IJRPC 2013, 3(1) Borhade Pravin et al ISSN: 22312781

INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY

Available online at www.ijrpc.com Review Article

REVIEW ON colocynthis Borhade Pravin1*, Deshmukh Tushar1, Patil Vijay1 and Khandelwal Kishanchnad2, 1Department of Pharmacognosy, TVES’s Hon. Loksevak Madukarrao Chaudhari College of Pharmacy, Faizpur, Jalgaon, Maharashtra, . 2Department of Pharmacognosy, JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune, , TVES’s Hon. Loksevak Madukarrao Chaudhari College of Pharmacy, Faizpur, Jalgaon, Maharashtra, India.

ABSTRACT Citrullus colocynthis [Family: ]. This is perennial usually trailing. Commonly found wild in the sandy lands of North West, the Punjab, Sind, and Central and southern India, and coromandal coast. Also found indigenous in Arabia, West , and Tropical Africa and in the Mediterranean region. Commonly Citrullus colocynthis known as - Indravaruni (Sanskrit),

Chitrapala or Bitter apple. Medicinally , bark and are used. Citrullus colocynthis shows mild stomachic, bitter tonic, diuretic and antilithic property. As per Ayurveda and Siddha system of medicine it is Tikta-rasam, ushna-veeryam and katu vipakam and used as purgative, diuretic, lagu, kapharam and abortifacient. is bitter, pungent and used as purgative, anthelmintic, antipyretic, carminative, cures tumors, leucoderma, ulcers, asthma, etc. Root is useful in jaundice, ascites, urinary disease, rheumatism.

Keywords: Citrullus colocynthis, Cucurbitaceae, Indravaruni, Bitter apple.

INTRODUCTION BOTANICAL DESCRIPTION Citrullus colocynthis [Family: Cucurbitaceae]. This is perennial herbs usually trailing. The angular leaves are alternately located on Commonly found wild in the sandy lands of long petioles. Each leaf is almost 5 to 10 North West, the Punjab, Sind, and Central and centimeters in length and has around 3 to 7 southern India, and coromandal coast. Also lobes. Sometimes the middle lobe might have found indigenous in Arabia, West Asia, and an ovate structure. The leaves have a Tropical Africa and in the Mediterranean triangular shape with many clefts. The leaves region. It originally bore the scientific name have a rough, hairy texture with open sinuses. Colocynthis citrullus, but is now classified as The upper surface of the leaves are fine green Citrullus colocynthis. Tendrils are simple, 2- in color and the lower surface is comparatively 3fits slender and hairy. Leaves are very pale. variable in size. Wild leaf is 3.8 to 6.3 cm in length and 2.5 cm in width while cultivated are Fruit large in size. Leaf show deltoid margin, pale Each bitter apple produces around 15 to green colour above and ashy colour beneath, 30 globular having a diameter of almost scabrid on both surface, 5-7 lobed. Citrullus 7 to 10 centimeters. The outer portion of the colocynthis shows presence of male and fruit is covered with a green skin having yellow female . Fruit are globular, slightly stripes. The fruits may also be yellow in color. depressed, 5 – 7.5 cm in diameter, green in The ripe fruits are characterized by a thin but colour and get white glabrous when ripe. Fruit hard rind. The fruits have a soft, white pulp filled with a dry spongy very bitter pulp. which is filled with numerous ovate are 4 – 6 mm long and pale brown. compressed seeds.

