ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 A Comprehensive Review on Genus Zygophyllum Enas M. Shawky1, Nagwan M. Gabr2*, Mohamed R. Elgindi2, Reham H. Mekky1 1 Pharmacognosy Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt 2 Pharmacognosy Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt *Corresponding author: Nagwan M. Gabr, Pharmacognosy Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt. Tel.: +201023312245 E-mail address: drnagwangabr@gmail.com Submitted on: 16-10-2018; Revised on: 11-11-2018; Accepted on: 07-01-2019 ABSTRACT Objectives: This study aimed to make a broad review of the chemical constituents and biological activities of genus Zygophyllum. Methods: This review covers the peer reviewed articles between 1977 and August, 2018, retrieved from PubMed, Science Direct, Sci-Hub, Springer and Wikipedia Results: In traditional medicine, plants of genus Zygophyllum have been employed and utilized as anti-rheumatic, anti-gout, antidiabetic, anti-hyperlipidemic, antimicrobial, antioxidant, antihypertensive, antiseptic, anti-eczema and antidiarrheal. Zygophyllum species have been phytochemically studied leading to the identification of various classes of compounds including triterpenes, flavonoids, saponins, sterols, simple phenolic compounds, and esters. Biological studies on Zygophyllum species have also indicated various bioactive potentials including antioxidant, antidiabetic, antimicrobial antitumor and anti-inflammatory effects. The reported medicinal Zygophyllum species were selected and summarized on basis of their; geographical distribution, traditional uses, chemical constituents and biological activities. Conclusion: It would therefore be important to extensively investigate their phytochemicals and pharmacologically determine their activities for future drug discovery and development. Keywords: Biological activities; Chemical constituents; Geographical distribution; Traditional uses; Zygophyllum INTRODUCTION Zygophyllaceae (Caltrop family) is a family of approximately 25 genera and 240 species adapted to semi desert and Mediterranean climates1. Species belonging to genus Zygophyllum represent a group of succulent plants that are drought resistant and/or salt tolerant, living under severe, dry climatic conditions2. Moreover, it is recorded by many authors as one of the important components of the desert vegetation3. The abundance of species related to this genus could be attributed to their high tolerance to environmental stresses as well as to their unpalatability4. The growth and distribution of Zygophyllum species are attributed to their dependence on the chemical nature of the soil of their habitats5. The genus Zygophyllum consist of 100 species, distributed in desert and steppe habitats from the Mediterranean to central Asia, South Africa and Australia4. Most of plants of genus Zygophyllum are small perennial herbs with fleshy leaves and flowers, as in cases of Z. simplex, Z. cocceniem, Z. album, Z. fabago and Z. dumosum6. Nine species are widespread in the deserts and salt marshes in Egypt and Sinai Peninsula5. They have been utilized in traditional medicine for various ailments, such as treatment of rheumatism, gout, diabetes, asthma, hypertension, dysmenorrhea, as well as fungal infection7-11. Biological studies on Zygophyllum species have indicated significant antioxidant, antidiabetic, antitumor, antimicrobial and antiinflammatory activities12-17. Such activities were contributed to their phytochemical constituents. Various classes of compounds including triterpenes, flavonoids, saponins, sterols, phenolic, essential oils and esters have been isolated from different Zygophyllum species18-23. http://aprh.journals.ekb.eg/ 1 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 Table 1. Reported Zygophyllum species, their distribution and traditional uses Zygophyllum species Distribution Traditional use Z. aeyptium18,24 Z. album8 Z. atriplicoides (Synonym: Z. eurypterum)25 Z. coccienium9,26 Z. cornutum10 Egypt, Tunisia, Cyprus Egypt, Algeria, Tunisia Pakistan Egypt, Kuwait, Saudi Arabia Algeria Rheumatism, gout, asthma and hypertension Diabetes, dermatitis, spasms and dysmenorrheal Alzheimer’s disease and brain diseases with deficiency in cholinergic function Gout, Rheumatic pain and hypertension Diabetes, hypertension and dermatitis Z. decumbens27 Z. dumosum23,28,29 Z. fabago19 Egypt, Syria, Sudan Egypt China, Spain, Turkey, Iran, Kazakhstan and Iraq Hypotension, fever and GIT spasm Rheumatism, gout, asthma and hypertension Fungal infections, Parasitic worms, constipation, product cough, inflammation, and asthma Z. gaetulum11 Morocco Z. geslini12 Z. hamiense30 Z. macropodum31 Algeria Deserts of Asia and Africa China GIT spasms, hyperglycemia accompanying diabetes and eczema Hyperglycemia accompanying diabetes As hepato-protective Pain and inflammation Z. melongena20 Mongolia Snake poisoning (as it inhibits of the snake venom phosphodiesterase) Z. qatarense13 Z. simplex32 Iran Egypt, Saudi Arabia, India and Pakistan Fungal infections Glaucoma, inflammation, fungal infections and hyperglycemia accompanying diabetes antidiabetic, antimicrobial, antitumor