Antidiabetic effect of Coccinia grandis (L.) Voigt (Cucurbitales: Cucurbitaceae) on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolizing enzymes

Meenatchi Packirisamy , Purushothaman Ayyakkannu and Maneemegalai Sivaprakasam

Abstract
Coccinia grandis (L.) Voigt (Cucurbitales: Cucurbitaceae) is a climbing perennial herb, growing throughout India and it is widely used in the traditional treatment of diabetes. The aim of present study was to evaluate the antidiabetic potential of the mature unripe of Coccinia grandis in streptozotocin (STZ)-induced diabetic rats with special reference to carbohydrate metabolizing enzymes. The optimum dose of Coccinia grandis extract (GCE) was determined by oral glucose tolerance test. The effects of CGE were compared with glibenclamide. Oral administration of Coccinia grandis extract at a concentration of 250 mg/kg body weight once daily to diabetic rats for the period of 30 days resulted in significant reduction in the levels of plasma glucose and glycosylated hemoglobin. Administration of CGE showed a significant increase in the levels of glycolytic enzymes and glycogen content and decrease in the levels of gluconeogenic enzymes in the liver of diabetic treated rats. The anti-hyperglycemic effect of the extract was comparable with glibenclamide, a known hypoglycemic drug. Present findings provide experimental evidence that the fruits of C. grandis have potential antidiabetic activity which might be used as a functional food and safe remedy for the treatment of diabetes and associated complications.

Keywords
Coccinia grandis; Streptozotocin; Antihyperglycemic effect; Glibenclamide; Carbohydrate metabolizing enzymes.

DOI
10.21472/bjbs.051107

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References
Akhtar, M. A.; Rashid, M.; Wahed, M. I. I; Islam, M. R.; Shaheen, S. M.; Islam, M. A.; Amran, M. S.; Ahmed, M. Comparison of long term antihyperglycemic and hypolipidemic effects between Coccinia cordifolia (Linn.) and Catharanthus roseus (Linn.) in alloxan-induced diabetic rats. Research Journal of Medicine and Medical Sciences, v. 2, no. 1, p. 29-34, 2007.

Ali, L.; Khan, A. K.; Mamun, M. I.; Mosihuzzaman, M.; Nahar, N.; Nur-e-Alam, M.; Rokeya, B. Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats. Planta Medica, v. 59, no. 5, p. 408-412, 1993. https://doi.org/10.1055/s-2006-959720

Ambady, R.; Chamukuttan, S. Early diagnosis and prevention of diabetes in developing countries. Reviews in Endocrine and Metabolic Disorders, v. 9, no. 3, p. 193-201, 2008. https://doi.org/10.1007/s11154-008-9079-z

Ananda, P. K.; Kumarappan, C. T.; Sunil, C.; Kalaichelvan, V. K. Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats. Asian Asian Pacific Journal of Tropical Biomedicine, v. 2, no. 1, p. 31-35. 2012. https://doi.org/10.1016/S2221-1691(11)60185-8

Anhawange, A. A.; Ajibola, V. O.; Oniye, S. J. Chemical studies of seeds of Moronga oleifera (Lam) and Detarium microcarpum (Guill and Sperr). Journal of Biological Sciences, v. 4, p. 711-715, 2004. https://doi.org/10.3923/jbs.2004.711.715

Araki, E.; Haneda, M.; Kasuga, M.; Nishikawa, T.; Kondo, T.; Ueki, K.; Kadowaki, T. New glycemic targets for patients with diabetes from the Japan Diabetes Society. Journal of Diabetes Investigation, v. 8, no. 1, p. 123-125, 2017. https://doi.org/10.1111/jdi.12600

Asp, N. G.; Johansson, C. G.; Hallmer, H.; Siljestroem, M. Rapid enzymic assay of insoluble and soluble dietary fiber. Journal of Agricultural and Food Chemistry, v. 31, no. 3, p. 476-482, 1983. https://doi.org/10.1021/jf00117a003

Babu, P. S.; Prabuseenivasan, P; Ignacimuthu, S. Cinnamaldehyde: A potential antidiabetic agent. Phytomedicine, v. 14, p. 15-22, 2007. https://doi.org/10.1016/j.phymed.2006.11.005

