stems
Alkane Octadecane C. sinensis Leaves and stems
Alkane Pentyl-cyclohexane C. sinensis Leaves and stems
Alkane Tetradecane C. sinensis Leaves and stems

SFE-CO₂ GC-MS China [98]

Alkene 2,4-Dimethylpenta-1,3-diene C. zenkeri Leaves GC-MS Nigeria [99]
Alkene 3,5-Dimethyl-1,6-heptadiene C. zenkeri Leaves GC-MS Nigeria [99]
Alkene Nonadecene C. zenkeri Stem bark GC-MS Nigeria [99]
Amino acid 2-Aminooctanoic acid C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]
Amino acid Aspartic acid C. adolphi- friderici

Roots Acetone extract EI-MS, H-NMR, C- NMR

Cameroon [103]

Benzene 1,2,4,5-Tetramethyl-benzene C. sinensis Leaves and

stems

Benzene 1,3,5-Trimethyl-benzene C. sinensis Leaves and stems
Benzene 1,3-Diethyl-benzene C. sinensis Leaves and stems
Benzene 1,4-Diethyl-benzene C. sinensis Leaves and stems
Benzene 1-Ethyl-3-methyl-benzene C. sinensis Leaves and stems
Benzene 1-Isocyano-2-methyl-benzene C. sinensis Leaves and

stems

Benzene Ethylbenzene C. sinensis Leaves and stems
Benzene Naphthalene C. sinensis Leaves and stems
Benzene p-Xylene C. sinensis Leaves and stems

SFE-CO₂ GC-MS China [98]

Benzopyrone Scopoletin C. laevigata Leaves Aqueous extract UV, Chromatographed

M.A. Samadd et al.

Heliyon 10 (2024) e29707

United States [126] (continued on next page)

Table 3 (continued )

M.A. Samadd et al.

Heliyon 10 (2024) e29707

Compound Number	Chemical class	Compound	Species	Organs	Extract	Structure elucidation	Collection	Rf no.
273. 274.	Benzopyrone glycoside Dimer	Scopolin Quinic acid-O- Malic acid	C. laevigata C. eriocarpa	Leaves Leaves	Aqueous extract Methanol extract	UV, UHPLC-DAD, ESI-MS	United States Pakistan	[126] [118]
275.	Dimer	Quinic acid-O-tartaric acid	C. eriocarpa	Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
276.	Hydroxy pyrone	3-hydroxy-2-methyl-4H-pyran-4-one	C. africana	Fruits	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
277.	Ketone	2-Pyrrolidinone, 1-methyl-	C. zenkeri	Leaves	Methanol extract	GC-MS	Nigeria	[107]
278.	Ketone	1-(4-hydroxy-3-methoxyphenyl) ethanone	C. africana	Stems	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
279.	Ketone	2,3-Heptanedione	C. africana	Stems &	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
280.	Ketone	2,3-Pentanedione	C. africana	Leaves Fruits,	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
281.	Ketone	3,4-Dimethyldihydrofuran-2,5-dione	C. africana	Leaves & Stems	Hexane extract	2D-GC-TOF/MS	South Africa	[27]
282.	Ketone	3,5,6,7,8,8a-hexahydro-4,8a-dimethyl-6-(1-	C. africana	Stems	Dichloromethane: methanol extract	2D-GC-TOF/MS	South Africa	[27]
283.	Ketone	methylethenyl- 2(1H)naphthalenone 3-Hydroxy-5,6-epoxy-aˆ-ionone	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
284.	Ketone	Cyclohexanone	C. sinensis	stems Leaves and	SFE-CO₂	GC-MC	China	[98]
285.	Ketone	Jasmone	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
286.	Lignan glycoside	Pinoresinol-4-O-glucoside	C. sinensis	stems Twigs	Methanol extract	H-NMR, C-NMR, FT-	Korea	[101]
287.	Lignan glycoside	Pinoresinol-4-O-rutinoside	C. sinensis	Twigs	Methanol extract	IR, UV H-NMR, C-NMR, FT-	Korea	[101]
288.	Lipid	1-O-(β-D-glucopyranosyl) -(2S,3S,4R,5E)-2N-	C. africana	Aerial parts	Ethanol-water extract	IR, UV 2D-NMR, MS	Saudi Arabia	[37]
	(glucosphingolipid)	([2′R,6′E]-2′-hydroxyoctadeca-6′-enoylamino)-
289. 290.	Lipid (glucosphingolipid) Nitrogeneous base	5-pentadecaene-1,3,4-triol Eloundemnoside 2-Amino-9-(3,4-dihydroxy-5-hydroxymethyl-	C. adolphi- friderici C. africana	Roots Leaves,	Acetone extract Dichloromethane: methanol	H-NMR, C-NMR, 2D-GC-TOF/MS	Cameroon South Africa	[103] [27]
		tetrahydrofuran-2-yl)-3,9 dihydro-purin-6-one		Fruits &
291. Nitrogeneous base		2,4(1H,3H)-pyrimidinedione,5-methyl	C. africana	Stems	Dichloromethane: methanol	2D-GC-TOF/MS	South Africa	[27]
292. Phenol		2,2′-Methylenebis[6-(1,1-dimethylethyl)-4-	C. sinensis	Leaves and	SFE-CO₂	GC-MS	China	[98]
293.	Phenol	methyl]-phenol 2,4-bis(1,1-dimethylethyl)-Phenol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
294.	Phenol	2-Methoxy-6-(2-propenyl)-phenol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
295.	Phenol	5-Pentyl-1,3-benzenediol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
296.	Phenol	Butylated hydroxytoluene	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
297.	Phenol	Eugenol	C. sinensis	stems Leaves and	SFE-CO₂	GC-MS	China	[98]
298. Phenolic aldehyde		Ferulaldehyde	C. eriocarpa	stems Leaves	Methanol extract	UHPLC-DAD, ESI-MS	Pakistan	[118]
299. Steroid		(3β,9β,14β)-14-hydroxy-9,19-cyclocholan-3-yl	C. australis	Stem barks	Ethanol extract	H-NMR, C-NMR, IR,	India	[119]
		β-D-glucopyranoside		& Fruits		MS

site

Chromatographed

Stems

HRESIMS, UV, IR

Stems

(continued on next page)

Table 3 (continued )

Compound Number

Chemical class Compound Species Organs

Extract

Structure elucidation Collection

site

Rf no.

Sterol α-Sitosterol C. africana Fruits Dichloromethane: methanol extract 2D-GC-TOF/MS South Africa [27]

C. africana Stems &

Leaves

C. sinensis Leaves and stems

Hexane extract 2D-GC-TOF/MS South Africa [27]

SFE-CO₂ GC-MS China [98]

Sterol β-sitosterol C. adolphi-

friderici

Roots Acetone extract H-NMR, C-NMR, HRESIMS, UV, IR

Cameroon [103]

C. africana Aerial parts Ethanol-water extract H-NMR, C-NMR,

EIMS, HREIMS

Saudi Arabia [102]

C. australis Leaves Hydro-methanolic extract H-NMR, C-NMR, Morocco [127]

C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]

C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT- IR, UV

C. tessmannii Stem barks Methanol extract NMR, UV, IR, MS, GC-MS

C. zenkeri Stem barks Methanol HREIMS, H-NMR, C- NMR

Korea [101]

Cameroon [97]

Nigeria [90]

Sterol Gamma-sitosterol C. ehrenbergiana Leaves Crude methanolic extract GC-MS Brazil [109]

C. iguanaea Leaves Dichloromethane & ethanol extract GC-MS Brazil [108]

Sterol glycoside β-sitosterol-3-O-β-glucoside C. australis Leaves Hydro-methanolic extract H-NMR, C-NMR, Morocco [127]

C. sinensis Twigs Methanol extract H-NMR, C-NMR, FT- IR, UV,

Korea [101]

Sterol glycoside β-sitosterol-3-O-β-D-glucopyranoside C. adolphi-

friderici

Roots Acetone extract Cameroon [103]

C. zenkeri Stem bark Methanol extract HREIMS, H-NMR, C- NMR

Nigeria [90]

Stilbene Resveratrol C. tournefortii Fruits Water, ethanol and methanol extract

RP-HPLC-DAD, UV Turkey [33]

C. tournefortii Leaves Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Stilbenoid glycoside Polydatine C. tournefortii Fruits, Leaves & Young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

Sugar cis-1-O-methylinositol C. tessmannii Roots Methanol extract NMR, UV, IR, MS,

GC-MS

Cameroon [97]

Sugar Sucrose C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]
Sugar D-Turanose C. pallida Aerial parts Ethanol extract GC-MS Mexico [36]
Tannin Glucosyringic acid C. tessmannii Roots Methanol extract NMR, UV, IR, MS,

GC-MS

Cameroon [97]

Tannin Ellagic acid C. iguanaea Leaves 70 % ethanol HPLC Brazil [112]

C. tournefortii Fruits Methanol extract HPLC, UV Turkey [113]

C. tournefortii Leaves &

young twigs

Methanol–dichloromethane extract HPLC-TOF/MS Turkey [114]

M.A. Samadd et al.

Heliyon 10 (2024) e29707

terpenoids, alcohol, esters, and sterol [108] as well as flavonoids [121]. However, only flavonoid compounds were reported in the leaves of C. choseniana [68] and the barks of C. tetrandra [116]. The twigs of C. philippinensis contain several terpenoids and terpenoid esters [115]. Phytochemical analysis of the methanol extract of C. eriocarpa leaves revealed the existence of acid anhydrate, fatty acids, phenolic acids, esters, flavonoids, and glycosides [118]. In addition to phenolic acids, benzopyrone and glycoside were isolated from the leaves of C. laevigata as chief cytotoxic compounds [126]. Amides, terpenoids, sterols, and glycosides are also present in the twigs of

C. sinensis [101]. Furthermore, amides, terpenoids, and sterols were also discovered in the stem bark of C. tessmannii, along with acid anhydrate, tannin, and sugar in the roots [97].

