EFFECT OF CENTELLA ASIATICA (LINN) LEAVES ON SELECTIVE MITOCHONDRIAL AND CYTOSOLIC ENZYMES IN STREPTOZOTOCIN INDUCED DIABETIC RATS
Keywords:Centella asiatica, Streptozotocin, Diabetes mellitus, Mitochondrial enzymes, Cytosolic enzymes
Objective: The objective of the study is to evaluate the therapeutic effect of Centella asiatica leaves by assaying the activities of selective mitochondrial and cytosolic enzymes in the streptozotocin induced diabetic rats.
Methods: The rats were divided into five groups of 6 rats in each group. The methanol extract of Centella asiatica leaves (CALEt) was orally administered at a dose of 300 mg/kg body weight (b. w). The activities of both mitochondrial and cytosolic enzymes viz succinate dehydrogenase (SDH), malate dehydrogenase (MDH), glutamate dehydrogenase (GDH), lactate dehydrogenase (LDH) and glucose 6 phosphate dehydrogenase (G6PDH) were measured in the liver and kidney of the experimental rats.
Results: Diabetic rats showed a significant (p<0.001) reduction in the activities of mitochondrial enzymes such as SDH, MDH and GDH. Furthermore, the cytosolic enzyme G6PDH activity was significantly (p<0.001) decreased along with a significant increase in the LDH activity in diabetic rats. The daily oral treatment of CALEt to diabetic rats for 30 d reversed the above changes in a significant (p<0.001) manner.
Conclusion: The results obtained in this study indicated that methanol extract of Centella asiatica leaves could restore the altered activities of mitochondrial and cytosolic enzymes, thereby suggesting its position in the energy production. Our data suggest that Centella asiatica leaves should be further explored for its role in the treatment of diabetes mellitus.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2095-128.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990â€“2010:a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2197-223.
An International Diabetes Federation (IDF) [Internet]. Country estimates table 2011. 6th ed. IDF diabetes atlas; 2012.
Wallace DC. Mitochondrial diseases in man and mouse. Science 1999;283:1482-8.
Lowell, BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005;307:384-7.
Albertoni Borghese MF, Balonga S, Lavagna A, Filipuzzi AL, Majowicz M, Bustamante J. Mitochondrial dysfunction in brain cortex mitochondria of stz-diabetic rats: Effect of l-arginine. Neurochem Res 2013;38:2570-80.
Toledo FG, Menshikova EV, Ritov VB, Azuma K, Radikova Z, DeLany J, et al. Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes. Diabetes 2007;56:2142-7.
Sachin Supale, Ning Li, Thierry Brun, Pierre Maechler. Mitochondrial dysfunction in pancreatic Î² cell. Trends Endocrinol Metab 2012;23:477-87.
Takizawa IT, Huang LU, Ikuta TZ, Yoshida LA. Human glucose-6-phosphate dehydrogenase primary structure and cDNA cloning. Natl Acad Sci USA 1986;83:265-73.
Hamilton JW, Jones FG, Mc Mulin MF. Glucose-6-phosphate dehydrogenase deficiency guadalajara-a case of chronic non-sperocytic haemolytic anaemia responding to splenectomy and the role of splenectomu in this disorder. Haematology 2004;9:307â€“9.
Murti Y, Singh AP, Pathak D. LC-MS/MS Profiling of hydroethanolic extract of Calotropis procera leaves. I Communique 2011;3:31-4.
Adeyi AO, Idowu AB, Mafiana CF, Oluwalana SA, Ajayi OL. Effects of aqueous leave extract of Ficus exasperata on pathophysiology and histopathogy of alloxan induced diabetic albino rats. J Med Plants Res 2012;6:5730-36.
James JT, Dubey IA. Pentacyclictriterpenoids from the medicinal herb, Centella asiatica (L) Urb. Molecules 2009;14:3922-41.
Goh SH. Malaysian medicinal plants for the treatment of cardiovascular diseases, Pelanduk Publications, Malaysia; 1995. p. 162.
Somara Sasikala, Siddamsetty Lakshminarasaiah, Malepati Dhananjaya Naidu. Antidiabetic activity of Centellaa siatica on streptozotocin induced diabetic male albino rats. World J Pharm Sci 2015;3:1701-5.
Vivek Kumar Sharma. Streptozotocin: an experimental tool in diabetes and Alzheimerâ€™s disease. Int J Res Dev 2010;2:1-7.