and other effects are illustrated in Table 3. MATERIALS AND METHODS This review covers the peer reviewed articles between 1977 and August, 2018, retrieved from PubMed, Science Direct, Sci-Hub, Springer and Wikipedia. RESULTS AND DISCUSSION Distribution and traditional use Data reported on Zygophyllum species used mostly in folk medicine is summarized in Table 1 according to their geographical distribution and traditional uses. Phytochemical constituents: It was reported that the plants belonging to genus Zygophyllum are rich in essential oil, sterols, triterpenes, phenolic compounds, flavonoids and saponins. The previously isolated compounds from reported Zygophyllum species are labeled together with their chemical classes in Table 2 and their chemical structures are shown below. Biological studies Reported biological activities of various Zygophyllum species included antioxidants, Antioxidant activity One of the most remarkable effects of the members of Zygophyllum genus is their antioxidant activity (Table 3). Such activity is attributed to the presence of the phenolic compounds as reported in cases of Z. cornutum10, Z. album6,8,38, Z. cocceniem7, Z. hamiense28, Z. simplex16,64 and Z. fabago46. The most active extracts with the highest antioxidant activity; were those of the alcohol (methanol and ethanol) ones followed by dichloromethane extracts while the hexane extracts were poorly active6. Consequently, Zygophyllum genus represents an important economical source of antioxidant agents. Antidiabetic activity The antidiabetic activity of members of the Zygophyllum genus have been reported in several studies (Table 3). The aqueous and butanol extract of Z. gaetulum in alloxan-induced diabetic rats (n=6) caused a continuous marked reduction of blood glucose levels particularly 6–9 hr {hours} after treatment. Significant difference was observed; (P˂0.001) (52.82±6.54; 69.80± 3.86, respectively). The blood glucose level fell rapidly from 333±47 mg/dl at fasting to 205±34 http://aprh.journals.ekb.eg/ 2 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 Table 2. Reported Zygophyllum species; isolated compounds and chemical classes Compound no. Chemical classes Isorhamnetin Isorhamnetin-3-O-β-D-glucoside Isorhamnetin-3-O-β galactopyranoside Isorhamnetin-3-O- β –rutinoside Quercetin-3-O-β-glucopyranoside (Isoquercitin) Kaempferol Gentisic acid 1 2 3 4 11 12 17 β –sitosterol Stigmasterol Ursolic acid Oleanolic acid quinovic acid 3-α-L-rhamnoside Malvidin 3-rhamnoside Linalool Tricosane Camphor 18 20 21 22 34 60 61 63 64 α-Terpineol Carvone Harmine (β-carboline alkaloid) β –amyrin Isorhamnetin-3-O- β –rutinoside Quinovic acid-3-O-β-D-glucopyranoside Quinovic acid-3-O-β-D-2-O-sulphonylquinovopyranoside Quinovic acid-3-O-β-D-glucopyranosyl-(28→1)-β-Dglucopyranosyl ester Quinovic acid-3-O-β-D-quinovopyranosyl-(28→1)-β-Dglucopyranosyl ester Quinovic acid-3-[β-D-xylopyranosyl (1→2) quinovopyranosyl]-(28→1)- β-D-glucopyranosyl ester (7R,8S,8′S)-4, 9, 4′-trihydroxy-3, 3′-dimethoxy-4′sulfonyl-7, 9′-epoxylignan Quinovic acid-3-O-β-D-quinovopyranoside Quinovic acid-3-O-β-D-quinovopyranosyl-(27 → 1)-β-Dglucopyranosyl ester 65 66 67 68 4 32 33 36 Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Hydroquinone carboxylic acid Sterols Sterols Triterpenoid Triterpenoid Triterpenoid Anthocyanins Terpene alcohol Acyclic hydrocarbons Bicyclic monoterpene ketone Monoterpene alcohol Monoterpene Alkaloids Triterpenoid Flavonoids Triterpenoid Triterpenoid Triterpenoid 38 Triterpenoid 52 Triterpenoid 57 Lignans 69 70 Triterpenoid Triterpenoid Z. atriplicoides (Synonym: Z. eurypterum)25,40 β-Sitosterol-3-O-β-D-glucopyranoside Atricarpan A Atricarpan B Atricarpan C Atricarpan D Atriplicosaponin B 19 24 25 26 27 37 Sterols Isoflavonoids Isoflavonoids Isoflavonoids Isoflavonoids Triterpenoid saponins Z. atriplicoides25,40 Atriplicosaponin A 56 Triterpenoid saponins Z. coccienium6,23,36,41,42 Isorhamnetin-3-O- β –rutinoside 5,6,7,8,4`penta hydroxy flavone 7 -β - D glucoside β –sitosterol β-Sitosterol-3-O-β-D-glucopyranoside Stigmasterol 4 15 18 19 20 Flavonoids Flavonoids Sterols Sterols Sterols Ursolic acid Oleanolic acid Zygophylloside S 3-O-[β-D-glucopyranosyl]-quinovic acid 3-O-[β-D-(2-O-sulphonyl)quinovopyranosyl] quinovic acid 3-O-[β-D-glucopyranosyl] quinovic acid-28-O-β-Dglucopyranosyl ester 21 22 31 32 33 Triterpenoid Triterpenoid Triterpenoid saponins Triterpenoid Triterpenoid 36 Triterpenoid Zygophyllum species Z. album6,14,23,33-39 Z. aeyptium18,24 Identified compounds http://aprh.journals.ekb.eg/ 3 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Z. cornutum 6,43 Z. decumbens6,27 Z. dumosum6,23,28,36 Z. eichwaldii44 Z. fabago19,21,45-48 Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 3-O-[β-D-quinovopyranosyl] quinovic acid-28-O-β-D-glucopyranosyl ester 3-O-[α-L-arabinopyranosyl-( 1→2)-β-D-quinovopyranosyl] quinovic acid 3-O[α-L-arabinopyranosyl-(1→2)-β-D-quinovopyranosyl] quinovic acid-28-O-β-D-glucopyranosyl ester 2-(3, 4-Dihydroxyphenyl)-3, 5, 7-trihydroxy-6-methoxy-4benzopyrone (Patuletin) Isorhamnetin-3-O- β –rutinoside 38 Triterpenoid 39 Triterpenoid 40 Triterpenoid 59 Flavonoids 4 Flavonoids