Influence of Citrullus colocynthis (L.) shrad. Extract on glucose level, lipid metabolism and oxidative homeostasis parameters of animals under experimental diabetes mellitus


  • H. R. Lamazyan Bogomolets National Medical University, Ukraine



C. colocynthis, type 2 diabetes, antioxidant activity, hypolipidemic action, C. colocynthis dry extract


Topicality. Diabetes mellitus is one of the most common chronic diseases. Among the methods of diabetes treating, phytotherapy occupies the remarkable place. Phytoproducts, as an alternative to synthetic drugs, are becoming increasingly popular due to the ability to exhibit multi-vector effects on the organism of the patient and to act in a complex manner.
The aim of the study was to investigate the hypoglycemic, hypolipidemic and antioxidant activity of Citrullus colocynthis dry extract, as a representative of medicinal plants with antidiabetic action.
Materials and methods. Hypoglycemic, hypolipidemic and antioxidant activity of C. colocynthis extract was investigated on Wistar rats with the model of type 2 diabetes mellitus. The plant extract was administered at doses of 50 mg/kg and 100 mg/kg, a reference drug “Arphazetyn” at a dose of 18 ml/kg for 28 days. The level of glucose was determined at the beginning and at the end of the experiment, the parameters of lipid (cholesterol, triglycerides, LDL, VLDL, HDL) and oxidative homeostasis (malonic dialdehyde, catalase, superoxidedismutase) – on the last day of the study.
Results and discussion. It has been established that C. colocynthis extract exhibits dose-dependent hypoglycemic and hypolipidemic effects. The most pronounced activity the plant extract exhibits at a dose of 100 mg/kg: lowers blood glucose levels as well as elevated parameters of lipid metabolism and increases the level of HDL. At a dose of 100 mg/kg it increases the activity of antioxidant enzymes, thereby reducing the level of malonic dialdehyde. The reference drug is inferior to the effectiveness of the C. colocynthis extract for all of these parameters.
Conclusions. According to results of the study, C. colocynthis extract has hypoglycemic, hypolipidemic and antioxidant effects.

Author Biography

H. R. Lamazyan, Bogomolets National Medical University

assistant of pharmacognosy and botany department


Tatiya, A. U., Kulkarni, A. S., Surana, S. J., Bari, N. D. (2010). Antioxidant and Hypolipidemic Effect of Caralluma adscendens Roxb. in Alloxanized

Diabetic Rats. International Journal of Pharmacology, 6 (4), 400–406. doi: 10.3923/ijp.2010.400.406

Anreddy, R. N. R., Porika, M., Yellu, N. R., Devarakond, R. K. (2010). Hypoglycemic and Hypolipidemic Activities of Trianthema portulacastrum

Linn. Plant in Normal and Alloxan Induced Diabetic Rats. International Journal of Pharmacology, 6 (2), 129–133. doi: 10.3923/ijp.2010.129.133

Ostovan, F., Olomi, H., Gol, A. (2014). The Citrullus Colocynthis pulp antioxidant activity on oxidative stress factors of liver in streptozotocin–induced

diabetic rats. Physiol. Pharmacol., 17 (4), 388–398.

Nishikawa, T., Edelstien, D., Du, X. L. (2000). Normalizing mitochondrial superoxide production blocks three pathways of hyperglglycemic damage.

Nature, 404, 787–790.

Chekina, N. A., Chukaiev, S. A., Nikolaiev, S. M. (2010). Sakharnyi diabet: vozmozhnosti pharmakoterapii s ispolzovaniiem sredstv rastitelnogo

proiskhozhdeniia. Vestn. Buriat. Universiteta, 12, 71–78.

Robertson, R. P. (2004). Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes. Journal of

Biological Chemistry, 279 (41), 42351–42354. doi: 10.1074/jbc.r400019200

Dallak, M., Bin–Jaliah, I. (2010). Antioxidant activity of Citrullus colocynthis pulp extract in the RBC’S of alloxan–induced diabetic rats. Pak. J.

Physiol., 6 (1), 1–5.

Limem, S., Banlipo, D., Karmous, T. (2016). Phytochemical composition and antioxidant power of Citrullus colcynthis from Togo. Int. J. Pharmacognosy

Phytochem. Res., 8 (3), 531–536.