Bergmeyer, U. Glucose 6-phosphate dehydrogenase. In: Bergmeyer, U. Methods of enzymatic analysis. 2. ed. New York: Academic Press, 1984. https://doi.org/10.1016/B978-0-12-091302-2.X5001-4

Bopanna, K. N.; Kannan, J.; Sushma, G.; Balaraman, R.; Rathod, S. P. Antidiabetic and antihyperlipidemic effects of neem seed kernel powder on alloxan diabetic rabbits. Indian Journal of Pharmacology, v. 29, no. 3, p. 162-167, 1997.

Brandstrup, N.; Kirk, J. E.; Brunic, C. Determination of glucokinase in tissues. Journal of Gerontology, v. 12, p. 166-171, 1957.

Bürgi, W.; Briner, M.; Franken, N.; Kessler, A. C. H. One-step sandwich enzyme immunoassay for insulin using monoclonal antibodies. Clinical Biochemistry, v. 21, no. 5, p. 311-314, 1988. https://doi.org/10.1016/S0009-9120(88)80087-0

Caengprasath, N.; Ngamukote, S.; Makynen, K.; Adisakwattana, S. The protective effects of pomelo extract (Citrus grandis L. Osbeck) against fructose-mediated protein oxidation and glycation. EXCLI Journal, v. 12, p. 491-502, 2013.

Chang, C.; Yang, M.; Wen, H.; Chern, J. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis, v. 10, no. 2, p. 178-182, 2002.

Drabkin, D. L.; Austin, J. M. Spectrophoto-metric studies, spectrophotometric constants for common haemoglobin derivatives in human, dog and rabbit blood. Journal of Biological Chemistry, v. 98, p. 719-733, 1932. Available from: <http://www.jbc.org/content/98/2/719.full.pdf+html>. Accessed on: Apr. 23, 2018.

Fuhlendorff, J.; Rorsman, P.; Kofod, H.; Brand, C. L.; Rolin, B.; MacKay, P.; Shymko, R.; Carr, R. D. Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes. Diabetes, v. 47, no. 3, p. 345-351, 1998. https://doi.org/10.2337/diabetes.47.3.345

Gancedo, J. M.; Gancedo, C. Fructose-1,6-diphosphatase, phosphofructokinase and glucose-6-phosphate dehydrogenase from fermenting and nonfermenting yeasts. Archiv für Mikrobiologie, v. 76, no. 2, p. 132-138, 1971. https://doi.org/10.1007/BF00411787

Gao, Z.; Yin, J.; Zhang, J.; Ward, R. E.; Martin, R. J.; Lefevre, M.; Cefalu, W. T.; Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes, v. 58, no. 7, p. 1509-1517, 2009. https://doi.org/10.2337/db08-1637

Harbourne, J. B. Phytochemical methods: A Guide to Modern Techniques of Plant Analysis. 3. en. London, UK: Chapman & Hall Pub; 1998.

Jayanthi, M.; Sowbala, N.; Rajalakshmi, G.; Kanagavalli, U.; Sivakumar, V. Study of antihyperglycemic effect of Catharanthus roseus in alloxan induced diabetic rats. International Journal of Pharmacy and Pharmaceutical Sciences, v. 2, suppl. 4, p. 114-116, 2010. Available from: <https://innovareacademics.in/journal/ijpps/Vol2Suppl4/818.pdf>. Accessed on: Apr. 23, 2018.

Joy, K. I.; Kuttan, R. Anti-diabetic activity of Picrorriza kurroa extract. Journal of Ethnopharmacology, v. 67, no. 2, p. 143-148, 1999. https://doi.org/10.1016/S0378-8741(98)00243-8

Kirana, H.; Srinivasan, B.P. Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in non insulin dependent diabetes mellitus induced rats. Indian Journal of Pharmacology, v. 40, no. 3, p. 103-106, 2008. https://doi.org/10.4103/0253-7613.42301

Koide, H.; Oda, T. Pathological occurrence of glucose-6-phosphatase in serum in liver diseases. Clinica Chimica Acta, v. 4, no. 4, p. 554-561, 1956. https://doi.org/10.1016/0009-8981(59)90165-2