β –sitosterol 18 Sterols Isorhamnetin-3-O-β-D-glucoside 2 Flavonoids Isorhamnetin-3-O- β –rutinoside 4 Flavonoids Isorhamnetin 3-(4''-sulfatorutinoside) Isorhamnetin 3-[6''-(2(E) butenoyl)-glucoside] Isorhamnetin-3-O-β-glucopyranoside-7-O-αrhamnopyranoside Quercetin Rutin Quercetin-3,7-di-O-β-glucopyranoside Quercetin-3-O-β-glucopyranoside (Isoquercitin) Kaempferol kaempferol-3-O- β-rutinoside (Nicotiflorin) Ursolic acid Oleanolic acid 3-O-[β-D-glucopyranosyl]-quinovic acid 3-O-[β-D-2-O-sulphonyl quinovopyranosyl]-quinovic acid-27-O-[β-D-glucopyranosyl] ester 5 6 7 Flavonoids Flavonoids Flavonoids 8 9 10 11 12 13 21 22 32 35 Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Triterpenoid Triterpenoid Triterpenoid Triterpenoid Pomolic acid 3-O-α-L-arabinoside 28 Triterpenoid saponins 28-O- β -D-glucopyranosyl ester of pomolic acid 3-O- β D-2-O-sulfonyl-galactopyranoside. 28-O- β- D- glucopyranosyl ester of pomolic acid-3-O-αL-arabinoside 29 Triterpenoid saponins 30 Triterpenoid saponins Isorhamnetin β –sitosterol β-Sitosterol-3-O-β-D-glucopyranoside 3-O-[β-D-glucopyranosyl] quinovic acid-28-O-β-Dglucopyranosyl ester 3-O-[β-D-quinovopyranosyl] quinovic acid-28-O-β-D-glucopyranosyl ester Zygophyloside E Zygophylosides O Zygophylosides P 3β,4α -3,23,30-trihydroxyurs-20-en-28-al 3,23-di(sulfate) sodium salt 3β,4α -3,23,28-trihydroxyurs-20-en-30-yl β-Dglucopyranoside 3,23-di(sulfate) sodium salt Zygofaboside A Eicosane 1-hydroxyhinesol Hinesol Atractylenolactam β-eudesmol 5-α-hydroperoxy-β-eudesmol 11-hydroxy-valenc-1(10)-en-2-one Pubinernoid A 1 18 19 36 Flavonoids Sterols Sterols Triterpenoid 38 Triterpenoid 44 48 49 53 Triterpenoid saponins Triterpenoid saponins Triterpenoid saponins Triterpenoid 54 Triterpenoid 55 62 72 71 73 74 75 76 77 Triterpenoid saponins Alkane Sesquiterpenoid Sesquiterpenoid Sesquiterpenoid Sesquiterpenoid Sesquiterpenoid Ketone Sesquiterpenoid http://aprh.journals.ekb.eg/ 4 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Z. gaetulum 49,50 Z. geslini51 Z. melongena6,20 Z. propinquum52 Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 (6S,7E)-6-hydroxy-4,7-megastigmadien-3,9-dione (3S,5R, 6S, 7E)-3, 5, 6-trihydroxy-7-megastigmen-9-one (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one Blumenol A (S)-3-hydroxy-beta-ionone 3-hydroxy-5-α-6-α-epoxy-beta-ionone Z-lanceol acetate (E, Z)-geranyl linalool β-bisabolenol Menthol Geranyl valerate (E)-β-damascenone 78 79 80 81 82 83 84 85 86 87 88 89 α-inone butylated hydroxyl toluene (E)-2-hexen-1-ol Phytol Octadecane σ-deca lactone Zygocaperoside 91 92 93 94 95 105 58 Sesquiterpenoid Sesquiterpenoid Sesquiterpenoid Carotenoids Ketone Ketone Sesquiterpene Terpene alcohol Sesquiterpene Alcohols Esters Cyclic monoterpene ketone Ketones Phenols Alcohols Acyclic diterpene Alkane Ketones Triterpenoid saponins 3-O-[β-D-glucopyranosyl] quinovic acid-28-O-β-Dglucopyranosyl ester Zygophyloside G Zygophyloside E Zygophyloside I Zygophyloside L Zygophyloside M Linalool Eicosane Camphor 36 Triterpenoid 43 44 45 46 47 61 62 64 α-Terpineol 3β- O- α- L rhamnopyranosyl (1→2) - α- Larabinopyranosyl – (1→2) – β – D- glucopyranosyl) urs 20(21)-en-28-oic acid 28-O-[ β – D-glucopyranosyl] ester 3β- O- β- D-quinovopyranosyl – 27 – nor – olean – 12- en – 28 – oic acid 28 - O- β – D-glucopyranosyl ester 3β – O- α- L rhamnopyranosyl (1→2) - α- Larabinopyranosyl – (1→2) – β – D- glucopyranosylurs 20(21)-en-28-oic acid 28-O-[β – D-2-Osulphonylglucopyranosyl] ester 65 96 Triterpenoid saponins Triterpenoid saponins Triterpenoid saponins Triterpenoid saponins Triterpenoid saponins Terpene alcohol Alkane Bicyclic monoterpene ketone Monoterpene Alcohol Triterpenoid 97 Triterpenoid 3-O-[α-L-arabinopyranosyl-(1→2)-β-D-glucopyranosyl] quinovic acid 28(β-D-glucopyranosyl) ester 3-O-[β-D-(2-O-sulphonyl) glucopyranosyl] quinovic acid (3β)-3-{[6-deoxy-α-L-mannopyranosyl-(1→2)-α-Larabinopyranosyl (1→2)-β-D-glucopyranurosonyl] oxy} urs-20-en-28-oic acid 28-(2-O-sulfo-β-D-glucopyranosyl) ester 3β-3-[(2-O-sulfo-β-D-glucopyranurosonyl) oxy]-urs-20en-28-oic acid 28-(2-O-sulfo-β-D-glucopyranosyl] ester. kaempferol 3-O-β-D-glucoside 41 Triterpenoid 42 50 Triterpenoid Triterpenoid 51 Triterpenoid 14 Flavonoids D-pinitol 3-O-[β-D-glucopyranosyl]-quinovic acid 3-O-[β-D-glucopyranosyl] quinovic acid-28-O-β-Dglucopyranosyl ester 3-O-[β-D-2-O-sulphonyl-quinovopyranosyl]-quinovic acid. 3-O-[β-D-2-O-sulphonyl-quinovopyranosyl]-quinovic acid-27-O-O-[β-D-glucopyrosyl] ester 23 32 36 Cyclic polyol Triterpenoid Triterpenoid 33 Triterpenoid 35 Triterpenoid http://aprh.journals.ekb.eg/ 5 Triterpenoid ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 Z. simplex 6,22,53,54 Isorhamnetin Isorhamnetin-3-O-β-D-glucoside Isorhamnetin-3-O- β –rutinoside Isorhamnetin 3-[6ʺ-(2(E) butenoyl) glucoside] Isoquercetin kaempferol-3-O- β-rutinoside (Nicotiflorin) Luteolin-7- O-β-D-glucoside Gentisic acid 1 2 4 6 11 13 16 17 Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Flavonoids Hydroquinone carboxylic acid Z. simplex 6,22,53,54 β –sitosterol β-sitosterol-3-O-β-D-glucoside Ursolic acid Oleanolic acid Quinovic acid 3-α-L-rhamnoside Stigmast-3,6-dione Isorhamnetin-3, 7-diglucoside