Phytochemicals (primary and secondary metabolites) have been known for their wide range of therapeutic advantages for plants and humans [130]. Plant metabolic reactions such as photosynthesis and respiration are controlled by primary metabolites such as chlorophyll, lipids, carbohydrates, proteins, nucleic acids, and amino acids [95,131,132]. Secondary metabolites include terpenoids, flavonoids, alkaloids, phenols, saponins, tannins, steroids, and glycosides, all of which play critical roles in shielding plants from degradation and boosting plant fragrance, appearance and texture [95,132].

Numerous molecules from these classes have been found and evaluated for pharmacological effects in Celtis plants. Despite the

ample papers on phytochemical analysis among many species of Celtis, the structure identification procedure of molecules from these species needs to be explicitly stated in all articles. The compounds were identified using two dimensional time of flight mass spec- troscopy (2D-GC-TOF/MS), proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), elec-

trospray ionization mass spectrometry (ESI-MS), high-resolution fast atom bombardment mass spectroscopy (HR-FAB-MS), gas chromatrography mass spectrometry (GC-MS), reversed-phase high performance liquid chromatography (RP-HPLC), triple quadrupole mass spectroscopy (QqQ-MS), infrared (IR), reversed-phase high performance liquid chromatography diode-array detection (RP- HPLC-DAD), liquid chromatography mass spectrometry (LC-MS), ultra high-pressure liquid chromatography diode-array detection (UHPLC-DAD), high-resolution electron ionization mass spectrometry (HREIMS), high-resolution electrospray ionization mass spec- trometry (HRESIMS), flame ionization detector (FID), and ultra high-pressure liquid chromatography-orbitrap mass spectrometry (UHPLC-Orbitrap-MS).

1. Amide compounds

Till now, very few amide compounds have been found in Celtis species plants. The majority of them are hydroxycinnamic acid derivatives (compounds 4–10), with only two being ceramides (compounds 1–2) (Table 3) (Fig. 1). Hydroxycinnamic acid derivatives are primarily found in aerial parts, roots, and twigs of Celtis plants, while ceramides are present in the stem barks only. The frequently

reported amides in Celtis species is compound 8, which is obtained from the aerial parts of C. africana [102], roots of C. adolphi-friderici

[103], stem barks of C. zenkeri and C. tessmannii [90,97], and twigs of C. sinensis and C. occidentalis [100,101]. Two new ceramides compounds 1–2 were detected as pure compounds from a methanol extract of C. tessmannii stem barks using NMR, ultra violet spectroscopy (UV), IR, MS, and GC-MS methods [97], while a noble iso-benzo-furanone propenamide (compound 11) was discovered from Central African plant C. zenkeri [90]. Compound 3 is the only fatty acid derivative amide found in this study noted from the supercritical fluid extraction of carbon di-oxide (SFE-CO₂) extraction of C. sinensis leaves and stems and leaves of C. zenkeri [98,99]. All

the amide compounds obtained from the genus Celtis are sketched in Fig. 2.

1. Esters

In addition to organic acids, various ester compounds such as carboxylic esters (compounds 13–16), fatty esters (compounds 18–50), and triterpene esters (compounds 53–54) have been documented from Celtis plants (Table 3). These constituents are mainly identified in leaves, fruits, and stems. Compounds 53 and 54 (triterpene esters) are found for the first time in a methanolic extract of

C. philippinensis twigs through fourier-transform infrared spectroscopy (FT-IR), HR-FAB-MS, H-NMR, and C-NMR techniques [115]. Most isolated esters from the Celtis plants come from a species, but some molecules, including compounds 27, 40, 41, 43, 45, and 51,

have been detected from more than one species (Table 3). Among them, only the compound 51 has been noted in three different species, including C. australis, C. iguanaea, and C. tournefortii [111–113]. Various types of fatty acid esters are reported from the ripe fruits of C. australis via the GC-MS method, where methyl ester of these fatty acids is the most dominating compound (71.60 %) of the total fatty acid composition (95.45 %) [31]. Another compound 49 was the main identified compound among the seventy-three

different identified volatile compounds of C. sinensis, isolated from both leaves and stems at 20.79 % and 23.76 % of total contents, respectively [98]. The only isolated anthraquinone ester of these species, compound 12 is reported from an Indian study of C. australis stem barks and fruits using H-NMR, C-NMR, IR, and MS techniques [105]. Solely phenolic ester, compound 52, is detected from fruits, leaves, and young twigs of C. tournefortii via HPLC-TOF/MS methods [114], while the only steroid and fatty acid derivative ester, compound 50, is reported from crude methanolic extract of C. ehrenbergiana through GC-MS manner [109]. A Cameroonian investi- gation of acetone extract of C. adolphi-friderici roots isolated 3.3 mg of compound 27, the only reported ester of this species [103]. All the organic esters compounds obtained from the genus Celtis are sketched in Fig. 3.

1. Flavonoids

Flavonoids are the most documented components in Celtis species classified into flavanonol (compound 71), flavanol (compounds 58–64), flavonol (compounds 110–120), flavone (compounds 72–109), flavanone (compounds 65–70) , and anthocyanins (com- pounds 55–57) (Table 3). Leaves and fruits are the main reservoirs of these molecules, but they are also detected in the bark, young

twigs, and aerial parts (Table 3). Compound 59 is the most frequently reported flavanol in the Celtis species, isolated from various parts of C. pallida, C. tetrandra,and C. tournefortii [113,114,116,117], while the other flavanols are mainly epimers of compounds 58 and 59 (Table 3). However, compounds 108, 115, and 120 are the most commonly detected flavonoid molecules of the Celtis genus isolated from the various extracts of different parts of the five distinct species (Table 3). Compound 105, a flavone glycoside, was also isolated from four distinct Celtis species (C. africana, C. australis, C. occidentalis, and C. iguanaea) [121–123]. Among the conjugate molecules of

Fig. 2. Amides from the genus Celtis.

flavonoids, flavones and flavanone glycosides are the most extracted compounds (Table 3), while two new flavanol dimers (com-

pounds 63, and 64) are identified from the ethyl acetate extract of C. tetrandra barks using MS, H-NMR, C-NMR, and HRESIMS [116]. Ten flavonoids’ glycosides are attributed to compound 108 and its derivatives, discovered in the five following different species,

C. africana, C. australis, C. eriocarpa, C. occidentalis, and C. iguanaea [111,118,121–123]. In this study, all flavonoids of C. occidentalis

[118,122] and almost all of C. eriocarpa were identified as glycoside compounds, while most of the C. ericocarpa flavonoids were the

Fig. 3. Esters from the genus Celtis.

Fig. 3. (continued).

first time reported molecules [118]. Three different anthocyanins have been reported from the fruits and leaves of C. australis [32]. A

new C-triglycoside, compound 83, is obtained from the leaves of C. australis and C. occidentalis, whereas compound 81 is the primary isolated component of the n-butanol fraction of the same species’ leaves [122]. Compounds 94 and 95, two novel C-glycosylflavonoids, were discovered in ethanol and water extracts of C. africana aerial parts using HR-FAB-MS, H NMR, C-NMR, GC-MS, and EI-MS techniques [123]. All the organic acid compounds obtained from the genus Celtis are sketched in Fig. 4.

1. Organic acids

Among the various types of phytochemical molecules of Celtis species, organic acids and their derivatives are the second most reported compounds that can be divided into phenolic acids (compounds 167–172), hydroxycinnamic acids and glycoside (com- pounds 157–166), benzoic acids and derivatives (compounds 132–133, 135–138), fatty acids (compounds 139–156), as well as aliphatic carboxylic acids (compounds 124–131) (Table 3). Most of these compounds were identified in the aerial parts, roots, fruits, and leaves of Celtis plants. The most frequently documented organic acid in the Celtis species is compound 154, which is obtained from

various parts of six different species, including C. tournefortii, C. africana, C. australis, C. pallida,C. ehrenbergiana, and C. sinensis [27,32, 33,36,98,102,109]. Furthermore, compound 156 is reported from four different Celtis species namely: C. australis, C. pallida, C. sinensis, and C. tournefortii [32,33,36,98], while compound 153 is noted from three distinct species: C. africana,C. australis, and C. tournefortii [32,33,102].Compound 148 is extracted from hexane, ethyl acetate, and dichloromethane: methanol extract of C. africana leaves, fruits, and stems [27], while compound 145 is isolated from the only ethanol-water extract of aerial parts of the same species [102].

Along with compounds 139 and 143, 150–151, two different types of fatty acids are identified through UHPLC-DAD and ESI-MS

techniques from the crude methanolic extract of leaves of C. eriocarpa [118]. Seven fatty acids (compounds 140, 142, 146, 149, 148, 152, and 154) were reported from the ethanol-water extract of C. pallida aerial parts via the GC-MS method [36]. A saturated fatty acid compound 155, was solely isolated from the fruits of C. tournefortii [33].

In addition, six distinct phenolic acids (compounds 167–172), methanolic extracts of leaves of C. eriocarpa represent about 40 % of

the total reported hydroxycinnamic acids among the Celtiss pecies (compounds 158, 161, 163, and 164) [118]. Among the hydrox- ycinnamic acids, compound 159 is the most frequently isolated acid of the Celtis genus and was reported from three distinct species (C. australis, C. laevigata, C. pallida, andC. tournefortii) [78,113,114,126]. Two hydroxycinnamic acid compounds, 162 and 165, were

discovered using high performance liquid chromatography and time of flight mass spectrometry (HPLC-TOF/MS) techniques in methanol–dichloromethane extracts of C. tournefortii leaves and young twigs [114]. Compound 166 is solely reported from the fruits of

C. tournefortii [33]. Besides various kinds of organic acids, different types of aliphatic carboxylic acids (compounds 124–131) were

separated from five individual species (C. adolphi-friderici, C. eriocarpa, C. ehrenbergiana, C. tessmannii, and C. tournefortii) through various mass spectrometry techniques in different types of alcoholic or acetone extracts [36,97,103,109,118]. Compound 134 is the only carboxylic acid metabolite noted in this study, which was isolated from acetone extract of roots of C. adolphi-friderici [103]. All the organic acid compounds obtained from the genus Celtis are sketched in Fig. 5.