Kumar, G. P.; Sudheesh, S.; Vijayalakshmi, N. R. Hypoglycaemic effect of Coccinia indica: Mechanism of action. Planta Medica, v. 59, no. 4 p. 330-332, 1993. https://doi.org/10.1055/s-2006-959693

Lowry, O. H.; Rosenbrough, N. J.; Farr, A. L.; Randall, R. J. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, v. 193, p. 265-275, 1951. Available from: <http://www.jbc.org/content/193/1/265.long>. Accessed on: Apr. 23, 2018.

McAnuff, M. A.; Omoruyi, F. O.; Morrison, E. Y.; Asemota, H. N. Changes in some liver enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from Bitter yam (Dioscorea polygonoides) or commercial diosgenin. West Indian Medical Journal, v. 54, no.2, p. 97-101, 2005.

Meenatchi, P.; Purushothaman, A.; Maneemegalai, S. Antioxidant, antiglycation and insulinotrophic properties of Coccinia grandis (L.) in vitro: Possible role in prevention of diabetic complications. Journal of Traditional and Complementary Medicine, v. 7, no. 1, p. 54-64, 2017. https://doi.org/10.1016/j.jtcme.2016.01.002

Morales, M. A.; Jabbay, A. J.; Tenenzi, H. P. Mutation affecting accumulation of glycogen. Neurospora Newsletter, v. 20, p. 24-25, 1975.

Mourya, P.; Shukla, A.; Rai, G.; Lodhi, S. Hypoglycemic and hypolipidemic effects of ethanolic and aqueous extracts from Ziziphus oenoplia (L) Mill on alloxan-induced diabetic rats. Beni-Suef University Journal of Basic and Applied Sciences, v. 6, p. 1-9, 2017. https://doi.org/10.1016/j.bjbas.2016.12.002

Mungole, A. J.; Awati, R.; Chaturvedi, A.; Zanwar, P. Preliminary phytochemical screening of Ipomoea obscura (L): A hepatoprotective medicinal plant. International Journal of PharmTech Research, v. 2, no. 4, p. 2307-2312, 2010. Available from: <http://sphinxsai.com/Oct_dec_2010_vol2_no.4/PharmTech_vol2_no.4_1_pdf/PT=28 (2307-2312).pdf>. Accessed on: Apr. 23, 2018.

Nayak, S. S.; Pattabiraman, T. N. A new colorimetric method for the estimation of glycosylated haemoglobin. Clinica Chimica Acta, v. 109, no. 3, p. 267-274, 1981. https://doi.org/10.1016/0009-8981(81)90312-0'

Nenna, A.; Nappi, F.; Avtaar Singh, S. S.; Sutherland, F. W.; Di Domenico, F.; Chello, M.; Spadaccio, C. Pharmacologic approaches against advanced glycation end products (AGEs) in diabetic cardiovascular disease. Research in Cardiovascular Medicine, v. 4, no. 2, e26949, 2015. https://doi.org/10.5812/cardiovascmed.4(2)2015.26949

Pari, L.; Rajarajeswari, N. Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats. Chemico-Biological Interactions, v. 181, no. 3, p. 292-296, 2009. https://doi.org/10.1016/j.cbi.2009.07.018

Pari, L.; Saravanan, R. Succinic acid monoethyl ester and metformin regulates carbohydrate metabolic enzymes and improves glycemic control in streptozotocin-nicotinamide induced type 2 diabetic rats. Iranian Journal of Pharmacology and Therapeutics, v. 4, p. 132-137, 2005. Available from: <http://ijpt.iums.ac.ir/article-1-57-en.pdf>. Accessed on: Apr. 23, 2018.