Gurudeeban, S., Satyavani, K., Ramanathan, T. (2010). Bitter Apple (Citrullus colocynthis): An Overview of Chemical Composition and Biomedical

Potentials. Asian Journal of Plant Sciences, 9 (7), 394–401. doi: 10.3923/ajps.2010.394.401

Hussain, A. I., Rathore, H. A., Sattar, M. Z. A., Chatha, S. A. S., Ahmad, F. ud din, Ahmad, A., Johns, E. J. (2013). Phenolic profile and antioxidant activity of

various extracts from Citrullus colocynthis (L.) from the Pakistani flora. Industrial Crops and Products, 45, 416–422. doi: 10.1016/j.indcrop.2013.01.002

Folador, P., Cazarolli, L. H., Gazola, A. C., Reginatto, F. H., Schenkel, E. P., Silva, F. R. M. B. (2010). Potential insulin secretagogue effects of isovitexin

and swertisin isolated from Wilbrandia ebracteata roots in non–diabetic rats. Fitoterapia, 81 (8), 1180–1187. doi: 10.1016/j.fitote.2010.07.022

Stefanov, O. V. (2001). Doklinichni doslidzhennia likarskykh zasobiv. Kyiv: Avitsena, 527.

Tcyganenko, A. Ya., Zhukov, V. I., Leonov, V. V. et al. (2005). Klinicheskaia biokhimiia, 2–e izd.. Kharkov: Fakt, 454.

Stalnaia, I. D., Orekhovich, V. N. (1977). Sovremennye metody v biokhimii. Moscow: Meditcina, 66–67.

Koroliuk, M. A., Ivanova, A. I., Maiorova, I. T. et al. (1988). Laboratornoe delo, 1, 16–19.

Sirota, T. V. (1999). Voprosy meditcinskoi khimii, 3, 263–271.

Abd El–Baky, A. E., Amin, H. K. (2011). Effect of Citrullus colocynthis in ameliorate the oxidative stress and nephropathy in diabetic experimental

rats. IJPSR, 2 (2), 1–10.

Zamani, M., Rahimi, A. O., Mahdavi, R., Sarker, S. (2007). Assessment of antihyperlipidemic effect of Citrullus colocynthis. Rev. Bras. Farmacogn.,

(4), 492–496.

Dashti, N., Zamani, M., Mahdavi, R., Ostad Rahimi, A. (2012). The effect of citrullus colocynthis on blood glucose profile level in diabetic rabbits. J.

Jahrom Univ. Med. Sci., 9 (4), 24–28.

Lakshmi, B., Sendrayaperumal, V., Subramanian, S. (2013). Beneficial effects of Citrullus colocynthis seeds extract studied in alloxan–induced

diabetic rats. Int. J. Pharm. Sci. Rev. Res., 19 (1), 47–55.

Jeyanthi, K. A., Christy, A. M. V. (2009). Antihyperglycemic effect of Citrullus colocynthis seed powder in alloxan induced diabetic rats. IUP J. Biotechnol.,

(4), 30–36.

Salami, M., Aqanouri, Z., Karimian, M., Enshai, M. (2004). The hypoglycemic effect of Citrullus colocynthis in normal rats. IJPR, 3 (2), 50.

Jayaraman, R., Kumar, G. A. S., Raj, P. V., Naruanan, K. (2009). Hypoglycemic activity of methanolic extract of fruits of Citrullus colocynthis. Biomed.,

(3), 269–277.

Agarwal, V., Sharma, A. K., Upadhyay, A., Singh, G., Gupta, R. (2012). Hypoglycemic effects of Citrullus colocynthis roots. Acta Pol. Pharm., 69 (1), 75–79.

Marwat, S. K., Rehman, F., Khan, E. A. et al. (2014). Useful ethnophytomedicinal recipes of angiosperms used against diabetes in South East Asian

Countries (India, Pakistan & Sri Lanka). Pak. J. Pharm. Sci., 27 (5), 1333–1358.

Huseini, H. F., Darvishzadeh, F., Heshmat, R., Jafariazar, Z., Raza, M., Larijani, B. (2009). The clinical investigation ofcitrullus colocynthis(L.) schrad

fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo–controlled clinical trial. Phytotherapy Research, 23 (8), 1186–1189.

doi: 10.1002/ptr.2754

Benariba, N., Djaziri, R., Hupkens, E., Louchami, K., Malaisse, W. J., Sener, A. (2012). Insulinotropic action of Citrullus colocynthis seed extracts in

rat pancreatic islets. Molecular Medicine Reports, 7 (1), 233–236. doi: 10.3892/mmr.2012.1151

Bnouham, M., Ziyyat, A., Mekhfi, H., Abdelkhaleq, L. (2006). Medicinal plants with potential antidiabetic activity–a review of ten years of herbal

medicine research (1990–2000). Int. J. Diabetes Metab., 14, 1–25.

Ahangarpour, A., Oroojan, A. A. (2013). Effect of crust and seed hydro–alcoholic and aqueous extracts and pulp hydro–alcoholic extract of Citrullus

colocynthis on glucose, insulin and FIRI level in insulin resistant male rat’s. Horizon Med. Sci., 19 (3), 149–154.