Isorhamnetin-3-O- β – D- (6'-malonyl) glucoside Quercetin-3-O-(6''-malonyl) glucoside P-hydroxy acetophenone Vanillic acid Ferulic acid Androsin 18 19 21 22 34 90 98 99 100 101 102 103 104 Sterols Sterols Triterpenoid Triterpenoid Triterpenoid Sterols Flavonoids Flavonoids Flavonoids Phenols Dihydroxy benzoic acid Hydroxyl cinnamic acid Aromatic ketone mg/dl at 3 hr and to 182±34 mg/dl at 6 hr11,61. In another study , the ethanol extract of Z. album to diabetic mice significantly decreased the level of blood glucose and increased plasma insulin gain to near normal level by (p < 0.05, post hoc Dunnett’s test)14,35,56. The ethanol extract of Z. album with IC50 {concentration of 50% inhibition} value (43.48 μg/ml) evidenced a better pancreatic α-amylase inhibition than that of the other fractions. Meanwhile, it was observed that the pancreatic α-amylase inhibitory activities increased in the order of hexane fraction, butanol fraction & ethanol extract14. The pancreatic and serum α-amylase activities of essential oil of Z. album in treated diabetic rats were noted to undertake considerable reductions of 43 and 38%, respectively35. The IC50 value of essential oil of Z. album against αamylase was 43.17 μg/ml and that against pancreatic lipase was 85.95 μg/ml56. Also, diabetic rats treated with methanol extract of Z. cornutum, a significant decrease of glycaemia was noted from the second week and the value recorded after six weeks was 145 ± 12.3 mg/dL. The hypoglycemic effect of methanol extract of Z. cornutum may be attributed to its saponins content58. Antimicrobial and antifungal activities One of the most attracting activities of the extracts of genus Zygophyllum is the antimicrobial activity against gram positive, gram negative bacteria and several fungi (Table 3). A good example is the effectiveness of the aqueous methanol roots extracts of Z. dumosum, Z. coccineum and Z. qatarense on inhibition of the spore germination of Verticillium alboatrum and Fusarium oxysporum13,15,29. The shoot extract using the same solvent showed variable toxicity among the extracted Zygophyllum13,15,29 such that the extracts of Z. dumosum were suppressive only to Fusarium oxysporum29. On the other hand, the extract of Z. coccineum was inhibitory only to Verticillium albo-atrum15. In another study, the ethanol extract of Z. coccineum has antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, Microsporum canis and Trichophyton mentagrophytes57. The antifungal activity of the isolated compounds of Z. coccineum was investigated against Colletotrichum acutatum, Colletotrichum fragariae, Colletotrichum gloeosporioides, Botrytis cinerea, Phomopsis obscurans, Phomopsis viticola, and Fusarium oxysporum. The observed results were recorded against Phomopsis viticola after 144 hr exposure57. The methanol extract of Z. simplex showed marked antimicrobial activity against seven standard bacteria (Proteus vulgaris, Escherichia coli, Bacillus cereus, Salmonella typhi, Klebsiella pneumonia, Pseudomonas aeruginosa and Staphylococcus aureus) and one standard fungus (Candida albicans)17. Also, the nanoparticles of the methanol extract of Z. qatarense leaf exhibited antifungal activity against Aspergillus nigra and Penicillium digitatum was evaluated by standard disk diffusion, the results showed minimum inhibitory concentration {MIC} and minimum fungal concentration {MFC} against Aspergillus nigra equal to 16 and 128 μg/ml respectively and against Penicillium digitatum equal to 32 and 64 μg/ml respectively13. Leaves’, seeds’ and roots’ extract of Z. fabago were evaluated evaluated their antimicrobial activities against http://aprh.journals.ekb.eg/ 6 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 Table 3. Reported Zygophyllum species; their biological activities Zygophyllum species Biological activities Z. album Antioxidant6,8,38 Anti-acetylcholinesterase8 Antidiabetic35,55,56 Antiinflammatory14 Antihyperlipidemic56 Anti-hypertensive14 Weight lowering37 Z. cocceniem Antioxidant7 Anti-hypertensive9 Antimicrobial and antifungal15,57 Cytotoxic activity15 Antioxidant10 Antidiabetic58 Antimicrobial and antifungal29 Antioxidant46 Antimicrobial and antifungal59 Urease inhibitor60 Antidiabetic11,61 Antispasmodic62 Hepatoprotective11 Antidiabetic12,63 Antioxidant 28 Analgesic and anti-inflammatory31 Antimicrobial & antifungal13 Antioxidant16,64 Anti-inflammatory64,65 Analgesic65 Antimicrobial and antifungal17 Antihyperlipidemic66 Cytotoxic activity6 Z. cornutum Z. dumosum Z. fabago Z. gaetulum Z. gaetulum Z. geslini Z. hamiense Z. macropodum Z. qatarense Z. simplex Bacillus subtilis showing MIC equal to 10, 1, 20 mg/ml respectively, Staphylococcus aureus showing MIC equal to 20, 1, 30 mg/ml respectively, Escherichia coli showing MIC equal to 30, 10, 50 mg/ml respectively, Pseudomonas aeruginosa MIC were 50, 20, 30 mg/ml respectively and Candida albicans, which was the most resistant for all extracts59. The ethyl acetate extract of Z. cocceniem showed antibacterial activities against; Pseudomonas aeruginosa with inhibition zone 20 mm, Fusarium moniliforme with inhibition zone 22 mm, and Klebsiella pneumonia showed inhibition zone 