1. Terpenoids

The plants of the Celtis genus are also documented to possess a variety of terpenoid molecules (Table 3). Most of these molecules were discovered in aerial parts, barks, fruits, leaves, stem barks, and twigs. Among them, triterpenoids (compounds 184–201) are the most dominating terpenoids, with two of their esters (compounds 53–54). Apart from triterpenoids, compounds 178–179 are diter- penes, while the remainders are carotenoids (compounds 175–177) and tocopherols (compounds 180–183) (Table 3). Compound 181 is the often-reported terpene among the Celtis plants, detected in five individual species such as, C. africana,C. australis,

C. ehrenbergiana,C. pallida,and C. tournefortii [27,32,33,36,109]. However, among the triterpenoids, compound 193 is the most re- ported compound that has been found in four individual plants, including C. adolphi-friderici, C. africana,C. tessmannii, and C. iguanaea

[27,97,103,129]. Along with three triterpenoids (compounds 184–186), a triterpenoid glycoside, compound 201, was identified in the ethanol extract of C. australis [105]. Several derivatives (compounds 188–190) were recorded from Celtis species, while compound 191 was found in from methanolic extracts of stem barks of C. tessmannii [97], and the rest of compounds 188–190 were isolated from

C. philippinensis twigs and characterized via NMR and MS techniques [115]. Compound 194 is identified from the various extracts of

C. africana stems [27], while its epimer, compound 192, is reported from twigs of C. sinensis [101] as well as the barks of C. iguanaea [129]. Among the triterpenoids, compound 199 and 200 are found in three distinct species (Table 3), while diterpene compound 178 is also revealed in four different species (C. africana,C. iguanaea,C. pallida,and C. zenkeri) [27,36,99,108]. A novel bacteriohopanoid compound 174 has been isolated from the ethanol extract of C. australis bark [128]. Three different carotenoids (compounds

175–177), were isolated from the Croatian study on fruits of C. australis, where compounds 175 and 176 are two isomers [32]. The

compound 179, a derivative of compound 177 [133], has been identified in the fruits of C. tournefortii [33]. Along with compound 181, three different tocopherols were detected in Celtis plants, including C. africana, C. australis, and C. tourneforttii [27,32,33]. However, terpenoids were not reported from several Celtis species. Thus, further research is necessary to identify more terpenoid derivatives from other Celtis plants (Table 3). All the terpenoid compounds obtained from the genus Celtis are sketched in Fig. 6.

1. Miscellaneous compounds

Along with amides, organic acids, terpenoids, flavonoids, and esters, Celtis species have been found to possess a variety of addi- tional volatile chemicals such as acid anhydrates, lipids, aldehydes, esters, alkanes, benzopyrone, ketones, alcohols, sterols, tannins,

Fig. 4. Flavonoids from the genus Celtis.

Fig. 4. (continued).

sugars, and others (Table 3). These chemicals have been found in various plant parts, including leaves, fruits, stems, roots, twigs, and aerial parts. Many of these compounds are identified through phytochemical detection using different spectroscopic methods. Almost all aldehydes and ketone molecules from C. africana have been determined using 2D-GC-TOF/MS [27], while alcohol, sterol, sugar, and

amino acid of C. pallida were detected by GC-MS techniques [36]. The majority of the alcohol molecules have been identified from three species: C. pallida, C. africana, and C. sinensis [27,36,98]. In addition to two sterol glycosides, compounds 303–304, three in- dividual sterols, compounds 300–302, are noted from Celtis plants, while the compound 301 is the dominating among them, is found in seven different species (C. africana, C. australis, C. sinensis, C. tessmannii, C. adolphi-friderici, C. zenkeri, and C. pallida) [36,97,101–103, 127,134]. A cytotoxic novel glucosphingolipid, compound 288, is detected from the ethanol-water extracts of C. africana aerial parts

Fig. 5. Organic acids from the genus Celtis.

Fig. 5. (continued).

[37], whereas another glucosphingolipid, compound 289, is identified from acetone extracts of C. adolphi-friderici roots through H-NMR, C-NMR, HRESIMS, UV, IR techniques [103]. Moreover, some minor compounds, including tannin, sugar, stilbene, nitrogenous base, lignan, and benzopyrone, are also identified in Celtis plants (Table 3). Two phytotoxic benzopyrones, compounds 272 and 273, are documented in the aqueous extract of C. laevigata leaves [126]. The miscellaneous compounds found from the genus Celtis are sketched in Fig. 7.

Biological activities

Numerous bioactive constituents such as amides, organic acids, terpenoids, flavonoids, ester and several compounds present in Celtis species may account for their various health benefits, and therefore responsible for the vast pharmacological properties (Tables 4 and 5). However, only few species have been extensively studied for bioactivities.

1. Antimicrobial activities

Based on the Antimicrobial Resistance Collaborators study, the six bacteria pathogens causing resistance-related mortality, including Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseu- domonas aeruginosa, were responsible for 929,000 AMR-related deaths, while total AMR deaths in 2019 were 3.57 million [39]. This figure was higher than the mortality from AIDS and malaria [145]. However, the antibacterial capabilities of medicinal plants provide a possible option for addressing the growing challenges of AMR [40].

The species of Celtis genus may play some significant role because various parts of many Celtis species demonstrated a prominent antimicrobial activity, especially against S. aureus and P. aeruginosa (Table 4). Enormous reports have been noted on the antimicrobial activity of various parts of C. australis such as leaves [32,118,138], ripe fruits [31], and seeds [138]. Dichloromethane extracts of

C. laevigata demonstrated antimicrobial activity against two Mycobacteria organisms, including Mycobacterium tuberculosis and Mycobacterium avium, which were more active against Mycobacterium tuberculosis than Mycobacterium avium [35]. The ethanol extracts of aerial parts of C. pallida were tested against several types of bacteria (Escherichia coli, S. aureus, Bacillus subtilis, and P. aeruginosa), and fungus (Candida albicans); and showed low anti-microbial activity compared with the standard (Cefotaxime) [36].

In C. africana, various extracts of leaves, fruits, and stems exhibit tremendous antimicrobial activity against 2 gram-positive (Bacillus cereus and S. aureus) as well as 5 gram-negative bacteria (Klebsiella pneumoniae,Enterobacter aerogenes,P. aeruginosa,Proteus mirabilis, and E. coli). Among them, high potency was recorded from the hexane extract of fruits against S. aureus, while ethyl acetate extract of stems demonstrated a mild growth inhibitory effect against K. pneumonia, P. aeruginosa, S. aureus, P. mirabilis, and E. coli [27]. Hexane extracts of fruits and leaves demonstrated mild potency against only two organisms E. aerogenes and P. aeruginosa [27]. However, these extracts did not exhibit any activity against M. tuberculosis,B. subtilis,Klebsiella oxytoca,Enterobacter cloacae,Proteus vulgaris, and Staphylococcus epidermidis [27]. Intriguingly, an acetone extract of leaves of C. africana also showed potent antifungal activity against Cryptococcus neoformans (Minimum inhibitory concentrations (MIC) 0.22 mg/ml) [28].

Fig. 6. Terpenoids from the genus Celtis.

Fig. 6. (continued).

Three different extracts of C. tournefortii fruits displayed the growth inhibition of B. subtilis,Bacillus megaterium,S. aureus,E. coli,

P. aeruginosa,Listeria monocytogenes,K. pneumonia,P. vulgaris, and C. albicans [33]. Its water extract exhibited a narrow spectrum of activity and only showed inhibition against gram-positive bacteria (B. subtilis, B. megaterium, and S. aureus), while both ethanol and

(caption on next page)

Fig. 7. Miscellaneous compounds from the genus Celtis.

methanol extracts demonstrated broad-spectrum antibacterial activity, and methanol extract further showed antifungal activity against C. albicans [33]. In comparison to the growth inhibition activity of standard (10 mg/disc streptomycin sulfate and 30 mg/disc nystatin), methanol extract demonstrated superior antibacterial action against L. monocytogenes and B. subtilis [33]. Further studies are needed to identify the antimicrobial components of the methanol extract.

Among the plants of the Celtis genus, various extracts of different parts (leaves, seeds, and ripe fruits) of C. australis have notable antimicrobial activity against bacteria and fungus, even on resistance strains (Table 4). Leaf methanolic extract showed good anti- microbial potency against S. aureus and P. aeruginosa despite their resistance to Cefuroxime, Ampicillin, and Tetracycline. So, it is predictable that methanolic extract may have antibacterial components that show potency against resistant strains [30]. Another study

on ripe fruits of C. australis revealed that ethanol extract had potent antimicrobial effect against B. subtilis and P. aeruginosa (250 μg/ml and 125 μg/ml MICs, respectively) [31]. Furthermore, the ethanolic leaf (harvested at the end of October) extract has antifungal action against C. albicans, Candida parapsilosis (MIC 0.156 mg/mL), and R. mucilaginosa (MIC 0.313 mg/mL) [32], whereas the

= =

hydromethanol and ethyl acetate extracts of leaves and seeds have antifungal activity against C. albicans, Candida tropicalis, and

Aspergillus niger [138]. Among them, hydromethanol extract outperforms ethyl acetate extract in antifungal activity. In the case of

A. niger, hydromethanol extract of both seeds and leaves showed greater activity than the standard fluconazole. However, compared to nystatin, only leaves hydromethanol extract is as effective as nystatin [138]. Further hydromethanol extract of leaves study is needed to find out what the antifungal compound in them is. Along with anti-fungal action, ethyl acetate extract has remarkable anti-bacterial activity. The ethyl acetate extracts of the leaves and seeds are active against both gram-positive (Bacillus. spp,Bacillus cereus,Listeria ivanovii,and S. aureus) and gram-negative (C. freundii,E. coli, and S. sp) bacteria [138]. In particular, leaves ethyl acetate extract strongly reduced the growth of Citrobacter freundii and E. coli, while seeds ethyl acetate extract was more potent against Bacillus. spp,

L. ivanovii, and Staphylococcus spp. [138].

In the Celtis genus, various types of fatty acids are isolated from the species that may be involved in broad-spectrum antimicrobial activities. Recent biological research on fatty acids has found possible antibacterial mechanisms, such as inhibiting protein synthesis, DNA/RNA replication, cell wall, metabolic route, and quorum sensing (QS), as well as horizontal gene transfer (HGT), cytoplasmic membrane disruption, and efflux pumps, that may help reduce bacterial growth, even in resistant strains [146]. Compounds 154 and 156 are two familiar saturated plant-fatty acids also detected in these Celtis plants, both of which exert antibacterial action against gram-positive and gram-negative bacteria. Their nanostructure arrays successfully suppress the growth of P. aeruginosa and S. aureus [147], which are inhibited by the majority of various plant extracts of the Celtis genus (Tables 4 and 5).

