Momordica cymbalaria fruit extract attenuates high-fat diet-induced obesity and diabetes in C57BL/6 mice

Document Type: Short Communication


1 Department of Biotechnology, Padmashree Institute of Information Sciences, Bengaluru, Karnataka, India

2 Connexios Life Sciences Pvt. Ltd., Bengaluru, Karnataka, India

3 Department of Microbiology and Biotechnology, Bangalore University, Bengaluru, Karnataka, India

4 Independent Researcher, Kengeri, Bangalore, Karnataka, India

5 Radiant Research Services Pvt. Ltd., Bengaluru, Karnataka, India


Objective(s): The present study was aimed to evaluate the effect of methanolic fruit extract of Momordica cymbalaria (MeMC) against high-fat diet-induced obesity and diabetes in C57BL/7 mice.
Materials and Methods: In the present study, six weeks old male C57BL/6 mice were divided into four groups. G-1 and G-2 served as lean control and HFD control, G-3 and G-4 received MeMC 25 and 50 mg/kg, BW doses; all the treatments were given for a period of 11 weeks. The parameters such as body weight, fasting blood glucose, insulin, cholesterol, free fatty acid, and oral glucose tolerance tests were performed, further, at the end of the study fasting body weight, and weights of organs such as the liver, heart, and adipose tissue were measured and the liver tissue was subjected to histopathology evaluation, and insulin resistance was expressed as HOMA-IR index.
Results: The high-fat diet fed C57 mice showed significant elevation of body weight (P<0.01), blood glucose (P<0.01), insulin (P<0.01), cholesterol (P<0.01), free fatty acid (P<0.01), and HOMA-IR index (P<0.01) along with significant elevation of all organ weights and reduction in oral glucose tolerance (P<0.01) and brown adipose weight (P<0.01). The histopathology showed significant fatty infiltration and hypertrophy of hepatocytes. Interestingly, MeMC (50 mg/kg) alleviated all the HFD-induced perturbances significantly. Further, the HPLC analysis of MeMC revealed the presence of gallic acid and rutin as chief ingredients.
Conclusion: MeMC possesses potent antidiabetic activity and ameliorates insulin resistance in HFD diet fed C57 mice.