22 mm57. Cytotoxic activity Recent study showed that the cytotoxic activity of dichloromethane fraction of Z. simplex showed powerful effect against cancer cell lines; Human lung carcinoma cells {A-549} and Human colon adenocarcinoma cells {DLD-1} with important IC50 values of 37 and 48 µg/ml, respectively6. Also Z. coccinium extracts showed maximum cytotoxic activity of the acetone extract against Human cervix epithelioid carcinoma {HeLa cell line}, whereas methanol extract showed maximum cytotoxic activity on breast cancer cell line {MCF-7 cell line} with cell line viability 13.36 and 35.19%.15 Other effects Other activities have also been reported on members of genus Zygophyllum Table 3. Antiinflammatory activity best results were recorded for Z. album and measured by serum level of C-reactive protein and pancreatic tumor necrosis factor were decreased by 59 % and 64 %, respectively14. Also, the analgesic activity was reported for the ethanol extract of Z. macropodum (ZME) in acetic acid induced writhing method. The inhibition percentages of ZME 100, 300, and 600 mg/kg were 8.7%, 24.9%, 51.3%, respectively having significant inhibitory effect on increased vascular permeability induced by acetic acid in mice (P < 0.05 and P < 0.001, respectively) compared to normal control31. http://aprh.journals.ekb.eg/ 7 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 R1 H O-β-D-glucoside O-β galactopyranoside O- β –rutinoside (4''-sulfatorutinoside) 6”-(2(E) butenoyl) glucoside] O-β-glucopyranoside O-β-D-glucoside O- β – D- (6'-malonyl)glucoside R1 H O- β –rutinoside O-β-glucopyranoside O-β-glucopyranoside O-(6''-malonyl) glucoside R1 H 3-O- β-rutinoside 3-O-β-D-glucoside R1 O-β-D-glucoside R2 H H H H H H O-α-rhamnopyranoside O-β-D-glucoside H R2 H H O-β-glucopyranoside H H Compound no. 12 13 14 Compound no. 16 Compound no. 1 2 3 4 5 6 7 98 99 Compound no. 8 9 10 11 100 R1 H O-β-D-glucopyranoside R1 O-[β-D-2-O sulphonyl quinovopyranosyl O-β-Dquinovopyranosyl http://aprh.journals.ekb.eg/ 8 Compound no. 18 19 R2 O-β-Dglucopyranosyl O-β-Dglucopyranosyl Compound no. 35 70 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) R1 O- α-L-arabinoside O- β -D-glucopyranosyl O- β- D- glucopyranosyl Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 R2 H β -D-2-O-sulfonyl-galactopyranoside O-α-L-arabinoside R1 α-L-arabinopyranosyl-(1→2)-β-D-glucopyranosyl β- D- glucose β-D-(2-O-sulphonyl)- quinovo pyranosyl α-L-rhamnoside O-β-D-glucopyranosyl O-β-D-quinovo pyranosyl O-α-L-arabinopyranosyl-(1→2)-β-D-quinovopyranosyl O-α-L-arabinopyranosyl-(1→2)-β-D-quinovo pyranosyl O-α-L-arabinopyranosyl-(1→2)-β-D-glucopyranosyl O-β-D-2-O-sulphonyl glucopyranosyl O-β-D-2–O-sulphonyl glucopyranosyl O- β-D-2–O-sulphonyl quinovo pyranosyl O- β –D 2-O-sulfo- xylopyranosyl O- β –D 2-O-sulfo- xylopyranosyl O- β{[6-deoxy-α-L-mannopyranosyl-(1→2)-α-Larabinopyranosyl-(1→2)-β-D-glucopyranurosonyl] 2-O-sulfo-β-D-glucopyranurosonyl O-β-D-xylopyranosyl (1→2) quinovo pyranosyl O-β-D-quinovo pyranosyl R1 O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl(1→2)-β -D-glucopyranosyl O- α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl(1→2)- β -D-glucopyranosyl Compound no. 28 29 30 R2 H H H H O-β-D-glucopyranosyl O-β-D glucose H O-β-D glucose O-β-D glucose H O-β-D glucose O-β-D glucose H O-β-D glucose 2-O-sulfo-β-D-glucopyranosyl Compound no. 31 32 33 34 36 38 39 40 41 42 43 44 48 49 50 2-O-sulfo-β-D-glucopyranosyl O-β-D glucose H 51 52 69 R2 O- β-D (2-O-sulphonyl) glucopyranosyl Compound no. 45 O-β- D glucose 46 http://aprh.journals.ekb.eg/ 9 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) R1 H O-β- D glucose R2 CHO CH2OH Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 R1 H α-hydroperoxy Compound no. 53 54 R1 β – O- α- L rhamnopyranosyl (1→2) - α- L- arabinopyranosyl – (1→2) – β – D- glucopyranosyl β – O- α- L rhamnopyranosyl (1→2) - α- L- arabinopyranosyl – (1→2) – β – D- glucopyranosyl Compound no. 74 75 R2 O- β – D-glucopyranosyl Compound no. 96 O- β – D-2-Osulphonylglucopyranosyl 97 15 17 20 21 22 23 24 25 http://aprh.journals.ekb.eg/ 10 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) 26 Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 27 37 47 R1: β-D- 4’’’-O- acetyl glucosyl (1’’’-2’’) –β- D – glucose 55 56 57 58 59 60 61 62 63 64 65 66 http://aprh.journals.ekb.eg/ 11 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 67 68 71 72 73 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 http://aprh.journals.ekb.eg/ 12 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 91 92 95 R1 H OCH3 93 94 103 104 Cpd no. 101 102 105 Figure 1. Structures of isolated compounds from different Zygophyllum species Hypoglycemic and hypolipidemic activities of the aqueous extract of Z. gaetulum showed hypoglycemic and hypolipidemic activities in Streptozotocin induced-diabetic rats11,61, these effects may be due to the antioxidant potential of this plant. Moreover, Z. gaetulum aqueous extract prevented lipid peroxidation by enhancing PON1 {paraoxinase activity} and LCAT {Lecithin cholesterol acyltransferase} activities. In addition, it reduced oxidative stress in the liver and kidney by decreasing thiobarbituric acid