They showed bactericidal action against vancomycin-resistant Enterococcus faecalis (VREF) and multidrug-resistant Staphylococcus epidermidis (MRSE) while encapsulated in liposome carriers [41]. Additionally, Parsons et al., stated that unsaturated fatty acid including compound 155 is noxious to metabolism because it is not good enough for phospholipid biosynthesis and accumulates in the cells of bacteria [148]. In this way, it affects the cell membrane and its functions, such as the proton gradient, and inhibits macro- molecular synthesis, which ultimately leads to energy loss [148]. Another phyto-fatty acid, compound 147, also alters the bacterial metabolic pathways of S. aureus [149] through its ability to alter gene expression in glycolytic and fermentative systems that are essential for energy production [146]. Furthermore, compounds 155 and 147 selectively inhibit bacterial enoyl-acyl carrier protein reductase (FabI), a key molecule in bacterial fatty acid generation [150]. The liposomal form of unsaturated fatty acid (compound 148)

exhibits minimum bacteriacidal concentration (MBC) against Helicobacter pylori at 200 μg/mL through increasing the permeability of

the outer membrane [151].

The presence of phenolic compounds in the Celtis genus may also be responsible for the enhancement of antibiotic activity even against resistant pathogens. Compound 297 displays antimicrobial activity on several microorganisms such as A. niger,Aspergillus fumigatus,Aspergillus flavus,Aspergillus ochraceus,Alternaria alternata,Botrytis cinerea,Candida. spp,Penicillium citrinum,Penicillium chrys- ogenum,Fusarium oxysporum, and Rhizopus oryzae through cell membrane disturbance [152]. The compound has bactericidal activity against H. pylori at low pH levels. However, the organism remained susceptible to the compound even after undergoing ten successive generations of growth at concentrations below their inhibitory levels, without developing any resistance [153]. Furthermore, this phytoconstituent also inhibits biofilm formation as well as breaks cell-to-cell communication in Methicillin-resistant Staphylococcus aureus (MRSA) at 0.04 % v/V concentration [42]. Compounds 71 and 65 inhibit vancomycin-resistant E. faecalis by binding to Beta-Ketoacyl-[acyl carrier protein]-synthase (KAS) III, which is required for bacterial fatty acid synthesis [154]. Other compounds, such as Genistein (aglycone of compound 123), compounds 112, 115, 114, 76, 122, and 305, exhibit activity against various mi-

croorganisms, even on resistant strains, at various concentrations [155–159]. Another mechanism of action, “inhibition of d-Alanine:

d-alanine ligase,” is shown by compounds 115 and 73 against H. pylori and E. coli [160]. Though compound 113 cannot affect bacterial growth, it can restrain the virulence of pathogenic bacterial strains, like S. aureus via Sortase A and B inhibitors [161].

Some terpenoids and their derivatives that have antimicrobial activity are also detected in Celtis genus plants (Table 3). Terpenes are more susceptible to gram-positive than gram-negative bacteria. Their lipophilic feature is mainly responsible for their antimi- crobial response [162]. Compound 190, a pentacyclic triterpenoid, has anti-staphylococcal activity against S. aureus. However, their individual actions are weaker than the common antibiotics. They produce a synergistic effect with the combination of beta-lactam and glycopeptide class antibiotics through cell wall inhibition. Among them, compound 191 and methicillin are the most effective com- binations [163]. Another familiar phyto-triterpenoid of Celtis species, compound 200, has broad-spectrum antibacterial activity. In the Langmuir monolayer technique, this phytoconstituent displayed a disorganizing effect on the applied model of the E. coli membrane [164].

Table 4

Biological activities of extracts of Celtis genus.

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

Ref no.

Anti-diabetic activity C. philippensis Crude, Ethyl

acetate, Ethanol, and Aqueous extracts

Leaves In

vivo

Various solvent extract- treated groups of Wistar albino rats saw a considerable reduction in their peak blood glucose levels around day 14 of the experiment. However, the extract improved HDL levels relative to the glycemic group, indicating antilipidemic potential.

Glibenclamide [135]

Anti-diarrheal activity C. africana Aerial parts Organic fraction In

vivo

C. pallida Aerial parts Ethanol extract In

vivo

At a high dose, fractioned showed spasmolytic activity in rabbits through

the Ca++ antagonist

induced gut relaxation. Inhibited diarrheic defecation in BALB/c mice in a dose-dependent manner

Loperamide [136]

Loperamide [36]

Anti-inflammatory/ Analgesic activity

C. australis Barks, fruits, fatty acids (fruits)

Ethanol extracts of barks and fruits, fatty acids from ethyl acetate extracts

In vivo

On Swiss albino mice, 500 mg/kg extracts of barks and fruits and fatty acids showed a moderate analgesic effect against acetic acid-induced writhes.

On adult female Sprague- Dawley rats, crude extracts and fatty acids suppressed carrageenan- induced paw edema was significant at all concentrations (100 mg/

kg, 250 mg/kg, and 500 mg/kg) compared to the standard phenylbutazone.

Paracetamol and Phenylbutazone

[137]

C. choseniana Leaves Methanol extract In vivo, In vitro

C. pallida Aerial parts Ethanol extract In

vivo Anti-microbial activity C. africana Fruit Hexane extract In

vitro

C. africana Leaves Acetone extract In vitro

C. africana Leaves Hexane extract In vitro

In both in vivo and in vitro studies, it suppressed nitric oxide generation as well as mRNA expression of inducible nitric oxide synthase, tumor necrosis factor-alpha, and cyclooxygenase-2.

Decreased 30 % in ear inflammation of mice Against four types bacteria including E. coli,

P. mirabilis, S. aureus, and

B. cereus (MIC 32 mg/ml). Lowest MIC 4 mg/ml was recorded against

S. aureus.

Showed inhibition activity against

C. neoformans (MIC =

0.22 mg/ml)

Against P. aeruginosa, and

E. aerogenes (MIC 32 mg/ ml)

C. africana	Stem	Ethyl acetate extract	In	Against K. pneumonia,	Streptomycin	[27]
			vitro	P. aeruginosa, S. aureus,

Prednisolone [68]

Indomethacin [36]

Streptomycin [27]

Amphotericin B [28]

Streptomycin [27]

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

P. mirabilis, and E. coli

(MIC 32 mg/ml).

Ref no.

C. africana Stem bark Ethanol extract In

vitro

C. australis Leaves Ethanol extracts In vitro

Showed moderate anti- plasmodic activity against

P. falciparum 3D7 strain (IC₅₀ = 29.05 μg/ml) More efficient against

C. albicans, C. parapsilosis (MICs = 0.156 mg/ml) than R. mucilaginosa(MIC

= 0.313 mg/ml).

C. australis	Leaves and seeds	Hexane, and ethyl	In	Demonstrated better	Tetracyclin and	[138]
		acetate extract	vitro	activity against Bacillus.	Penicillin G
				sp, B. cereus, L. ivanovii,
				C. freundii, and E. coli than
				S. aureus.
				C. freudii and E. coli were
				significantly inhibited by
				leaf ethyl acetate,
				whereas B. sp, L. ivanovii,
				and Salmonella sp were
C. australis	Leaves and seeds	Hydro-methanol and	In	more sensitive to seed Extract of leaves showed	Nistatine and	[138]
		ethyl acetate extract	vitro	inhibition against A. niger	Fluconazole
				and C. albicans
				(hydromethanol) and
				C. tropicalis (ethyl
				acetate). Both leaves and
				seeds ethyl acetate and
				hydromethanol (leaves
				and seeds) showed
				inhibitory effects on
				Candida albicans, while
				fluconazole and nistatine
				had no effect on them.
				Hydromethanol > Ethyl
				acetate.
				Nystatin >
C. australis	Leaves	Water and methanol	In	Hydromethanol > Against P. aeruginosa and	Cephotaxime	[30]
		extracts	vitro	S. aureus. Between the two
				extracts, methanol
				showed the highest
				antibacterial activity.
				Activity was also recorded
				against the resistance
				strains of cefuroxime,
				ampicillin, and
				tetracycline.
				Methanol > Water.
C. australis	Ripe fruits	Ethanol extract	In	Can be used in the case of Activity against	Ampicillin	[31]
			vitro	P. aeruginosa and
				B. subtilis. MICs were 250
				μg/ml and 125 μg/ml,
C. laevigata	Plant materials	Dichloromethane	In	respectively Showed better efficiency	Rifampin	[35]
		extract	vitro	against Mycobacterium
				tuberculosis (99 %) than
C. pallida	Aerial parts	Ethanol extract	In	Mycobacterium avium (39 Mild antimicrobial	Cefotaxime	[36]
			vitro	activity against B. subtillis,

Artemisinin [29]

N/A [32]

ethyl acetate.