Sebbagh, N., Cruciani–Guglielmacci, C., Ouali, F., Berthault, M.–F., Rouch, C., Sari, D. C., Magnan, C. (2009). Comparative effects of Citrullus colocynthis,

sunflower and olive oil–enriched diet in streptozotocin–induced diabetes in rats. Diabetes & Metabolism, 35 (3), 178–184. doi: 10.1016/j.


Dallak, M., Al–Khateeb, M., Abbas, M., Elessa, R., Al–Hashem, F., Bashir, N., Khalil, M. (2009). In vivo, Acute, Normo–hypoglycemic, Antihyperglycemic,

Insulinotropic Actions of Orally Administered Ethanol Extract of Citrullus colocynthis (L.) Schrab Pulp. American Journal of Biochemistry and

Biotechnology, 5 (3), 119–126. doi: 10.3844/ajbbsp.2009.119.126

Benariba, N., Bellakdhar, W., Djaziri, R., Hupkens, E., Louchami, K., Malaisse, W. J. (2012). Protective action of Citrullus colocynthis seed extracts

against the deleterious effect of streptozotocin on both in vitro glucose–stimulated insulin release from rat pancreatic islets and in vivo glucose

homeostasis. Biomedical Reports, 1 (1), 119–121. doi: 10.3892/br.2012.5

Jayaraman, R., Christina, A. J. M. (2013). Citrullus colocynthis attenuates hyperlipidemia and hyperglycemia through its antioxidant property

against hyperlipidemic and diabetic animal models. Der. Pharmacia Sinica, 4 (1), 60–66.

Dallak, M., Bashir, N., Abbas, M., Elessa, R., Haidara, M., Khalil, M., AL–Khateeb, M. A. (2009). Concomitant Down Regulation of Glycolytic Enzymes, Upregulation

of Gluconeogenic Enzymes and Potential Hepato–Nephro–Protective Effects Following the Chronic Administration of the Hypoglycemic, Insulinotropic

Citrullus colocynthis Pulp Extract. American Journal of Biochemistry and Biotechnology, 5 (4), 153–161. doi: 10.3844/ajbbsp.2009.153.161

Ebrahimi, E., Bahramzadeh, S., Hashemitabar, M., Mohammadzadeh, G., Shirali, S., Jodat, J. (2016). Effect of hydroalcoholic leaves extract of Citrullus

colocynthis on induction of insulin secretion from isolated rat islets of Langerhans. Asian Pacific Journal of Tropical Disease, 6 (8), 638–641.

doi: 10.1016/s2222–1808(16)61101–5

Sanadgol, N. A., Najafi, Sh., Ghasemi, L. V., Motalleb, G., Estakhr, J. (2011). A study of the inhibitory effects of Citrullus colocynthis (CCT) using hydro–

alcoholic extract on the expression of cytokines: TNF–α and IL–6 in high fat diet–fed mice toward sacure for diabetes mellitus. J. Pharmacogn.

Phytother., 3 (6), 81–88.

Shafaei, H., Rad, J., Behjati, M., Delazar, A. (2014). The effect of pulp and seed extract of Citrullus Colocynthis, as an antidaibetic medicinal herb, on

hepatocytes glycogen stores in diabetic rabbits. Advanced Biomedical Research, 3 (1), 258. doi: 10.4103/2277–9175.148230

Abdel–Hassan, I. A., Abdel–Barry, J. A., Tariq Mohammeda, S. (2000). The hypoglycaemic and antihyperglycaemic effect of Citrullus colocynthis fruit

aqueous extract in normal and alloxan diabetic rabbits. Journal of Ethnopharmacology, 71 (1–2), 325–330. doi: 10.1016/s0378–8741(99)00215–9

Benmehdi, H. (2011). Effect of saponosides crude extract isolated from Citrullus Colocynthis (L.) seeds on blood glucose level in normal and

streptozotocin induced diabetic rats. Journal of Medicinal Plants Research, 5 (31). doi: 10.5897/jmpr11.1369

Singh, L. W. (2011). Traditional medicinal plants of Manipur as antidiabetics. J. Med. Plant Res., 5 (5), 677–687.

Meena, M. C., Patni, V. (2008). Isolation and identification of flavonoid “quercetin” from Citrullus colocynthis (Linn.) Schrad. Asian J. Exp. Sci., 22 (1), 137–142.