reactive substances levels and increasing antioxidant enzyme activities11. Oral administration of Z. simplex to hyperlipidemic rats were appreciably effective in decreasing the levels of serum total cholesterol, low-density lipoprotein cholesterol, triacylglycerol and tissue lipid accumulation while increasing the levels of serum high-density lipoprotein cholesterol, adjusting the metabolic disturbance of lipoprotein and increasing the antioxidant enzyme activity and repressing the development of atherosclerosis 66. CONCLUSION In the review, chemical investigations and biological activity have been reported for only 16 out of 100 known Zygophyllum species. However, members of Zygophyllum, such as Z. album and Z. simplex, revealed significant biological activity, especially as anti-inflammatory and antioxidant. Investigation of the chemical constituents of plants of genus Zygophyllum showed diverse compounds, including triterpenes, http://aprh.journals.ekb.eg/ 13 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 saponins, flavonoids, sterols and simple phenolic compounds. It should be emphasized that phenolic compounds from Z. cornutum, Z. album, Z. cocceniem, Z. hamiense, Z. simplex and Z. fabago had particularly prominent anti-oxidant activity, in addition to some other biological properties. Also, the presence of essential oils and saponins in Z. cornutum contributed to its antidiabetic activity. Previous studies have provided a base for the medicinal use of Zygophyllum species. It is important to note that the safety and toxicity of Zygophyllum species have not been explored. Therefore, the toxicities of traditional remedies and isolated chemical compounds should be further assessed as well. 9. 10. 11. Conflict of Interest The authors declare that they don’t have any kind of conflict of interest. 12. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. Hammoda, H.M.; Ghazy, N.M.; Harraz, F.M.; Radwan, M.M.; El Sohly, M.A.; Abdallah, I.I. Chemical constituents from Tribulus terrestris and screening of their antioxidant activity. Phytochemistry 2013, 92, 153-159. Nabiel, A.M.; Saleh, M. N. An approach to the chemosystematics of the Zygophyllaceae. Biochem. Syst. Ecol. 1977, 5 (2), 121-128. Hammad, I.; Qari, S.H. Genetic diversity among Zygophyllum (Zygophyllaceae) populations based on RAPD analysis. Genet. Mol. Res. 2010, 9(4), 2412-2420. Fatemeh, A. C.; Mohsen, E.; Mostafa, F.A.; Zarrin, T. B. Karyotype analysis and new chromosome number reports in Zygophyllum species. Caryologia. 2014, 67 (4), 321-324. Sheahan, D. F.; Cutler, F. L. S. Contribution of vegetative anatomy to the systematics of the Zygophyllaceae. Bot. J. Linean. Soc. 1993, 113 (3), 227-262. Soumaya, B.; Wided, M.; Riadh, K. The Halophytic Genus Zygophyllum and Nitraria from North Africa: A Phytochemical and Pharmacological Overview In. Medicinal and Aromatic Plants of the World - Africa, 1st Edn.; Neffati, M.; Najjaa, H.; Máthé, Á.; Springer, Netherlands. 2017, (3), pp. 345-356. El-Shora, H. M.; El-Amier, Y. A.; Awad, M. H. Antioxidant Activity of Leaf Extracts from Zygophyllum coccineum L. collected from Desert and Coastal Habitats of Egypt. Int. J. Curr. Micro. App. Sci. 2016, 5 (4), 635-641. Mouna, K.; Hichem, B. S.; Rania, M.; Noureddine, A. Anti-oxidant and anti-acetylcholinesterase 13. 14. 15. 16. 17. 18. 19. 20. activities of Zygophyllum album. Bangladesh J. Pharmacol. 2015, 11 (1), 54-62. Gibbons, S.; Oriowo, M. A. Antihypertensive effect of an aqueous extract of Zygophyllum coccineum L. in rats. Phytother. Res. 2001, 15 (5), 452-455. Mahdi, B.; Hocine, D.; Zaouia, K.; Belfar, A.; Bensaci, C.; Mohamed, H. Antioxidant activities, phenolic, flavonoid and tannin contents of endemic Zygophyllum Cornutum Coss. From Algerian Sahara. Der Pharma Chemica. 2015, 7 (11), 312 – 317. Akila, G.; Djamil, K.; Samira, Z.; Sadia, B. Zygophyllum gaetulum aqueous extract protects against diabetic dyslipidemia and attenuates liver and kidney oxidative damage in streptozotocin induced-diabetic rats. Int. J. Pharm. Sci. Res. 2014, 5 (11), 4709 - 4717. Houria, M.; Tabti, B. Antidiabetic effect of the aerial part ethanolic extracts of Zygophyllum geslini Coss. in streptozotocin induced-diabetic rats. Metabol. Func. Res. 2012, 5, 17-20. Ebrahim, T.; Rasoul, B. Z. N.; Saied, K. Green synthesis of silver nanoparticles using Zygophyllum Qatarense Hadidi leaf extract and evaluation of their antifungal activities. JAPS. 2018, 8 (3), 168171. Mnafgui, K.; Kchaou, M.; Ben Salah, H.; Hajji, R.; Khabbabi, G.; Elfeki, A.; Allouche, N.; Gharsallah, N. Essential oil of Zygophyllum album inhibits key-digestive enzymes related to diabetes and hypertension and attenuates symptoms of diarrhea in alloxan-induced diabetic rats. J. of Pharm. Biol. 2016, 54 (8), 1326-1333. El Badry, M.A.; El Aasser, M. M.; El Shiekh, H. H.; Sheriff, M. M. Evaluation of Antimicrobial, Cytotoxic and Larvicidal Activity of Zygophyllum Coccineum North Sinai, Egypt. J. Med. Aromat. Plants. 2015, 4 (214), 2167-0412.100021. Varsha, S.; Kishan, G. R. Salt stress enhanced antioxidant response in callus of three halophytes (Salsola baryosma, Trianthema triquetra, Zygophyllum simplex) of Thar Desert. Biologia. 