Fluconazole (A. Niger)

resistance

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

E. coli, P. aeruginosa, S. aureus, and C. albicans

Ref no.

C. tournefortii Fruits Ethanol extract In vitro

C. tournefortii Fruits Methanol extract In vitro

C. tournefortii Fruits Water extract In vitro

(MICs = 400 μg/ml).

Extract showed activity against L. monocytogenes,

E. coli, S. aureus,

P. aeruginosa,

K. pneumonia,

B. megaterium,

P. aeruginosa, B. subtilis bacteria, and C. albicans fungus.

Activity was recorded against P. vulgaris, B. megaterium, E. coli,

L. monocytogenes, P. aeruginosa, K. pneumonia,

B. subtilis, S. aureus bacteria and C. albicans fungus.

Better than standard (streptomycin and nystatin) against

L. Monocytogenes, and

B. Subtilis.

Activity was noted against

S. aureus, B. subtilis, and

B. megaterium.

Streptomycin sulfate (10 mg/ disc) and Nystatin (30 mg/disc)

[33]

C. tournefortii Leaves Aqueous extract (Silver Nanoparticles)

In vitro

Silver nanoparticles at doses of 0.06–0.13 μg/mL and 0.50–1.00 μg/mL

showed effective inhibitory action against gram-positive bacteria

S. aureus and B. subtilis, while gram-negative bacteria E. coli, and

P. aeruginosa. Silver nanoparticles were also effective against

C. albicans growth at 0.03 g/mL, a significantly lower dosage than antibiotics.

[34]

Antiulcerogenic activity

C. iguanaea Ethanolextract Leaves In vivo

C. iguanaea Hexane extract Leaves In vivo

The activity was shown to protect from indomethacin, ethanol, and pyloric ligation- induced gastric ulcers in male Swiss mice. The hexane fraction of this extract reduced indomethacin-induced ulcers by suppressing the release of gastric acid, increasing pH, and decreasing acidity without interrupting intestinal motility through the anticholinergic mechanism.

The activity of this species reduced indomethacin and pyloric ligation-

Ranitidine [139]

Ranitidine [140]

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

induced gastric ulceration and lesion index in the experimental models. It blocked the histamine and cholinergic receptors that hindered the cell molecular events of gastric secretion as well as

suppressed the total H+

excretion.

Ref no.

Cytotoxic /Anticancer activity/ Antiproliferative activity/Anti- tumor activity

C. aetnensis Twigs Chloroform extract In vitro

Extract reduced human colon cancer cell line (Caco2) cells by apoptosis at the low dose (5 μM) and necrosis at high dose (250 μg/ml). This extract increased ROS levels,

decreased RSH levels, and increased heme oxygenase (HO-1) expression.

Untreated control group

[38]

C. africana Aerial parts Ethyl acetate extract In

vitro

Showed the highest

cytotoxicity (EC₅₀ = 8.3

μg/ml) among the other

extracts such as petroleum-ether, chloroform, and n- butanol against mouse lymphoma cells L5178Y, while positive control Kahalalide F exhibited an

EC₅₀ of 6.3 μg/ml.

Kahalalide F [37]

C. eriocarpa Leaves Methanolic extract, n- Hexane fraction, Chloroform fraction, Ethyl acetate fraction, and Aqueous fraction

In vitro

The highest cytotoxin LC₅₀ was noted from ethyl acetate fraction against Brine shrimp larva at

243.61 μg/ml, while

positive control potassium dichromate

revealed LC₅₀ at 7.04 μg/

ml. Among them, the LC₅₀ value ranged from 243.61

μg/ml to 1015 μg/ml. The

n-hexane fraction produced the lowest activity.

Ethyl acetate fractions >

methanol extracts > chloroform fractions > Aqueous fractions > n- Hexane.

Potassium Dichromate

[118]

C. eriocarpa Leaves Methanolic extract, n- Hexane fraction, Chloroform fraction, Ethyl-acetate fraction, and Aqueous fraction

(In vivo/ In vitro)

Compared with camptothecin (positive control), activity was shown against Agrobacterium tumefaciens induced tumors on potato discs, but the result was insignificant.

Camptothecin showed an IC₅₀ value of 3.67 μg/ml, while leaf extracts’ IC₅₀ values ranged from 372 μg/ml to 1057 μg/ml.

Ethyl acetate fraction >

Methanol extract >

Camptothecin [118]

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

Chloroform fraction > Aqueous fraction > Hexane fraction

Ref no.

C.iguanaea Leaves Dichloromethane, and Hexane extract

In vitro

Dichloromethane showed activity against human ovarian (OVCAR-3), lung (NCI–H460), and

glioblastoma (U-251) tumour cells, with GI₅₀

values of 28.46 μg/ml,

32.31 μg/ml, and 37.99

μg/ml, respectively.

On the other hand, hexane extract showed activity against human glioblastoma (U-251), ovarian (OVCAR-3), and colon (HT-29) tumour cells, with GI₅₀ values of

6.40 mg/ml, 3.99 mg/ml, and 3.16 mg/ml, respectively.

Hexane extract >

Dichloromethane extract

Doxorubicin

[108]

C. tournefortii Fruits Ethanol extracts In vitro

C. tournefortii Fruits Methanol extracts In vitro

C. tournefortii Fruits Water extracts In vitro

Ethanol extract demonstrated better activity than water and methanol extracts against PC-3.

Methanol extract exhibited better activity than water and ethanol extracts against A2780. Water extract showed better activity than ethanol and methanol extracts against MCF-7, HCT-116.

Cell were treated with DMSO (Solvent-control group)

[33]

C. tourneforti Leaves Aqueous extract (Silver-nanoparticle)

In vitro

Silver nanoparticles of leaves extract showed effective on CaCo-2 cell line. Morever, low activity was detected against healthy cell line HDF.

[34]

Healing wounded C. australis Seeds Ethyl acetate extract In

vivo

Hepatoprotective	C. tournefortii	Fruits	Aqueous, 25 %	In	Activity was shown to	N/A	[142]
			ethanol, and 75 %	vivo	protect against Cu-
			ethanol		induced hepatic cell
					damage in Wistar Albino
					rats. Fruit extracts
					significantly emaciated
					the degenerative and
					necrotic destruction of the
					Cu-induced hepatic
					damage in the rats. It may
					increase the antioxidant
					activity that assuages the
					destruction of the Cu-
C. tournefortii		Leaves	Aqueous, ethanol-	In	Activity was shown to	N/A	[143]
			aqueous (1:3 v/v), and	vivo	protect against CCl₄–
			ethanol-aqueous (3:1		induced hepatic cells
			v/v)		damage in Wistar albino

In Sprague-Dawley rats, the wound healing rate was as same as the standard ointment rates.

Mad´ecassol® [141]

induced toxicity.

Activity Species Part

Extract

In vitro/ In vivo

Key findings Positive control/ Standard

rats. Results revealed that the leaf extract tremendously lessened the CCl₄-induced degenerative and necrotic

destruction of the rat’s

hepatic tissue by enhancing the antioxidant activity. It has the potential to be used as a hepatoprotective agent.

Ref no.

Laxative (prokinetic) C. africana Aerial parts Aqueous fraction In

vivo

Rabbits demonstrated dose-dependent spasmogenic action at low

dosages of 0.03–3 mg/ml,

which contracted the

rabbit’s jejunum. It displayed atropine-

sensitive prokinetic and laxative actions.

Carbachol [136]

Rumen fermentation C. pallida Leaves Hydroalcoholic extract N/A Significantly

improvement of rumen fermentation at doses 1.2–1.8 ml/g dry matter

of diets

N/A [144]

After the aforementioned, it can be concluded that the various mechanisms of antimicrobial activity of Celtis species depend on the plant compounds as well as the types of extract solvent (polar and non-polar). Furthermore, Celtis may show some hope for antimi- crobial resistance disaster, because of some isolated compound of Celtis showed positive effect on the VREF, MRSE, and MRSA. However, the majority of the published articles are based on in vitro tests, which may not assure the same results in animal models or clinical conditions. With the increase of antibiotic-resistant pathogenic bacteria, there is an urgent need to find novel antimicrobial drugs, while phytoconstituents from plants such as Celtis could be promising alternatives.

1. Anticancer, antitumor, and antiproliferative activities

Cancer is among the ailments that kill large numbers of people every year throughout the world. A study shows that in southern Thailand raw seed consumption has remarkable healing properties in the occurrence of esophageal cancer [165]. Among three different extracts of C. tournefortii fruits, the water extract showed better activity against human breast cancer (MCF-7) and human colon cancer (HCT-116) than the ethanol and methanol extracts. However, ethanol extract showed superiority against human prostrate cancer (PC-3), while methanol extract was more efficient against human ovarian cancer (A2780) cell lines [33]. A new glucos- phingolipid (compound 235), isolated from C. africana, displayed potent cytotoxicity against mouse lymphoma cells L5178Y, nearly the same as the positive control Kahalalide F and better than other extracts such as ethyl acetate, petroleum-ether, chloroform, and n-butanol extract [37] (Table 5). Methanolic extract and its various fractions of C. eriocarpa leaves exhibited cytotoxicity against Brine shrimp larvae, while the ethyl acetate fraction showed more efficiency than the other fractions (n-Hexane, chloroform, and aqueous) and the methanolic extract [118]. Another chloroform extract of C. aetnensis twigs induced apoptosis in a Human Colon Cancer (Caco2) cell lines at a low dose, and necrosis at a high dose through the increase of reactive oxygen species (ROS) levels, heme oxygenase (HO-1) expression, and decreasing reactive thiol group (RSH) levels [38].