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Flowers dyspepsia, constipation, anemia, throat The yellow-colored flowers appear singly at diseases, elephantiasis, joints pain. leaf axils. They are monoecious; the pistils and 2. Root is useful in jaundice, ascites, urinary are present in different flowers of the diseases, rheumatism and given in same plant. They have long peduncles. Each abdominal enlargements and in cough and is also comprised of a yellow asthmatic attacks of children. A poultice of campanulate. The corolla has five lobes and root useful in inflammation of the breast. the calyx is parted five ways. The female 3. Fruit or root with or without nux-vomica is flowers are easily identified from the males by rubbed into a paste with water and applied their villous, hairy ovary. to boils and pimples. 4. Past of the root is applied to the enlargement of abdomen of children1, 2. The seeds are around 6 mm in size, smooth, compressed and ovoid-shaped. They are located on the parietal placenta. The seeds PHYTOCHEMICAL CONSTITUENTS3,4,5 are light yellowish-orange to dark brown in The main chemical contain of fruit pulp color. colocynthin (the bitter principle upto 14 %), colocynthein (resin), colocynthetin, pectin Root gum. Seed contain a fixed oil (17 %) and The Bitter Apple plant has a large perennial albuminiods (6 %). Investigated chemical root that sends out long and slender, angular, content is mentioned in Table 1. tough, rough -like stems. The stems are normally spread on the ground and have a PHARMACOLOGICAL ACTIVITY tendency to climb over herbs and by 1. Anti-inflammatory their axillary branching tendrils. Belsem Marzouk and et al study aqueous extracts C. colocynthis fruit and seed at Distribution immature state for anti-inflammatory activity Citrullus colocynthis found throughout India using the carrageenan induced paw edema and Ceylon, both wild and cultivated. It is also assay in rats. The best anti-inflammatory indigenous in the Arabia, west Asia, tropical activities were obtained with immature fruits Africa, Mediterranean region. from south Tunisia. Therefore, C. colocynthis Schrad. Could be a potential Vernacular names in India useful product suitable for further Sanskrit → Indravaruni evaluation for inflammatory diseases6. Hindi → Indrayan English → Colocynth 2. Anticandidal and antibacterial Bengali → Makhal Rasool Khatibi and et al assess in vitro Gujarati → Indrayan antibacterial and Anticandidal activity of Marathi → Kadu –indravani aqueous and diluted acetone extracts of C. Telugu → Eti-puchcha colocynthis Schrad. MIC and MBC/MFC Tamil → Paedikari Attutummatti were determined for plant organs at Malyalam → Paikummatti different maturation stages. Aqueous and Punjabi → Ghurunba diluted acetone extracts (from the plant’s , stems, leaves and three maturation AYURVEDA AND SIDDHA ACTION stages of its fruit and seeds) were screened As per Ayurveda and Siddha system of for activity against Gram-negative and medicine Citrullus colocynthis is Tikta –rasam, Gram-positive bacteria (Escherichia coli, ushna veeryam, katu vipakam, purgative, Pseudomonas aeruginosa, Staphylococcus diuretic, lagu, kaphaharam, puerperal aureus and Enterococcus faecalis) and disorders, abortifacient, ascites and dropsy. various Candida spp. (Candida glabrata, Oil from seed used in hair growth and maladu. Candida albicans, Candida parapsilosis and Candida kreusei). All extracts showed MEDICINAL VALUE OF CITRULLUS activity against all strains. The highest COLOCYNTHIS MICs and MBCs/MFCs were obtained from 1. The fruits are bitter, pungent, cooling, the fruit aqueous extracts (MIC 0.10 mg/ml purgative, anthelmintic, antipyretic, against C. albicans and C. glabrata, carminative, cures tumors, ascites, 0.20 mg/ml against E. coli and P. leucoderma, ulcers, asthma, bronchitis, aeruginosa), lowest activity from the root urinary discharges, jaundice, enlargement extracts. C. colocynthis Schrad shows of spleen, tuberculosis glands of the neck, antibacterial and Anticandidal properties. 7