2014, 69 (2), 178-185. Emad, M. A.; Gamal, E. G. Screening for antimicrobial activity of some plants from Saudi folk medicine. GJRMI. 2013, 2 (4), 210-218. Ahmed, A. Z.; Zulfiqar, A. l.; Yasser, A. E.; Ikhlas, A. K. A new lignan from Zygophyllum aegyptium. Magn. Reson. Chem. 2016, 54 (9), 771-773. Jiangbo, H.; Xiaoman, L.; Yanfen, N.; Jian, T.; Bo, W.; Jing, J.; Weiwei, C. Four new compounds from Zygophyllum fabago L. Phytochem. Lett. 2016, 15, 116-120. Ganbaatar, C.; Gruner, M.; Tunsag, J.; Batsuren, D.; Ganpurev, B.; Chuluunnyam, L.; Sodbayar, http://aprh.journals.ekb.eg/ 14 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 B.; Schmidt, A. W.; Knölker, H. J. Chemical constituents isolated from Zygophyllum melongena Bunge growing in Mongolia. Nat. Prod. Res. 2016, 30 (14), 1661-1664. Abdel-Hamid, R. A.; Ross, S. A. ; Abilov, Z. A.; Sultanova, N. A. Flavonoids and Sterols from Zygophyllum fabago. Chem. Nat. Compd. 2016, 52 (2), 318-319. Hashim, A. H.; Ezz, K. D. An acylated isorhamnetin glucoside from Zygophyllum simplex. Phytochemistry. 1992, 31(9), 3293-3294. Hani, M.; Kamel, A. E.; Shaker, H.; Pöllmann, K.; Seifert, K. Triterpenoid saponins from Zygophyllum species. Phytochemistry 1995, 40 (4), 1233-1236. Ahmed, A. Z.; Yasser, A. E. A.; Zulfiqar, A.; Iftikhar, A. K. Triterpinoidal saponins from Zygophyllum aegyptium. Planta Medica. 2015, 81 (5). Ahmad, V. U.; Iqbal, S.; Nawaz, S. A.; Choudhary, M. I.; Farooq, U.; Ali, S. T.; Ahmad, A.; Bader, S.; Kousar, F.; Arshad, S.; Tareen, R. B. Isolation of four new pterocarpans from Zygophyllum eurypterum (syn. Z. atriplicoides) with enzyme‐inhibition properties. Chem. Biodiverse. 2006, 3 (9), 996-1003. Yasser, A. E.; Hamed, E.S.; Hesham, M. Ecological Study on Zygophyllum coccineum L. in Coastal and Inland Desert of Egypt. Agric. Ecol. Res. Inter. 2016, 6 (4), 1-17. Karl, P.; Katja, S.; Ulrich, S.; Hani, M.; Ahmed, E.; Kamel, H. S.; Karlheinz, S. Triterpenoid saponins from Zygophyllum decumbens. Phytochemistry 1998, 48 (5), 875-880. Shehab, N.G.; Abu-Gharbieh, E.; Bayoumi, F.A. Impact of phenolic composition on hepatoprotective and antioxidant effects of four desert medicinal plants. BMC complement. Altern. Med. 2015, 15 (1), 401. Kaplan, D.; Maymon, M.; Agapakis, C. M.; Lee, A.; Wang, A.; Prigge, B. A.; Volkogon, M.; Hirsch, A. M. A survey of the microbial community in the rhizosphere of two dominant shrubs of the Negev Desert highlands, Zygophyllum dumosum (Zygophyllaceae) and Atriplex halimus (Amaranthaceae), using cultivation-dependent and cultivation-independent methods. Am. J. Bot. 2013, 100 (9), 1713 – 1725. Dhafer, A. A. Z.; Enas, J. A. B. Systematic studies on the Zygophyllaceae of Saudi Arabia: new combinations in Tetraena Maxim. Turk. J. Bot. 2017, 41, 96-106. Xiao-rong, Y.; Xiang-feng, Z.; Xue-mei, Z.; Hongyan, G. Analgesic and Anti-inflammatory Activities and mechanisms of 70% ethanol extract 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. of Zygophyllum macropodum in Animals. CHM. 2017, 10 (1), 59-65. Daradka, H.M. Evaluation of Hematological and Biochemical Activity of Ethanolic Extract of Zygophyllum simplex Linn. in Wistar Rats. PJBS. 2016, 19 (4), 179 - 184. Ksouri, W.M.; Medini, F.; Mkadmini, K.; Legault, J.; Magné, C.; Abdelly, C.; Ksouri, R. LC–ESITOF–MS identification of bioactive secondary metabolites involved in the antioxidant, antiinflammatory and anticancer activities of the edible halophyte Zygophyllum album Desf. Food Chem. 2013, 139 (1), 1073-1080. Belmimoun, A.; Meddah, B.; Side, L. K.; Sonnet, P.Phytochemical study of Zygophyllum album extract. JET-M 2017, 4 (5), 1-10. Kchaou, M.; Ben Salah, H.; Kais, M.; Noureddine, A. Chemical Composition and Biological Activities of Zygophyllum album (L.) Essential Oil from Tunisia. JAST. 2016, 18 (6): p. 1499-1510. Rezuanul I.; Yong T. J.; Yong S. L.; Chi H. S. Isolation of antifungal compounds from some Zygophyllum species and their bioassay against two soil-borne plant pathogens. Folia Microbial. 1994, 39 (3), 215-221. Kais, M.; Khaled, H.; Hichem, B. S.; Mouna, K.; Mbarek, N.; Sadok, S.; Fatma, D.; Noureddine, A.; Abdelfattah, E. Inhibitory Activities of Zygophyllum album: A Natural WeightLowering Plant on Key Enzymes in High-Fat DietFed Rats . Evid. Based Complement. Alternat. Med. 2012, 10, 384 – 392. Amal, M.Y.; Mostafa, A. I. K.; Faiza, M. H.; Husseiny, A. H. Phytochemical and toxicological studies on Zygophyllum album L.F. J. Pharmacol. Toxicol. 2007, 2 (3), 220-237. Tigrine, K. N.; Meklati, B.Y.; Chemat, F. Contribution of microwave accelerated distillation in the extraction of the essential oil of Zygophyllum album L. Phytochem. Anal. 2011, 22 (1), 1-9. Ahmad, V.U.; Iqbal, S.; Kousar, F.; Bader, S.; Arshad, S.; Tareen, R. B. Two new saponins from Zygophyllum atriplicoides. Chem. Pharm. Bull. 2005, 53 (9), 1126-1130. Mamdouh, A.M.; Layth, M. S.; Menna Allah, H. A Comparative Study on Phytochemical Constituents of Zygophyllum coccineum L. in Coastal and Inland desert of Egypt. IJSE 2015, 4 (5), 353.355. Elham, A.; Seham, S. E. H.; Mohamed, M. F.; Imtaz, A. K. Zygophylloside S, a New Triterpenoid Saponin from the Aerial Parts of Zygophyllum coccineum L. Planta Medica. 