Some familiar plant bioactive compounds are also identified from investigated Celtis species to have tremendous anticancer ac- tivity. Compound 147 is such a bioactive compound and one of the frequently occurring fatty acids in Celtis species (Table 3), that in high doses decreases the proliferation of Caco-2 cell line [166], with a protective effect against cancer growth [167]. Another fatty acid of Celtis species, compound 154, demonstrated selective cytotoxicity by promoting apoptosis in the human leukemic (MOLT-4) cell line. Compound 154 exerts an anticancer effect in mice by targeting tumor cell DNA topoisomerase I. Surprisingly, it does not affect DNA topoisomerase II, indicating that compound 154 can be used as an anti-cancer medicine [168]. Furthermore, conjugation of N-acylhydrazones, with compounds 149, 153, and 147 displays activity against human breast cancer (MCF-7), leukemia (HL-60),

cervix (KB–V1/Vbl), and melanoma (518A2) carcinomas, while conjugation with compounds 149 is three times better than Doxo- rubicin [169]. A familiar plant’s flavone glycoside, compound 105, isolated from four distinct Celtis species (C. africana,C. australis,

C. occidentalis, and C. iguanaea) suppresses cell growth, invasion, and migration. In Adeno-carcinomic human alveolar basal epithelial (A549) cell lines, it reduces Cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expression by upregulating MicroRNA 26b (miR-26b) and MicroRNA 146a (mir-146a) [170]. Furthermore, the compound 105 and celecoxib combination demonstrate a synergistic impact

Table 5

Biological activites of the phytoconstituents of Celtis genus.

Activity name Comp. Number Plants In

vitro/ In vivo

Key findings Positive control/

Standard

Ref. no

Anticholinergic activity

Compound 8 C. sinensis In vivo

Exhibited a dose-dependent acetylcholinesterase inhibitory effect in a dose- dependent response at male ICR mice

Berberine [104]

Compound 8,

compound 10,

compound 6

C. africana In vitro Three of them showed moderate

acetylcholinesterase inhibitors effects. Compound 10 > compound 6 > compound 8

Galanthamine [102]

Anti-inflammatory/ analgesic activity

Compound 125 C. adolphi- friderici

In vitro Compound 125 (IC₅₀ = 16.3 μM) showed high

potent anti-inflammatory activity, even better than standard Baicalein.

Baicalein [103]

Compound 131 C. tessmannii In vitro Activity against lipoxygenase was more than Baicalein [97]

Compound 101 C. sinensis In vivo

the standard (Baicalein). (IC₅₀ = 12.9 μM) In vivo, compound 101 decreased inflammatory molecules (IFN-α, TNF-α, IL-2,

and IL-17A) in the lymphatic system, inhibited cytokine release into the serum, and increased apoptosis-related protein production in ginkgo acid-induced contact dermatitis in ICR mice. Additionally, in vitro, Con A-activated T cells showed death and decreased inflammatory cytokines. This chemical blocked MAPK and STAT signaling and phosphorylated SHP2.

Dexamethasone [124]

Compound 8,

compound 10,

compound 6

C. africana In vivo In rats’ carrageenan induced paw edema,

compound 8 exhibited remarkable action,

whereas compounds 3 and 4 exhibited only mild action. compound 8 > compound 10 > compound 6

Diclofenac sodium

[102]

Anti-microbial activity

Compound 138 C. australis In vitro Activity was shown against gram positive

bacteria including B. sp, B. cereus, L. ivanovii, and S. aureus. (MICs = 25–100 μg/ml). Most active against B. cereus (MICs = 25 μg/ml)

Demonstrated activity against gram negative bacteria such as C. freundii, E. coli, and S. sp.

Tretracycline [127]

Compound 191 C. tessmannii In vitro

(MICs = 25–100 μg/ml)

Showed potency anti-plasmodium activity against various chloroquine-sensitive and

resistant P. falciparum strains. (IC₅₀ = 2.38–1.7

μg/ml)

N/A [97]

Compound 301 C. australis In vitro Against gram positive bacteria such as B. sp,

B. cereus, L. ivanovii, and S. aureus. (MICs =

100–200 μg/ml)

Against gram negative bacteria including

Tretracycline [127]

Compound 303 C. australis In vitro

E. coli and S. sp. (MICs = 200 μg/ml)

Showed activity against gram positive bacteria

such as B. sp, B. cereus, L. ivanovii, and S. aureus. (MICs = 50–200 μg/ml)

Activity was demonstrated against gram negative bacteria such as C. freundii, E. coli, and

Tretracycline [127]

Cytotoxicity/Anti- cancer activity/ Anti- proliferative activity/Anti- tumor activity

Compound 200 C. philippinensis In vitro

S. sp. (MICs = 100–200 μg/ml)

Activity showed better against oral epidermoid than other such as against human lung, colon, oral epidermoid, and hormone-dependent prostate cancer.

oral epidermoid > hormone-dependent

prostate > colon > lung

Paclitaxel and Camptothecin

[115]

Compound 53 C. philippinensis In vitro Activity showed better against oral epidermoid

than other such as against human lung, colon, oral epidermoid, and hormone-dependent prostate cancer.

oral epidermoid > hormone-dependent

prostate > colon > lung

Compound 54 C. philippinensis In vitro Activity showed better against oral epidermoid

than others such as human lung, colon, oral epidermoid, and hormone-dependent prostate cancer.

oral epidermoid > hormone-dependent

prostate > lung > colon

Paclitaxel and Camptothecin

[115]

(continued on next page)

Table 5 (continued )

Activity name Comp. Number	Plants	In vitro/	Key findings	Positive control/	Ref. no
Compound 288	C. africana	In vitro	Demonstrated better cytotoxicity (EC₅₀ = 7.8	Kahalalide F	[37]

In vivo

Standard

μg/ml) than other extracts, such as ethyl

acetate, petroleum-ether, chloroform, and n- butanol extract, against mouse lymphoma cells L5178Y, as well as near to the standard Kahalalide F.

Compound 302 C. iguanaea In vitro Activity was shown against human liver,

breast, colon, and lung tumor cell lines through cell cycle arrest and apoptosis.

Doxorubicin

[108]

Compound 58,

compound 60,

compound 59

Compound 63,

compound 64

C. tetrandra In vitro Compounds demonstrated remarkable activity

in overcoming TRAIL (Tumor necrosis factor (TNF)-related apoptosis-inducing ligand) resistance in AGS (human gastric adenocarcinoma) cells. It can be used to treat the TRAIL resistance AGS cell.

C. tetrandra In vitro These two flavanol dimers showed low potency

to overcome TRAIL resistance in AGS cells.

Luteolin [116]

Urease inhibitory Compound 131 C. tessmannii In vitro Compound 53 was reported as having the most

potent anti-urease activity even more than the standard thiourea.

Thiourea [97]

Compound 193 C. adolphi- friderici

Compound 77 showed the very high potent anti-urease activity even more than thiourea (standard).

Thiourea [103]

Compound 301 C. zenkeri In vitro It was more potent inhibitor against the Jack

bean urease (IC₅₀ = 20.3 μM), than the

Thiourea [90]

Compound 304 C. zenkeri In vitro

standard (thiourea- IC₅₀ = 21.5 μM)

In comparison to the standard (thiourea- IC₅₀

= 21.5 μM), it was high moderate inhibitor of

Thiourea [90]

Compound 108,

compound 100,

compound 99,

compound 105,

C. africana In vitro

the Jack bean urease (IC₅₀ = 27.6 μM). Compound 108, compound 105, compound 99 and compound 100 showed potent urease inhibitory activity.

Compound 105 > compound 108 > compound 99 > compounds 100

Thiourea [123]

*Compound number indicates the compound’s serial number of Table 3.

on cell invasion and migration in A549 cell lines through the inhibition of COX-2, inducible nitric oxide synthase (iNOS), and B-Cell Leukemia 2 expression with the activation of the apoptosis-inducing gene “Cytochrome P450 Family 1 Subfamily A Member 1” [170]. The results show that both compound 105 and its combination could be a potentially effective medicine that kills cells by causing inflammation.

Cytotoxic terpenoids are also detected from Celtis genus. For example, compound 199, which is separated from fruits of C.africana [27], can reduce a significant portion of rats’ aberrant crypt foci (ACF) in the colon. The possible mechanism is that it may be able to stop “3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase” or bile acids that lead to colonic tumors or ACF [171]. Compounds 58 and 60, two flavanol epimers of the bark of C. tretranda, contribute to human gastric adenocarcinoma (AGS) cells regain from Tumor

Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) resistance-overcoming properties much more than their dimers, com- pounds 63 and 64 [116].

Because of their ability to block the expression of numerous tumor-and angiogenesis-associated genes, phytoconstituents may also enhance apoptotic signaling channels by reducing activating caspases, as demonstrated by analogous molecules from other plant genera [172], along with significant downregulation of DNA synthesis. Additional investigation is needed to put emphasis on the probable pharmacological mechanisms that are involved in anticancer activity. Also, the results of the experiments need to be backed up by a lot of research on human carcinoma cell lines.

1. Anti-inflammatory activity

Almost every clinical manifestation is accompanied by a proinflammatory response. As a result, the anti-inflammatory properties of Celtis plant materials may be useful. Various kinds of inflammation have been used to test the anti-inflammatory activities of C. australis barks and fruits [137], C. pallida aerial parts [36], as well as C. choseniana leaf extracts [68].

The anti-inflammatory properties of ethanolic extracts of barks and fruits of C. australis were reported via their remarkable

reduction of carrageenan-induced paw edema. The same study also revealed the analgesic effects of C. australis by inhibition of acetic acid-induced writhes in Swiss albino mice [137]. However, the extracts’ outcomes against inflammation were better than the fatty acid experiment [137]. Leaves of C. choseniana decrease nitric oxide generation as well as mRNA expression of iNOS, COX-2, and tumor necrosis factor-alpha (TNF-α) [68]. Further investigation revealed that this extract contained anti-inflammatory flavonoids such as

compounds 112, 115, and 76 [68].