Main Subjects

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33: S62–S69.
2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes estimates for 2000 and projections for 2030. Diabetes care 2004 ;27:1047-1053.
3. Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev 2004; 3:CD003642.
4. Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 2007; 40: 163–173.
5. Dwivedi S, Daspaul A. Antidiabetic herbal drugs and polyherbal formulation used for diabetes: A review. J Phytopharmacol 2013;2: 44–51.
6. Chawla R, Thakur P, Chowdhry A, Jaiswal S, Sharma A, Goel R, Sharma J, Priyadarshi SS, Kumar V, Sharma RK, Arora R. Evidence based herbal drug standardization approach in coping with challenges of holistic management of diabetes: a dreadful lifestyle disorder of 21st century. J Diabetes Metab. Disord 2013; 12:35.
7. Wadood A, Wadood N, Shah SA. Effects of Acacia arabica and Caralluma edulis on blood glucose levels on normal and alloxan diabetic rabbits. J Pak Med Assoc 19889; 39: 208–212.
8. Karunanayake EH, Welihinda J, Sirimanne SR, Sinnadorai G. Oral hypoglycemic activity of some medicinal plants of Sri Lanka. J Ethnopharmacol 1984; 11:223–231.
9. Kumari K, Mathew BC, Augusti KT. Antidiabetic and hypolipidaemic effects of S-methyl cysteine sulfoxide, isolated from Allium cepa Linn. Indian J Biochem Biophys 1995; 32: 49–54.
10. Chattopadhyay RR, Chattopadhyay RN, Nandy AK, Poddar G, Mitra SK. Preliminary report on anti- hyperglycemic effect of fraction of fresh leaves of Azadiracta indica (Beng neem). Bull Calcutta Sch Trop Med 1987; 35:29–33.
11. Chattopadhyay RR, Chattopadhyay RN, Nandy AK, Poddar G, Mitra SK. The effect of fresh leaves of Azadiracta indica on glucose uptake and glycogen content in the isolated rat hemidiaphragm. Bull Calcutta Sch Trop Med 1987; 35:8–12.
12. Pari L, Amarnath SM. Antidiabetic activity of Boerhavia diffusa L. effect on hepatic key enzymes in experimental diabetes. J Ethnopharmacology 2004; 91:109–113.
13. Dhanabal SP, Sureshkumar M, Ramanathan M, Suresh B. Hypoglycemic effect of ethanolic extract of Musa sapientum on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. J Herb Pharmacother 2005; 5:7–19.
14. Pari L, Umamaheswari J. Antihyperglycaemic activity of Musa sapientum flowers: effect on lipid peroxidation in alloxan diabetic rats. Phytother Res 2000; 14:136–138.
15. Sabu MC, Kuttan R. Antidiabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol 2002; 81:155–160.
16. Adallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Ind J Exp Biol 2000; 38:607–609.  
17. Rao BK, Kesavulu MM, Giri R, Appa Rao C. Antidiabetic and hypolipidemic effects of Momordica cymbalaria Hook. fruit powder in alloxan-diabetic rats. J Ethnopharmacol 1999; 67: 103-109.
18. Rao BK, Kesavulu MM, Giri R, Appa Rao C. Antihyperglycemic activity of Momordica cymbalaria in alloxan diabetic rats. J Ethnopharmacol 2001; 78:67-71.
19. Rao BK, Kesavulu MM, Appa Rao C. Evaluation of antidiabetic effect of Momordica cymbalaria fruit in alloxan-diabetic rats. Fitoterapia 2003;74: 7-13.
20. Prashanth SJ, Suresh D, Maiya PS. In vitro antioxidant studies of Momordica cymbalaria. Asian J BioScie 2013; 8: 107-116.
21. Dhasan PB, Jegadeesan M, Kavimani S. Antiulcer activity of aqueous extract of fruits of Momordica cymbalaria Hook f. in Wistar rats. Pharmacog Res 2010; 2:58-61.
22. Marella S, Maddirela DR, Badri KR, Jyothi Kumar MV, Chippada A. Antihyperlipidemic and biochemical activities of Mcy protein in streptozotocin induced diabetic rats. Cell Physiol Biochem 2015; 35:1326-1334.
23. Murthy NS, Snehalatha N, Anuradha N, Seetharam YN. Anticonvulsant activity of ethanolic extract of Momordica cymbalaria Fenzl. ex Naud. Focus Altern Complement Ther 2007; 12:45-47.
24. Koneri RB, Samaddar S, Simi SM, Rao ST. Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy. Ind J Pharmacol 2014; 46:76-81.
25. Mahesh Kumar P, Venkataranganna MV, Manjunath K, Viswanatha GL, Ashok G. Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4. Chin J Nat Med 2014; 12: 895-900.                                     
26. Mahesh Kumar P, Venkataranganna MV, Manjunath K, Viswanatha GL, Ashok G. Methanolic fruit extract  of Momordica cymbalaria alleviates insulin resistance by enhancing expression of adiponectin and leptin in vitro. World J Pharm Pharm Sci 2016; 5:1925-1935.
27. OECD 2001. Guideline on acute oral toxicity (AOT) Environmental health and safety monograph series on testing and adjustment No.425.
a. e t y / r i s k -assessment/1948378.pdf. Accessed 23 Aug 2017.
28. Speakman J, Hambly C, Mitchell S, Krol E. Animal models of obesity. Obes Rev 2007; 8:55–61.
29. Johnson PR, Greenwood MR, Horwitz BA, Stern JS. Animal models of obesity: genetic aspects. Annu Rev Nutr 1991;11: 325–353.
30. Wang CY, Liao JK. A mouse model of diet-induced obesity and insulin resistance. Methods Mol Biol 2012; 821: 421–433.
31.Gisela W. Insulin and insulin resistance. Clin Biochem Rev 2005; 26: 19–39.
32. Wallace TM, Levy JC, Matthews DR. Use and Abuse of HOMA Modeling Diabetes Care 2004; 27: 1487-1495.
33. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003; 52:1655–1663.
34. Bouskila M, Pajvani UB, Scherer PE. Adiponectin: a relevant player in PPAR-γ agonist mediated improvements in hepatic insulin sensitivity?. Int J Obes 2005; 1:S17–S23.
35. Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin. Endocrinol 2006; 64:355–365.
36. Zheng F, Zhang S, Lu W, Wu F, Yin X, Yu D, Pan Q, Li H.  Regulation of insulin resistance and adiponectin signaling in adipose tissue by liver X receptor activation highlights a cross-talk with PPARγ. PLoS One 2014; 9: e101269.
37. Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004; 23:337–350.
38. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432.
39. Farooqi IS, Matarese G, Lord GM. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110:1093–1103.
40. Snehal SP, Goyal RK. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats, Pharmacog Res 2011; 3:239–245.
41. Li L,  Chen H, McGee SL. Mechanism of AMPK regulating GLUT4 gene expression in skeletal muscle cells. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2008; 25: 161-167.
42. Cai Y,  Fan C,  Yan J, Tian NX Effects of rutin on the expression of PPARγ in skeletal muscles of db/db mice. Planta Med 2012; 78:861-865.
43. Hsu CY,  Shih HY, Chia YC, Lee CH,  Ashida H, Lai YK, Weng CF. Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation. Mol Nutr Food Res 2014;58:1168-1176.  
44. Naowaboot J, Chung CH, Choi R. Rutin stimulates adipocyte differentiation and adiponectin secretion in 3T3-L1 adipocytes. J Med Assoc Thailand 2015; 98: S1-S6.