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3. Antioxidant, anti-inflammatory/ results were obtained with immature fruits analgesic or anti-proliferative followed by seeds. The stem and root Saba AB and et al isolated Cucurbitacins extracts were shown to possess the less are triterpenoid steroids. It is efficient anti- significant inhibitory activity against oxidant and this property lies in their ability analgesic and anti-inflammatory models. to scavenge free-radicals such as hydroxyl Citrullus colocynthis Schrad. is a potentially radical, superoxide anions and singlet useful drug suitable for further evaluation oxygen. This broad spectrum radical- for rheumatoid arthritis and its folk scavenging capacity surpasses what had medicinal use as an analgesic and anti- been reported for other natural antioxidants inflammatory agents is validated10,11. such as grape-seed extract, wheat, alfalfa and ginkgo biloba extracts. Reports also 6. Hypolipidemic show that cucurbitacins adequately inhibit Rahbar AR and et al investigate the lipid peroxidation and oxidation8. hypolipidemic effect of Citrullus colocynthis beyond the hypoglycemic impact on 4. Hypoglycemic human. One hundred dislipidemic patients Agarwal V and et al examine the effect of were randomly divided into two groups root of C. colocynthis on the biochemical namely treated (n = 50) group and placebo parameters of normal and alloxan-induced (n = 50) group. The subjects were treated diabetic rats. Diabetes mellitus was induced daily by powdered seeds of Citrullus by intraperitoneal (120 mg/kg b.w.) injection colocynthis (300 mg) and placebo for 6 of alloxan monohydrate for three days and weeks. The serums, TG, Chol, LDL-C, the animals showing blood glucose level in HDL-C, SGOT and SGPT were measured the range of 175-300 mg/dL were selected with enzymatic methods at the beginning for study. The blood glucose concentrations and the end of the project. The significance of the animals were measured at the of differences within these groups was beginning of the study and the calculated by Paired T-test and by analysis measurements were repeated on 3rd, 5th of covariance between them. There were and 7th day after the start of the significant differences within and between experiment. On day 7, blood was collected treated and placebo groups during our by cardiac puncture under mild ether treatment in TG and in Cholesterol after anesthesia. Aqueous extract of roots of intervention (p < 0.05). A daily intake of 300 Citrullus colocynthis showed significant mg day(-1) of powdered seeds of Citrullus reduction in blood sugar level (58.70%) colocynthis can lower the triglyceride and when compared with chloroform (34.72%) cholesterol concentration significantly in and ethanol extracts (36.60%) (p < 0.01). nondiabetic hyperlipidemic patients12. The aqueous extracts showed improvement in parameters like body weight, serum 7. Anti – alopecia creatinine, serum urea and serum protein Dhanotia R and et al evaluated C. as well as lipid profile and also restored the colocynthis for hair growth activity in serum level of bilirubin total, conjugated androgen-induced alopecia. Petroleum bilirubin, serum glutamate oxaloacetate ether extract of C. colocynthis was applied transaminase (SGOT), serum glutamate topically for its hair growth-promoting pyruvate transminase (SGPT) and alkaline activity. Alopecia was induced in albino phosphatase (ALP)9. mice by testosterone administration intramuscularly for 21 days. Its inhibition by 5. Anti-inflammatory and analgesic simultaneous administration of extract was activities immature fruit and seed evaluated using follicular density, Marzouk B and et al screen the analgesic anagen/telogen (A/T) ratio and microscopic and anti-inflammatory activities of aqueous observation of skin sections. Finasteride extracts Citrullus colocynthis from roots and (5α-reductase inhibitor) solution was stems of the plant and from fruits and applied topically and served as positive seeds at different maturation stages. control. Petroleum ether extract of C. Method use for testing analgesic and anti- colocynthis exhibited promising hair growth- inflammatory activities using, respectively, promoting activity, as reflected from the acetic acid writhing test in mice and the follicular density, A/T ratio and skin carrageenan-induced paw edema assay in sections. The treatment was also rats. All extracts displayed analgesic and successful in bringing a greater number of anti-inflammatory activities at different hair follicles in anagenic phase than the doses without inducing acute toxicity. Topic standard finasteride. The result of treatment