Cazarolli, L. H., Folador, P., Moresco, H. H., Brighente, I. M. C., Pizzolatti, M. G., Silva, F. R. M. B. (2009). Stimulatory effect of apigenin–6–C–β–l–fucopyranoside

on insulin secretion and glycogen synthesis. European Journal of Medicinal Chemistry, 44 (11), 4668–4673. doi: 10.1016/j.ejmech.2009.07.001

Youl, E., Bardy, G., Magous, R., Cros, G., Sejalon, F., Virsolvy, A., Oiry, C. (2010). Quercetin potentiates insulin secretion and protects INS–1 pancreatic β–cells

against oxidative damage via the ERK1/2 pathway. British Journal of Pharmacology, 161 (4), 799–814. doi: 10.1111/j.1476–5381.2010.00910.x

Hussain, A. I., Rathore, H. A., Sattar, M. Z. A., Chatha, S. A. S., Sarker, S. D., Gilani, A. H. (2014). Citrullus colocynthis (L.) Schrad (bitter apple fruit): A review of

its phytochemistry, pharmacology, traditional uses and nutritional potential. Journal of Ethnopharmacology, 155 (1), 54–66. doi: 10.1016/j.jep.2014.06.011

Delazar, A., Gibbons, S., Kosari, A. R., Nazemiyeh, H., Modarresi, M., Nahar, L., Sarker, S. D. (2006). Flavone c–glycosides and cucurbitacin glycosides

from citrullus colocynthis. DARU, 14 (3), 109–114.

Nmila, R., Gross, R., Rchid, H., Roye, M., Manteghetti, M., Petit, P., Sauvaire, Y. (2000). Insulinotropic Effect of Citrullus colocynthis Fruit Extracts.

Planta Medica, 66 (5), 418–423. doi: 10.1055/s–2000–8586

Hediat, M. H. S. (2012). Alkaloids and flavonoids from the air dried aerial parts of Citrullus colocynthis. Journal of Medicinal Plants Research, 6 (38),

–5155. doi: 10.5897/jmpr12.406

Gentile, S., Turco, S., Guarino, G., Sasso, C. F., Amodio, M., Magliano, P., Torella, R. (2000). Comparative efficacy study of atorvastatin vs. simvastatin,

pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Diabetes, Obesity and Metabolism, 2 (6), 355–362.

doi: 10.1046/j.1463–1326.2000.00106.x

Jayaraman, R., Christina, A. J. M. (2013). Evaluation of Citrullus colocynthis fruits on in vitro antioxidant activity and in vivo DEN/PB induced

hepatotoxicity. IJARNP, 6 (1), 1–9.

Abou, A. R., Omayma, Z., Khalid, M. F., Aliaa, H. A. (2013). Biochemical effect of Citrullus colocynthis in experimental diabetes mellitus in rats.

Benha Vet. Med. J., 25 (1), 218–227.

Abe, I., Seki, T., Umehara, K., Miyase, T., Noguchi, H., Sakakibara, J., Ono, T. (2000). Green Tea Polyphenols: Novel and Potent Inhibitors of Squalene

Epoxidase. Biochemical and Biophysical Research Communications, 268 (3), 767–771. doi: 10.1006/bbrc.2000.2217

Harada, U., Chikama, A., Saito, S., Takase, H., Nagao, T., Hase, T., Tokimitsu, I. (2005). Effects of the Long–Term Ingestion of Tea Catechins on Energy

Expenditure and Dietary Fat Oxidation in Healthy Subjects. Journal of health science, 51 (2), 248–252. doi: 10.1248/jhs.51.248

Sheikhpour, R., Yaghmaei, P. (2012). A survey on herbal medicines for hypoglycemia in diabetic patients. Iran. J. Diabetes Obes., 4 (1), 40–49.

Yoshida, S., Hashimoto, T., Kihara, M., Imai, N., Yasuzaki, H., Nomura, K., Umemura, S. (2009). Urinary Oxidative Stress Markers Closely Reflect

the Efficacy of Candesartan Treatment for Diabetic Nephropathy. Nephron Experimental Nephrology, 111 (1), e20–e30. doi: 10.1159/000178764

Scheen, A. J. (2003). Treatment of type 2 diabetes. Acta Clinica Belgica, 58 (5), 318–324.

Gurudeeban, S., Ramanathan, T. (2010). Antidiabetic effect of Citrullus colocynthis in alloxan–induced diabetic Rats. Ethnopharmacology, 1 (1), 112.

Mohammad, D. (2013). In vivo, hypolipidemic and antioxidant effects of Citrullus colocynthis pulp extract in alloxan–induced diabetic rats. African

Journal of Biotechnology, 10 (48), 9898–9903. doi: 10.5897/ajb11.268

Jeyanthi, K. A., Christy, A. M. V. (2011). Antioxidant effect of Citrullus colocynthis on alloxan induced diabetic rats. Int. J. Pharm. Biol. Arch., 2 (2), 696–701.

Zaree, A. B., Fallahhossini, H., Sharifabady, R., Nourouzzadeh, A., Imani, H., Ghoshouni, H. (2007). The Effect of Citrullus Colocynthis Extract on

Preventing/ Reducing Streptozotocin– Induced Diabetes in Rat. Kowsar Medical Journal, 12 (1), 13–20.






Pharmacology and biochemistry