Compound 25, an isolated phytoconstituent from C. africana fruits, leads to anti-inflammatory effect by suppressing iNOS and COX- 2 [173], whereas compound 131 of C. tessmannii acid shows activity by inhibiting lipoxygenase [97] (Table 5). Compound 148 also

reduces lipoxygenase induced interleukin-1 (IL), IL-6, and TNF-α [97]. Additionally, TNF-α production is also inhibited by C. sinensis

lignan glycoside [101].

From the aforementioned, it is apparent that Celtis genus bioactive molecules decrease inflammatory components through the interrupting cyclooxygenase, and lipoxygenase pathway, which may lead to reduce the generation of inflammatory mediators such as IL and TNF-α.

1. Anti-diarrheal and prokinetic activity

The antidiarrheal effect of the Celtis genus has been investigated through many animals’ model, such as rabbits and BALB/c mice. The chloroform fraction of ethanol: water (8:2) extract of C. africana aerial parts reduced the frequency of stooling in rabbits at a high dose [136]. An ethanol extract of C. pallida aerial parts exhibited dose-dependent antidiarrheal activity via diarrheic defecation in

BALB/c mice [36]. Conversely, the aqueous fraction of ethanol: water (8:2) extract of C. africana aerial parts demonstrated

atropine-sensitive prokinetic activity at lower dose by contracting rabbits’ jejunum [136]. Medicinal plants are generally known to have antidiarrheal properties through stimulating the intestinal K+ channels and activating Na+/K+- ATPase activity, as well as reducing intracellular Ca++ concentration, facilitating gastrointestinal smooth muscle relaxation as well as reducing diarrhea

[174–176]. Further studies are necessary to isolate the potential anti-diarrheal compounds from Celtis species extracts, which may lead to get a new gut relaxation agent.

1. Acetylcholinesterase inhibitory activity

Acetylcholinesterase is responsible for the cessation of signal transduction of several cholinergic systems in the central and pe- ripheral nervous systems by efficiently breaking down the neurotransmitter acetylcholine [177]. From the Celtis genus, different hydroxycinnamic acid derivative amide compounds, 8, 10, and 6, were detected in the ethanol-water extract of C. africana aerial parts, which showed a weak to moderate acetylcholinesterase inhibition activity [102]. Compound 8 is also isolated from twigs of C. sinensis [104]. As per their structure, compound 8 has a hydroxy group at the 4th position, while compound 10 has an extra methoxy group at the 3rd position that may be accountable for its better activity. However, the most active constituent among them, compound 6, has two additional hydroxy groups at the 3rd and 4th positions, which may be responsible for the strongest activity [102]. As per our knowledge, despite their structure-activity-relationship, the exact mechanism of action against acetylcholinesterase is still obscure. Additional investigation is needed to learn about their mechanism of action, which may lead to the invention of a novel acetylcho- linesterase inhibitory molecule.

1. Anti-urease inhibitory activity

The nickel-containing enzyme, urease, plays a vital role in the breakdown of urea to generate ammonia and CO₂ [178]. The urease activity of H. pylori plays a crucial role in the etiology of gastric and peptic ulcers [179]. So, plant-urease inhibitors are potent compounds that can be used as anti-ulcer medications. The urease inhibitory effect of Celtis plants was revealed in several isolated compounds of three species including C. adolphi-friderici, C. tessmanii, and C. africana (Table 4). A triterpene, compound 193, detected

from the roots of C. adolphi-friderici exhibited more potent anti-urease activity (50 % inhibitory concentration (IC₅₀) = 15.36 μM) than other isolated compounds from this species, even more, effective than standard thiourea (IC₅₀ = 21.6 μM) [103]. Compound 131, another phytoconstituent, that was isolated from C. tessmanii, also had more efficacy anti-urease activity (IC₅₀ 12.9 μM) than thiourea [97] (Table 5). Four constituents, including compound 108, compound 105, 99, and 100 of C. africana demonstrated potent

anti-urease activity, while the other three compounds 94, 95, and 109 were not as efficacious as the previous four constituents [123]. As per their structure, the presence of a sugar moiety might reduce their potential anti-urease activity [37].

Isolated compounds of Celtis species have tremendous potential as urease inhibitory constituents. Despite their remarkable activity against the urease enzyme, their precise mechanism of action remains unknown. Moreover, all investigation has been done under an in vitro test. A clinical trial is necessary to evaluate their in vivo potency, which may lead to the establishment of a new potent anti-urease medication.

1. Other medicinal properties

Aside from the previously mentioned activities, the isolated phytoconstituents and extracts have several protective functions. For example, compounds 148 and 199 have neuro- and hepatoprotective effects, respectively [180,181]. Ethyl acetate extract of

C. australis seeds had remarkable wound healing efficacy comparable to that of standard ointment [141]. Furthermore, detected flavonoids such as compounds 106, 67, and 69 have cardioprotective properties due to their immunosuppressive and antioxidant properties [182–184]. More research is needed to investigate the various processes involved in the aforementioned positive benefits.

Antioxidant properties

Besides performing several biological functions, extracts and compounds of Celtis plants exhibit remarkable antioxidant activity (Tables 6 and 7). Their abilities to quench singlet oxygen and react with a variety of radical species may help to reduce oxidative stress in humans. So, it may help protect against diseases like heart disease and cancer [185]. Leaves and fruits extracts of Celtis plants display antioxidant activities in various tests (Table 6).

In a 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) scavenging test, methanolic extract of C. africana stems showed better antioxidant

activity than leaves [186]. Another hackberry (C. australis) showed different antioxidant properties at DPPH, and ferric reducing antioxidant power assay (FRAP) based on their different genotpes. The varying antioxidant potential estimated using FRAP and DPPH

tests was 44.35–117.87 mg Fe2+/100 g and 14.12–88.24 %, respectively [110]. Furthermore, Synergism activity is also noticed in the

Celtis genus. For instance, the n-butanol fraction of C. africana aerial parts exhibited an IC₅₀ value of 40.5 μM, which is better than the other isolated compounds of this fraction >42 μM [123]. Water extract of C. tournefortii fruit showed more efficacious in hydroxyl radical (OH—) scavenging test than the standard butylated hydroxytoluene (BHT) [33]. Also, hydroalcoholic extracts of C. iguanaea

leaves showed antioxidant activity in a rat model by lowering the levels of thiobarbituric acid reactive substances (TBARS) (byproducts of lipid peroxidation) in the plasma and raising the levels of nonprotein thiols (CI-600) [121].

Almost all investigated Celtis plants contain a variety of flavonoids, including flavanol, flavone, isoflavone, flavonol, and flava- nonol, which have been known for their antioxidant activity due to their ability to act as hydrogen donors as well as reducing agents [188]. Flavonoids suppress the enzymes that produce superoxide anions, such as protein Kinase-C and xanthine oxidase. They can also inhibit microsomal monooxygenase, cyclooxygenase, mitochondrial succinoxidase, lipoxygenase, glutathione S-transferase, and nicotinamide adenine dinucleotide oxidase, all of which are involved in the generation of ROS. Furthermore, flavonoids effectively chelate trace metals that are needed in oxygen metabolism [189]. Three flavanols, compounds 59, 61, and 62, are reported from the Celtis plants (Table 3), where compounds 59 and 62 demonstrated similar antioxidant properties in the DPPH scavenging test (nearly

Table 6

Antioxidant properties of various extractives of Celtis genus.

Species Part

Extract

In vitro/ In vivo

Key findings Positive

control/ Standard

Ref no.

C. africana Aerial parts

Ethanol extract (n-butanol fraction)

In vitro Showed anti-oxidant activity while IC₅₀ value was 40.5 μM (DPPH scavenging test). That was better than the other isolated compounds > 42 μM.

Maybe it’s a synergism effect of isolated compounds

from this extract

BHA [123]

C. africana Leaves and stems

Methanol extract In vitro At 0.1 mg/ml concentration, stem showed better

activity than leaves (DPPH testing). It is less effective than the standard ascorbic acid and butylated hydroxytoluene (BHT).

Stems > Leaves

Ascorbic acid, BHT

[186]

C. australis Leaves Hydroalcoholic extract In vitro Comparison to the Ascorbic acid (IC₅₀ = 14.3 μg/ml), it

showed lower activity (IC₅₀ = 80.5 μg/ml) in DPPH

scavenging test.

Ascorbic acid [187]

C. eriocarpa Leaves Methanol extracts and sub

fraction

In vitro Ethyl acetate fraction showed greater activity than others including hexane, chloroform, aqueous fractions and methanol extracts (DPPH testing).

Ethyl acetate fractions (EC₅₀ = 324.81 μg/ml) >

methanol extracts (EC₅₀ = 593.68 μg/ml) > chloroform fractions (EC₅₀ = 1058.18 μg/ml) > aqueous fractions (EC₅₀ = 1155.0 μg/ml) > hexane fractions (EC₅₀ = 2981.03 μg/ml).

Ascorbic acid [118]

C. iguanaea Leaves Hydroalcoholic extract In vivo Activity was observed in rats’ plasma by the decrease of

TBARS (Thio-barbituric acid reactive substances) and an increase in nonprotein thiol levels (CI-600).

Simvastatin [121]

C. pallida Leaves Methanol, methanol:

water (80:20), and acetone extract

In vitro In the DPPH scavenging test, acetone extract showed better activity than other two including methanol, and methanol: water (80:20).

acetone > methanol > methanol: water (80:20)

BHA,

α-tocopherol

[117]

C. tournefortii Fruits Water, ethanol and

methanol extracts

In vitro In the DPPH radical scavenging testing, activity was lower than standard BHT. However, in the OH— scavenging testing fruits water extract (84.12 %) exhibited higher antioxidant activity than BHT (75.77

%).

BHT [33]

C. zenkeri Leaves and stem barks

Essential oils In vitro At 250 μg/ml, leaves showed tremendous antioxidant

activity compared to standard ascorbic acid and BHA, while being higher than α-tocopherol (DPPH testing). Stem barks showed the same potent activity as

standards (ascorbic acid and BHA) at any concentration, more than α-tocopherol.