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with 2 and 5% petroleum ether extracts 10. Antioxidant and free radical scavenging were comparable to the positive control Kumar S and et al study methanolic fruit finasteride. The petroleum ether extract of extract of C. colocynthis was screened to C. colocynthis and its isolate is useful in the evaluate its free radical scavenging effect. treatment of androgen-induced alopecia13. The highest antioxidant and free radical scavenging ability of the fruit extract was 8. Antibacterial and Anticandidal observed at a concentration of 2500 Marzouk B and et al assess in vitro microg mL(-1).16 antibacterial and Anticandidal activity of aqueous and diluted acetone extracts of 11. Larvicidal Citrullus colocynthis Schrad. MIC and Rahuman AA and et al tested larvicidal MBC/MFC were determined for plant activity of crude hexane, ethyl acetate, organs at different maturation stages. petroleum ether, acetone, and methanol Aqueous and diluted acetone extracts (from extracts of the leaf of five species of the plant's roots, stems, leaves and three cucurbitaceous against the early maturation stages of its fruit and seeds) fourth instar larvae of Aedes aegypti L. were screened for activity against Gram- and Culex quinquefasciatus (Say) negative and Gram-positive bacteria (Diptera: Culicidae). The larval mortality (Escherichia coli, Pseudomonas was observed after 24 h of exposure. All aeruginosa, Staphylococcus aureus and extracts showed moderate larvicidal Enterococcus faecalis)-and various effects; however, the highest larval Candida spp. (Candida glabrata, Candida mortality was found in petroleum ether albicans, Candida parapsilosis and extract of C. colocynthis, methanol Candida kreusei). RESULTS: All extracts extracts of C. indica, C. sativus, M. showed activity against all strains. The charantia, and acetone extract of T. highest MICs and MBCs/MFCs were anguina against the larvae of A. aegypti obtained from the fruit aqueous extracts (LC50=74.57, 309.46, 492.73, 199.14, and (MIC 0.10mg/ml against Candida albicans 554.20 ppm) and against C. and Candida glabrata, 0.20mg/ml against quinquefasciatus (LC50=88.24, 377.69, Escherichia coli and Pseudomonas 623.80, 207.61, and 842.34 ppm), aeruginosa), lowest activity from the root respectively. The petroleum ether extract extracts14. of C. colocynthis and methanol extract of M. charantia were more effective than the 9. larvicidal activity other extracts. 17 Rahuman AA and et al assayed Citrullus colocynthis (Linn.) Schrad, for their toxicity 12. Hypolipidaemic against the early fourth instar larvae of Daradka H and et al study the effect of Culex quinquefasciatus (Diptera: Citrullus colocynthis (70% EtOH) extract Culicidae). The larval mortality was on lipid profile on Rabbits. The plant observed after 24 h exposure. All extracts extract was orally administered to the showed moderate larvicidal effects; atherogenic rabbits (atherogenic diet + however, the highest larval mortality was cholesterol powder supplement 400 found in whole plant petroleum ether mg/kg/body weight/day dissolved in 5 mL extract of C. colocynthis. In the present coconut oil) at dose of 1.2 g kg(-1) body study, bioassay-guided fractionation of weight/day. During the hall period of the petroleum ether extract led to the experiment blood was collected and serum separation and identification of fatty acids; was analyzed for lipid profile. Animals and were isolated were sacrificed; the heart and the liver and identified as mosquito larvicidal were collected and kept at -20 degrees C compounds. Oleic and Linoleic acids were until assayed. Biochemical analysis of quite potent against fourth instar larvae of blood serum and tissue (liver and heart Aedes aegypti L. (LC50 8.80, 18.20 and muscle) level were made for cholesterol, LC90 35.39, 96.33 ppm), Anopheles Phospholipids and triglycerides. In addition stephensi Liston (LC50 9.79, 11.49 and blood serum was analyzed further for LC90 37.42, 47.35 ppm), and Culex HDL-Cholesterol. All the results were quinquefasciatus Say (LC50 7.66, 27.24 statistically analyzed using students t-test. and LC90 30.71, 70.38 ppm). The structure Hypolipidaemic nature of Citrullus was elucidated from infrared, ultraviolet, colocynthis (70% EtOH) extract was 1H-nuclear magnetic resonance, 13C- studied in hyperlipidaemic Rabbits. The NMR, and mass spectral data15. increased cholesterol levels were brought