Ramesh, B.; Saravanan, B. R.; Pugalendi, K. V. Influence of sesame oil on blood glucose, lipid peroxidation and antioxidant status in streptozotocin diabetic rats. Journal of Medicinal Food, v. 8, no. 3, p. 377-381, 2005. https://doi.org/10.1089/jmf.2005.8.377

Shulman, G. I. Cellular mechanisms of insulin resistance. The Journal of Clinical Investigation, v. 106, p. 171-176, 2000. https://doi.org/10.1172/JCI10583

Singh, J.; Kakkar, P. Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. Journal Ethnopharmacology, v. 123, no. 1, p. 22-26, 2009. https://doi.org/10.1016/j.jep.2009.02.038

Singleton, V. L.; Orthofer, R.; Lamuela-Raventos, R. M. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. In: Packer, L. (Ed.). Methods in enzymology: Oxidant and antioxidants (Part A). San Diego, CA: Academic Press, 1999. p. 152-178.

Sirag, H. M. Biochemical and hematological studies for the protective effect of oyster mushroom (Pleurotus ostreatus) against glycerol-induced acute renal failure in rats. Journal of Biological Sciences, v. 9, p. 746-752, 2009. https://doi.org/10.3923/jbs.2009.746.752

Smith, J. G.; Yokoyama, W. H.; German, J. B. Butyric acid from the diet: Actions at the level of gene expression. Critical Reviews in Food Science and Nutrition, v. 38, p. 259-297, 1998. https://doi.org/10.1080/10408699891274200

Sofowora, A. Medicinal plants and traditional medicine in Africa. 2. ed. Nigeria, Ibadan: Spectrum Books, 1993.

Stamp, N. Out of the quagmire of plant defense hypotheses. The Quarterly Review of Biology, v. 78, p. 23-55, 2003.

Stefanović, O. D.; Tešić, J. D.; Ćomić, L. R. Melilotus albus and Dorycnium herbaceum extracts as source of phenolic compounds and their antimicrobial, antibiofilm, and antioxidant potentials. Journal of Food and Drug Analysis, v. 23, p. 417-424 2015. https://doi.org/10.1016/j.jfda.2015.01.003

Subramanian, R.; Asmawi, M. Z.; Sadikun, A. In-vitro α-glucosidase and α-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide. Acta Biochimica Polonica, v. 55, no. 2, p. 391-398, 2008. Available from: <http://www.actabp.pl/pdf/2_2008/391.pdf>. Accessed on: Apr. 23, 2018.

Thornalley, P. J. Dicarbonyl intermediates in the maillard reaction. Annals of the New York Academy Science, v. 1043, p. 111-117, 2005. https://doi.org/10.1196/annals.1333.014

Tiwari, A. K.; Rao, J. M. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: Present status and future prospects. Current Science, v. 83, p. 1-10, 2002. Available from: <http://www.iisc.ernet.in/currsci/jul102002/30.pdf>. Accessed on: Apr. 23, 2018.

Trinder, P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, v. 6, p. 24-27, 1969. https://doi.org/10.1177/000456326900600108

Venkateswaran, S.; Pari, L. Effect of Coccinia indica leaf extract on plasma antioxidants in Streptozotocin-induced experimental diabetes in rats. Phytotherapy Research, v. 17, p. 605-608, 2003. https://doi.org/10.1002/ptr.1195

Venkateswaran, S.; Pari, L. Effect of Coccinia indica on blood glucose, insulin and key hepatic enzymes in experimental diabetes. Pharmaceutical Biology, v. 3, p. 165-170, 2002. https://doi.org/10.1076/phbi.40.3.165.5836

Wei, M.; Ong, L.; Smith, M. T.; Ross, F. B.; Schmid, K.; Hoey, A. J.; Burstow, D.; Brown, L. The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes. Heart Lung and Circulation, v. 12, no. 1, p. 44-50, 2003. https://doi.org/10.1046/j.1444-2892.2003.00160.x

Welihinda, J.; Karunanayake, E. H.; Sheriff, M. H.; Jayasinghe, K. S. The effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. Journal of Ethnopharmacology, v. 17, no. 3, p. 277-282, 1986.

WHO - World Health Organization. Global report on diabetes. 1. Diabetes Mellitus - epidemiology. 2. Diabetes Mellitus - prevention and control. 3. Diabetes, gestational. 4. Chronic disease. 5. Public health. Geneva: WHO, 2016.

Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, v. 27, no. 5, p. 1047-1053, 2004. https://doi.org/10.2337/diacare.27.5.1047