Ascorbic acid and BHA

[99]

Table 7

Antioxidant properties of the new phytoconstituents of Celtis genus.

Standard

Comp. Number	Plants	Invitro/ In vivo	Key findings	Positive control/	Ref. no
Compound 138	C. australis	In vitro	In the DPPH scavenging test, the IC₅₀ value was 8.2 μg/	BHT	[127]

ml, while the BHT IC₅₀ was 12.0 μg/ml.

Compound 131 C. tessmannii In vitro In the DPPH radical scavenging test, compound 53 was

better antioxidants than the standard.

BHA [97]

Compound 81 C. australia &

C. occidentalis

In vitro Showed greater activity against superoxide radical (induced by xanthine oxidase) as well as DPPH radical scavenging testing than the standard.

α-tocopherol, and BHT

[52]

Compound 8, C. africana In vitro In the DPPH scavenging test, compound 6 is more active BHA [102]

Compound 10,

Compound 6

Compound 6, compound 10,

compound 9, compound 7,

compound 4, compound 8

than others two compounds. Compound 6 and compound 10, were better than standard BHA (26.3 μm and 33.2 μm, respectively).

Compound 6 > compound 10 > compound 8

C. occidentalis In vitro In the DPPH scavenging testing, compound 6 and

10showed remarkable antioxidants activity. Compound 6 > compound 10 > compound 9 >

compound 7 > compound 4 > compound 8

Caffeic acid (IC₅₀

= 4.6 ± 0.3)

[100]

Compound 138, compound

141, compound 125

C. adolphi-friderici In vitro In the DPPH scavenging test, compound 125 showed

tremendous activity compound 141, and compound 138. While all compounds demonstrated good antioxidant as well as better than the standard BHA

Compound 125 > compound 141 > compound 138 >

standard BHA.

BHA [103]

Note: Compound number indicates the serial number of the compounds displayed in Table 3.

80 % effective), while compound 61 was greater than them (85 % effective). But low-density lipoprotein (LDL) oxidation and FRAPassays showed that compounds 59 and 61 were equally effective (Table 7) [190].

Compound 104, a flavonol glycoside, is isolated from four different Celtis species (C. australis, C. tournefortii, C. occidentalis, and

C. iguanaea) (Table 7), and exhibits a variety of protective actions via an antioxidant mechanism. For example, it acts as a ROS scavenger where it increases glutathione production as well as improves cellular oxidative defense mechanisms by upregulating numerous antioxidant enzymes, including catalase and superoxide dismutase [191]. Additionally, compound 104 inhibits xanthine oxidase, which is also responsible for the production of ROS [191]. It also displays several neuroprotective activities in various in vitro and in vivo studies, through the reduction of ROS, lipid peroxidation, and iNOS [191]. Another apigenin flavone glycoside of the Celtis

genus, compound 114 and its various derivatives (Table 3) also have remarkable antioxidant as well as protective activity where it reduces the growth of lipid peroxidation, nitrite levels, and neuronal degeneration. It recovers the acetylcholinesterase–monoamine enzyme to its normal range and reduces the expression of mRNA of the metabotropic glutamate receptor 1, N-methyl– D-aspartate-receptor, and metabotropic glutamate 5 [192]. Another study of compound 114 (15 mg/kg, i. v.) showed that it improved

the neurological dysfunction in cerebral ischemia/reperfusion by boosting extracellular signal-regulated kinase ½ and BCL-2 protein levels in the cortex and hippocampus while diminishing BCL-2 associated X protein expression, jun N-terminal kinases, and p38 phosphorylation [193].

Because of having conjugated double bonds, terpenoid compounds have the ability to quench singlet oxygen, hydrogen or electron transfer. Such as isolated terpenoids of C. australis fruits, compound 83 showed greater antioxidant activity than compound 82 due to the presence of additional double bonds in compound 83 [185]. Along with oxygen radicals, terpenoids also scavenge several radicals. Compound 82, for instance, scavenges sulfur radicals, whereas compound 84 scavenges sulfonyl, nitrogen, and glutathione radicals

[185]. Tocopherols (compounds 85–88) can move hydrogen atoms from one molecule to another, which changes lipids and peroxyl radicals into more stable substances [194].

Other uses

Along with traditional and pharmacological uses, Celtis plants are also known for their decorative [195], furniture, millwork, and box manufacturing purposes [195,196]. Apart from decorative use, C. africana wood is used for flooring, construction, fuel, and charcoal manufacturing [27]. C. occidentalis roots are used to make dye [197], while the bark of C. australis is used to make yellow dye [198]. Furthermore, the woods of C. australis are used as fuel [199], agriculture equipment, and handle manufacturing [88]. Malleable thin shoots are used as walking sticks [197]. The timber of C. tetranda is strong, and durable and is used for manufacturing handle ores as well as fuel [199]. Roots of C. pallida are much strong to use in erosion problems [200]. However, the timber of C. laevigata and

C. pallida is not good enough. They are used only for fencing and fuel [199,201,202].

Limitations

The review could be more flawless. The specified phytoconstituents of the genus or delve into their intricate mechanisms of action were not thoroughly examined primarily due to insufficient evidence regarding precise mechanistic details. In addition, the review

lacks the crucial ethnopharmacological information. The ethnopharmacology section would benefit from enhancements by incor- porating specific criteria for interpreting ethnobotanical data. This could involve utilizing qualitative citation metrics like Relative Frequency Citation (RFC), Fidelity Level (FL), Relative Importance (RI), and Frequency Index (FI). However, since the article is pri- marily a narrative review, its main emphasis lies in presenting the current understanding of the ethnopharmacological and phyto- pharmacological significance of the Celtis genus. This focus is intended to facilitate future research and the acquisition of data for characterizing the genus and exploring its medicinal uses, with the potential to expedite the discovery of novel bioactive compounds.

Conclusion and futuristic prospects

Numerous findings show that plants of the Celtis genus have remarkable ethnopharmacological properties, thanks to their bio- logically active compounds. The three most investigated species, C. africana, C. australis, and C. tournefortii, have antibacterial, antioxidant, anticancer, and anti-inflammatory properties. Phytochemical studies revealed that the primary constituents occurring in this genus are amides, organic acids (phenolic acids, hydroxycinnamic acids, fatty acids, and aliphatic carboxylic acids), terpenoids (diterpenoids, triterpenoids, tocopherols, and carotenoids), flavonoids (flavanol, flavone, flavonol, and their glycosides), and esters (fatty acid esters).

Despite the important biological activities (antimicrobial, anticancer, and overall urease inhibition activities) of the genus Celtis, thanks to their potential new therapeutic molecules, this have not fully confirmed them because the studies were not fully established with scrutiny. Moreover, preliminary research has been limited to a few animal trials and is not widely accepted because it may behave differently in extensive studies.

To promote the therapeutic active compounds and as nutraceuticals of the Celtis genus, the research community may take some following steps.

Because the activity of bioactive compounds in the Celtis genus is connected to their ethnopharmacological activity, retrace and organize traditional information about the Celtis species to understand how effective bioactive molecules may have been discovered.
Further phytochemical analysis is needed to isolate compounds from the bio-active extracts and bioassay tests of the isolated compounds are also needed for the determination of the responsible phytochemicals. For example, the extracts C. australis and

C. africana showed some hope of having effective antimicrobial agents.

Designing a new pathway to collect or synthesize target molecules noticed in Table 5 may lead to finding a novel medicinal molecule.
In addition to the study of pharmacological activity, a pharmacokinetic study to evaluate the absorption, metabolism, distri- bution, and elimination of Celtis extract and its bioactive phytoconstituents is required.
An accurate toxicology and dose-response graph are needed to indicate the therapeutic range which was missed in the maximum study.
Clinical trials are required to evaluate the further biological consequences of these substances that have already been examined in vitro and in vivo.
The bioactive agents’ safety and efficacy and the potential pathways of protection must also be evaluated before introducing

such molecules for further studies in human and animals.

Because of the up to date comprehensive information on the Celtis genus’ ethnopharmacological to potent bioactive molecules and phytochemistry, as well as the future prospects of the scope of Celtis genus research, this review article will be helpful to those who have an interest in the Celtis genus especially for its important ethnopharmacology and bioactive molecules.

Data availability statement

All the data involved in the review are explained in the manuscript.

CRediT authorship contribution statement

Md Abdus Samadd: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Vali- dation, Visualization, Writing – original draft. Md Jamal Hossain: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. Miss Sharmin Zahan: Investigation, Methodology, Validation, Visualization, Writing – review & editing. Md Monirul Islam: Resources, Software, Validation, Visualization, Writing – review & editing. Mohammad A. Rashid: Investigation, Methodology,

Supervision, Validation, Visualization, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Abbreviations

Introduction

Methods

Botany

Table 2

Ethnopharmacology

Phytochemistry

Table 3

Amides

Organic acids

Terpenoids

Biological activities

Table 4

Table 5

Antioxidant properties

Table 6

Table 7

Other uses

Limitations

Conclusion and futuristic prospects

Data availability statement

CRediT authorship contribution statement

Declaration of competing interest

References

Chemical Profiling and Antioxidant, Anti-Inflammatory,

The Future of AI in Business SECTORS : How Automation is Reshaping Industries.

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A comprehensive account on ethnobotany, phytochemistry and pharmacological insights of genus Celtis.

Abbreviations

Introduction

Methods

Botany

Table 2

Ethnopharmacology

Phytochemistry

Table 3

Amides

Organic acids

Terpenoids

Biological activities

Table 4

Table 5

Antioxidant properties

Table 6

Table 7

Other uses

Limitations

Conclusion and futuristic prospects

Data availability statement

CRediT authorship contribution statement

Declaration of competing interest

References

Chemical Profiling and Antioxidant, Anti-Inflammatory,

The Future of AI in Business SECTORS : How Automation is Reshaping Industries.

Leave a Comment Cancel reply