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to normal by administration of Citrullus number. These results indicate that long- colocynthis. Serum cholesterol levels term exposure of female rats to Citrullus dropped from 940.7 to 230.41 (75.55%) colocynthis L. causes adverse effects on and further to 119.2 (87.32%) by the end the reproductive system and fertility19. of the experiment. Similarly, phospholipids and triglycerides levels were observed to 14. Type II diabetic clinical trial be also reduced. The tissues lipids profiles Huseini HF and et al conducted 2 month of liver and heart muscle showed similar clinical trial in 50 type II diabetic patients changes in those noticed in serum lipids. using powder of C. colocynthis. Two Citrullus colocynthis possesses active groups of 25 each under standard hypolipidaemic constituents.18 antidiabetic therapy, received 100 mg C. colocynthis fruit capsules or placebos 13. Effects on reproductive system and three times a day, respectively. The fertility patients were visited monthly and Qazan WSH and et al study toxic effects glycosylated hemoglobin (HbA1c), fasting of Citrullus colocynthis L. (400 mg/kg/body blood glucose, total cholesterol, LDL, HDL, wight) on the reproductive system after triglyceride, aspartate transaminase, administration to female Sprague-Dawley alanine transaminase, alkaline rats weighting 250-300 g for two time phosphatase, urea and creatinine levels periods 4 and 12 weeks. Twenty adult were determined at the beginning and female rats were divided into two groups after 2 months. The results showed a and Citrullus colocynthis L. were significant decrease in HbA1c and fasting intraperitoneally injected to experimental blood glucose levels in C. colocynthis animals in dose of 400 mg/kg/body wight. treated patients. Other serological First group containing 10 rats received parameters levels in both the groups did treatment for 4 weeks and a second group not change significantly. No notable of 10 rats received the same dose of gastrointestinal side effect was observed treatment for a period of 12 weeks and in either group. 20 compared with twenty non-exposed female rats received vehicle treatment. 15. Growth inhibitory activity on breast Female rats were allowed mating with cancer cells males after 10 days prior to the last Grossman S and et al study the effects of administration dose. Animals were cucurbitacin glucosides extracted from autopsied under light anesthesia after Citrullus colocynthis leaves on human mating and several parameters were breast cancer cell growth. Leaves were determined including: number of pregnant extracted, resulting in the identification of rats, body and reproductive organ weight, cucurbitacin B/E glucosides. The number of implantation sites, viable cucurbitacin glucoside combination (1:1) fetuses and resorption sites. Assessment inhibited growth of ER(+) MCF-7 and ER(- of pregnancies in females was measured ) MDA-MB-231 human breast cancer cell and the significance of these results was lines. Cell-cycle analysis showed that calculated using students t and Chi-square treatment with isolated cucurbitacin tests. The effect of Citrullus colocynthis L. glucoside combination resulted in exposure on fertility was assessed in accumulation of cells at the G(2)/M phase terms of pregnant rats number, of the cell cycle. Treated cells showed implantation sites, viable fetuses and rapid reduction in the level of the key resorption sites. Exposure to Citrullus protein complex necessary to the colocynthis L. for 4 weeks did not have regulation of G(2) exit and initiation of much effect on fertility. Significant mitosis, namely the p34(CDC2)/cyclin B1 decrease in the relative ovarian weights complex. cucurbitacin glucoside treatment and embryo weights in rats exposed to also caused changes in the overall cell Citrullus colocynthis L. were observed. morphology from an elongated form to a Exposure to Citrullus colocynthis L. for a round-shaped cell, which indicates that 12 weeks resulted in a reduction in the cucurbitacin treatment caused impairment percentage of pregnancies and in the of actin filament organization. This number of implantation sites when profound morphological change might also compared with controls in both treatment influence intracellular signaling by periods. Rats receiving 12 weeks molecules such as PKB, resulting in treatment showed a decrease in ovarian inhibition in the transmission of survival weights and a decrease in viable fetus's signals. Reduction in PKB phosphorylation