2010, 76 (5), 51. Ayad, M. R.; Azouzi, S.; Louaar, S.; Akkal, H. D.; Medjroubi, K. Phytochemical investigation of the endemic plant Zygophyllum cornutum. Chem. Nat. Prod. 2012, 48 (2), 313-314. http://aprh.journals.ekb.eg/ 15 ISSN: 2357-0547 (Print) ISSN: 2357-0539 (Online) Review Article / JAPR Shawky et al., 2019, 3 (1), 1-16 44. Sobirdjan, A. S.; Putieva, Z. M. ; Kachala, V. V. ; Saatov, Z. ; Shashkov, A. S. Triterpene glycosides of Zygophyllum eichwaldii. Ii. Structure of zygoeichwaloside I. Chem. Nat. Prod. 2001, 37 (4), 347-350. 45. Saleha, S. K.; Afsar, K.; Amir, A.; Viqar, U. A.; Umar, F.; Saima, A.; Sadia, B.; Aqib, Z.; Imran, N. S.; Bilge, S.; Nurgun, E. Two new disulfated triterpenoids from Zygophyllum fabago. Helv. Chim. Acta. 2010, 93 (10), 2070-2074. 46. Yaripour, S.; Delnavazi, M. R.; Asgharian, P.; Valiyari, S.; Tavakoli, S.; Nazemiyeh, H. A survey on phytochemical composition and biological activity of Zygophyllum fabago from Iran. APB. 2017, 7 (1), 109 - 114. 47. Hossein, M.; Mohmmad, V.; Reza, S. Chemical composition of essential oil of Zygophyllum fabago L. from North-West Iran. Int. J. Herb. Med. 2015, 2 (6), 34-37. 48. He, J.H.; Niu, Y. F.; Li, J. X.; Wang, L. B.; Zi, T. P.; Yu, S.; Tao, J. Studies on terpenoids from Zygophyllum fabago. Zhongguo Zhong Yao Za Zhi. 2015, 40 (23), 4634-4638 49. Khayari, M. E. A.; Benharref, A.; Abbad, A.; Bekkouche, K.; Larhsini, M.; Jamali, C. A.; Markouk, M.; Taourirte, M. Chemical Composition of Essential Oils and Mineral Contents of Zygophyllum gaetulum (Emb. and Maire). J. Essent. Oil Bear. Pl. 2017, 20 (6), 16451650. 50. Omar, S.; Souad, F. T.; Nunziatina, D. T.; Rita, A. Saponins from Zygophyllum gaetulum. Nat. Prod. 1998, 61 (1), 130 – 134. 51. Dalila, S.; Anne, C.; Mitaine, O.; Tomofumi, M. V. H.; Marie, A.; Lacaille, D. Ursane‐Type Triterpene Saponins from Zygophyllum geslini. Helv. Chim. Acta. 2007, 90 (4), 712-719. 52. Viqar, U. A.; Ghazala, S. U.; Mohammad, S. A. Saponins from Zygophyllum propinquum. Phytochemistry. 1993, 33 (2), 453-455. 53. Sameh, H.; Mona, M.; Lamyaa, F. I.; Nabiel, A.M.S. Flavonoids of Zygophyllum album Lf and Zygophyllum simplex L.(Zygophyllaceae). Biochem. System. Ecol. 2011, 39 (4-6), 778-780. 54. Elham, A.; Seham, S. E. H.; Mohamed, M. F.; Rabab, M.; Khan, I. A. A Phytochemical Study of Zygophyllum simplex L. Planta Medica. 2011, 77, 40 55. Mnafgui, K; Kchaou, M.; Hamden, K.; Derbali, F.; Slama, S.; Nasri, M.; Salah, H. B.; Allouche, N.; Elfeki, A. Inhibition of carbohydrate and lipid digestive enzymes activities by Zygophyllum album extracts: effect on blood and pancreas inflammatory biomarkers in alloxan-induced diabetic rats. Physiol. Biochem. 2014, 70 (1), 93106. 56. Ghoul, J. E.; Boughattas, N. A.; Ben Attia, M. Antihyperglycemic and antihyperlipidemic activities of ethanolic extract of Zygophyllum album in streptozotocin-induced diabetic mice. Toxicol. Ind. Health. 2013, 29 (1), 43-51. 57. Ishrak, K. K.; Ahmed, D. The efficiency of random versus ethno-directed research in the evaluation of Sinai medicinal plants for bioactive compounds. J. Ethnopharmacol. 2000, 71 (3), 365-376. 58. Awatif, B.; Samira, F.; Houda, S.; Fatima, K. T.; Cherifa, B. Therapeutic Effect of Zygophyllum cornutum on Metabolic Disturbances, Oxidative Stress in Heart Tissue and Histological Changes in Myocardium of Streptozotocin-induced Diabetic Rats. Life Sci. 2016, 10, 192-197. 59. AL-Qaissi, E. Antimicrobial activity of petroleum ether extracts from leaves, seeds and roots of Zygophyllum fabago L. towards some microorganisms. Ibn AL-Haitham Journal for Pure and Applied Science. 2017, 21 (2), 1-14. 60. Saleha, S. K.; Ajmal, K.; Afsar, K.; Abdul, W.; Umar, F.; Amir, A.; Aqib, Z.; Viqar, U. A.; Bilge, S.; Nurgun, E. Urease inhibitory activity of ursane type sulfated saponins from the aerial parts of Zygophyllum fabago Linn. Phytomedicine. 2014, 21 (3), 379-382. 61. Jaouhari, J. T.; Lazrek, H. B.; Jana, M. The hypoglycemic activity of Zygophyllum gaetulum extracts in alloxan-induced hyperglycemic rats. J. Ethnopharmacol. 2000, 69 (1), 17-20. 62. Anna, C.; Safir, O.S; Fkih, T.; Ludovico, S.; Rita, A. Properties and effects on isolated guinea-pig ileum of Zygophyllum gaetulum species endemic in Moroccan Sahara. Pharm. Biol. 1998, 36 (5), 320326. 63. Kouadri, B. W.; Hammadi, K. Evaluation of Antidiabetic Activity of Two Plants Berberis vulgaris and Zygophyllum geslini. J. Phys. Chem. Biophys. 2017, 7 (1), 236 -240. 64. Abdallah, H.M.; Esmat, A. Antioxidant and antiinflammatory activities of the major phenolics from Zygophyllum simplex L. J. Ethnopharmacol. 2017, 205, 51-56. 65. Kumar, H.; Kakrani, N.; Kakrani, P.; Kumar, A. S. Evaluation of analgesic and anti-inflammatory activity of Ethyl acetate extract of Zygophyllum simplex Linn. herb. Int. J. Res. Phytochem. Pharmacol. 2011, 1, 180-183. 66. Haytham, M. D.; Kamal, M. S. M.; Bandar, R. A. S.;, Abdul Mannan, M.; Yaser, S. B. N.; Muwaffa, G. B.; Jalal, A. J. Antihyperlipidemic activity of Zygophyullum Simplex ethanolic extract on high cholestrol diet induced hyperlipidemia in rats. IJBPAS. 2017, 6 (12), 2414-2430. http://aprh.journals.ekb.eg/ 16