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and inhibition of survivin, an anti-apoptosis propionate (0.01 mg/rat/alternate day s.c.), family member, was observed. The and fruit extract along with testosterone treatment caused elevation in p-STAT3 propionate, respectively, for 30 days. and in p21(WAF), proven to be a STAT3 Significantly reduced cauda epididymis positive target in absence of survival sperm motility and density, number of signals. Cucurbitacin glucoside treatment pups, fertility, and circulatory levels of also induced apoptosis, as measured by testosterone were observed in all Annexin V/propidium iodide staining and treatment groups. The weights of testes, by changes in mitochondrial membrane epididymis, seminal vesicle, and prostate potential (DeltaPsi) using a fluorescent were significantly decreased in groups B, dye, JC-1. We suggest that cucurbitacin C, and D. The weights of all organs in the glucosides exhibit pleiotropic effects on different groups of the androgenicity study cells, causing both cell cycle arrest and were markedly decreased in group F when apoptosis. These results suggest that compared with group A, in group G when cucurbitacin glucosides might have compared with group F, and in group I therapeutic value against breast cancer when compared with group H, and cells.21 increased in group H when compared with group F. The serum testosterone levels 16. Antifertility also showed a similar pattern. The Chaturvedi M and et al screened 50% concentration of testicular cholesterol was ethanol extract of Citrullus Colocynthis significantly elevated, while protein, sialic Schrad in male albino rats for evaluation of acid, acid and alkaline phosphatase antifertility effects. The animals were concentrations were decreased. The divided into five groups: group A was a histoarchitecture of the testes showed vehicle-treated control group; treatment degenerative changes in the seminiferous groups B, C, and D received 100 epithelium, arrest of spermatogenesis at mg/kg/day C. Colocynthis extract for the secondary spermatocyte stage, periods of 20, 40, and 60 days, cytolysis, and the lumen filled with respectively, and group E animals eosinophilic material. Histometric received the extract at 100 mg/kg/day for parameters except Sertoli cell nuclear 60 days followed by 60 days of recovery. area and number of round spermatids For androgenicity evaluation of the extract, showed marked alterations. All altered the animals were divided into four groups: parameters restored to normal in group E. group F animals were castrated 30 days No changes were observed in body before the experiment to serve as controls, weight, litter size, hematology, and serum and group G, H, and I were subjected to biochemistry. In conclusion, a 50% ethanol castration 30 days before the experiments, extract of C. Colocynthis showed an followed by administration of fruit extract antiandrogenic nature, thereby reduced (100 mg/kg/day p.o.), testosterone reversible infertility in male albino rats.22

Table 1: Chemical content of Citrullus colocynthis S. No Part Chemical content (reported / Investigated ) 1. Fatty acid like Stearic, Myristic, Palmitic, oleic, Linoleic, Linolenic acid. 2. Protein 8.25 % and rich content rich in lysine, leucin and sulfo 1 Seed like methionine 3. Vitamin B1 , B2 and Niacin 4. Mineral like Ca, Mg, K, Mn, Fe, P and Zn Aerial part and Flavonoid glycoside quercetin, Flavone- 3- glucoside viz iso-vitexin, iso-orentine and iso- 2 fruit orentine -3-methyl ether. 1. Cucurbitane type triterpen glycoside viz colocynthoside A & B. 2. Cucurbitane type triterpen glycoside viz cucurbitacin E 2-O-beta-D-glcoside and its aglycone Cucurbitacin E. 3 Fruit 3. 2-O-beta-D-glucopyranosyl-16alpha-20R-dihyroxy-cucurbita-1,5,23E,25(26)- teraen-3,11,22-trione. 4. 2-O-beta-D-glcopyranosyl-cucurbitacin B and 2, 25-di-o-beta-D-glucopyranosyl- cucurbitacin L.

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REFERENCES 11. Marzouk B, Marzouk Z, Haloui E, 1. Kirtikar KR and Basu BD. Indian Fenina N, Bouraoui A and Aouni M. Medicinal Plants, International Book Screening of analgesic and anti- Distribution, Dehera Dun. 2006; 4th inflammatory activities of Citrullus Edn: 1147-1149. colocynthis from southern Tunisia. J 2. Nadkarni KM. Indian Materia Medica, Ethnopharmacol. 2010;128(1):15-19. Bombay Popular Prakashan, Bombay, 12. Rahbar AR and Nabipour I. The 2007;3rd Edn : 335-337. hypolipidemic effect of Citrullus 3. Gurudeeban S, Satyavani K and colocynthis on patients with Ramanathan T. Bitter Apple (Citrullus hyperlipidemia. Pak J Biol Sci. 2010; colocynthis): An overview of chemical 13(24):1202-1207. composition and biomedical 13. Dhanotia R, Chauhan NS, Saraf DK potentials. Asian J Plant Sci. 2010; 1: and Dixit VK. Effect of Citrullus 1-8. colocynthis Schrad fruits on 4. Yoshikawa M, Morikawa T, Kobayashi testosterone-induced alopecia. Nat H, Nakamura A, Matsuhira K, Prod Res. 2011; 25(15):1432-1443. Nakamura S and Matsuda H. 14. Marzouk B, Marzouk Z, Décor R, Bioactive saponins and glycoside. Edziri H, Haloui E, Fenina N and XXVII. Structure of new Cucurbitane – Aouni M. Antibacterial and type triterpen glycoside and Anticandidal screening of Tunisian antiallergic constituents from Citrullus Citrullus colocynthis Schrad. from colocynthis. Chem Pharm Bull Medenine. J Ethnopharmacol. 2009; (Tokyo). 2007; 55(3): 428-434. 125(2):344-349. 5. Nayab D, Ali D, Arshad N, Malik A, 15. Rahuman AA, Venkatesan P and Choudhary M and Ahmed Z. Gopalakrishnan G. Mosquito larvicidal Cucurbitacin glucoside from Citrullus activity of oleic and linoleic acids colocynthis. Nat Prod Res. isolated from Citrullus colocynthis 2006;20(5): 409-413. (Linn.) Schrad. Parasitol Res. 2008 6. Belsem M, Zohra M, Ehsen H, Manel ;103(6):1383-1390. T, Abderrahman B, Mahjoub A and 16. Kumar S, Kumar D, Saroha K, Singh Nadia F. Anti-inflammatory evaluation N and Vashishta B. Antioxidant and of immature fruit and seed aqueous free radical scavenging potential of extracts from several populations of Citrullus colocynthis (L.) Schrad. Tunisian Citrullus colocynthis Schrad. Methanolic fruit extract. Acta Pharm. African Journal of Biotechnology. 2008;58(2):215-220. 2011; 10(20):4217-4225. 17. Rahuman AA and Venkatesan P. 7. Rasool K and Jahanbakhsh T. Larvicidal efficacy of five Anticandidal screening and cucurbitaceous plant leaf extracts antibacterial of Citrullus colocynthis in against mosquito species. Parasitol South East of Iran. Journal of Res. 2008;103(1):133-139. Horticulture and Forestry. 2011;3(13): 18. Daradka H, Almasad MM, El-Banna 392–398. NM, Samara OH. Hypolipidaemic 8. Saba AB and Oridupa AO. Search for effects of Citrullus colocynthis L. in a novel antioxidant, anti-inflammatory/ rabbits. Pak J Biol Sci. 2007; analgesic or anti-proliferative drug: 10(16):2768-2771. Cucurbitacins hold the ace. Journal of 19. Qazan WSH, Almasad MM and Medicinal Plants Research. 2010; Daradka H. Short and long effects of 4(25): 2821-2826. Citrullus colocynthis L. on reproductive 9. Agarwal V, Sharma AK, Upadhyay A, system and fertility in female Spague- Singh G and Gupta R. Hypoglycemic Dawley rats. Pak J Biol Sci. effects of Citrullus colocynthis roots. 2007;10(16):2699-2703. Acta Pol Pharm. 2012;69(1):75-79. 20. Huseini HF, Darvishzadeh F, Heshmat 10. Marzouk B, Marzouk Z, Fenina N, R, Jafariazar Z, Raza M and Larijani Bouraoui A and Aouni M. Anti- B. The clinical investigation of Citrullus inflammatory and analgesic activities colocynthis (L.) schrad fruit in of Tunisian Citrullus colocynthis treatment of Type II diabetic patients: Schrad. Immature fruit and seed a randomized, double blind, placebo- organic extracts, Eur Rev Med controlled clinical trial. Phytother Res. Pharmacol Sci. 2011;15(6):665-672. 2009; 23(8):1186-1189.

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21. Grossman S, Dovrat S, Gottlieb HE 22. Chaturvedi M, Mali PC and Ansari AS. and Bergman M. Growth inhibitory Induction of reversible antifertility with activity of cucurbitacin glucosides a crude ethanol extracts of Citrullus isolated from Citrullus colocynthis on colocynthis Schrad fruit in male rats. human breast cancer cells. Tannin- Pharmacology. 2003; 68(1):38-48. Spitz T, Biochem Pharmacol. 2007; 73(1):56-67.

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