Virendra Singh, Mahendra Singh, Smita Shukla, Sunil Singh, Mohd Hashim Mansoori, Kori ML. Antidiabetic activity of Flacourita indica Merr in streptozotocin induced diabetic rats. Global J Pharmacol 2011;5:147-52.
Sabitha V, Ramachandran S, Naveen KR, Panneerselvam K. Antidiabetic and anti-hyperlipidemic potential of Abelmoschus esculentus Moench. In streptozotocin-induced diabetic rats. J Pharm Bioallsci 2011;3:397-402.
Nachlas MM, Margulies SI, Seligman AM. A colorimetric method for the estimation of succinic dehydrogenase activity. J Biol Chem 1960;235:499-503.
Lee YP, Lardy HA. Influence of thyroid hormones on L-Î±-glycerophosphate dehydrogenases and other dehydrogenases in various organs of the rat. J Biol Chem 1965;240:1427-36.
Bergmayer HU, Bruns E. Methods of enzymatic analysis, Academic Press: New York; 1965.
Prameelamma Y, Swami KS. Glutamate dehydrogenase activity in the normal and denervated gastrocnemius muscle of frog. Curr Sci 1975;44:739-40.
Steel RGD, Torrie JR. Principles and procedures of statistics with special reference to the biological sciences. McGraw, New York; 1960. p. 481.
Hayashi K, Kojima R, Ito M. Strain differences in the diabetogenic activity of streptozotocin in mice. Biol Pharm Bull 2006;29:1110-9.
Ito M. New model of progressive non-insulin-dependent diabetes mellitus in mice induced by streptozotocin. Biol Pharm Bull 1999;22:988-9.
Ikebukuro K, Adachi Y, Yamada Y, Fujimoto S, Seino Y, Oyaizu H. Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats. Transplantation 2002;73:512-8.
Michelakis ED, Hamp V, Nsair A, Wu X, Harry G, Haromy A, et al. Diversity in mitochondrial function explains differences in vascular oxygen sensing. Circ Res 2002;90:1307-15.
Nukatsuka M, Yoshimura Y, Nishida M, Kawada J. Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin in vivo study. J Pharmacobiodyn 1990;13:259-62.
Turk L, Corbett JA, Ramanadham S, Bohrer A, MC Daniel L. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commum 1993;197:1458-64.
Lenaz G. The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 2001;52:159-64.
Ceriello A. New insights on oxidative stress and diabetic complications may lead to a causalâ€ antioxidant therapy. Diabetes Care 2003;26:1589-96.
Aragno M, Mastrocola R, Alloatti G, Vercellinatto I, Bardini P, Geuna S, et al. Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinol 2008;149:380-8.
Puckett SW, Reddy WJ. A decrease in the malate-aspartate shuttle and glutamate translocase activity in heart mitochondria from alloxan-diabetic rats. J Mol Cell Cardiol 1979;11:173-87.
Sener A, Rasschaert J, Malaisse WJ. Hexose metabolism in pancreatic islets. Participation of Ca2 (+)-sensitive 2-ketoglutarate dehydrogenase in the regulation of mitochondrial function. Biochim Biophys Acta 1990;10:42-50.
Akude E, Zherebitskaya E, Chowdhury SK, Smith DR, Dobrowsky RT, Fernyhough P. Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats. Diabetes 2011;60:288-97.
Chowdhury SK, Zherebitskaya E, Smith DR, Akude E, Chattopadhyay S, Jolivalt CG, et al. Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment. Diabetes 2010;59:1082-91.
Murray RK, Granner DK, Mayes PA, Rodwell VW. Harperâ€™s Biochemistry. 24th edn. Prentice Hall, Englewood Cliffs, NJ; 1998.
Senthilkumar GP, Subramanian S. Biochemical evaluation of mitochondrial protective effect of Terminalia chebula studied in stz-Induced diabetic rats. Int J Biol Chem 2007;1:131-40.
Rajeswara Reddy S, Lavany T, Ganapathi Narasimhulu KS. Effect of pimpinella tirupatiensis on oxidative enzymes in STZ-induced diabetic rat kidney. Iran J Pharm Res 2012;11:277.
Charles Stanley. Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. Am J Clin Nutr 2009;90:862Sâ€“6S.
Ramudu SK, Korivi M, Kesireddy N, Lee LC, Cheng IS, Kuo CH, et al. Nephro-protective effects of a ginger extract on cytosolic and mitochondrial enzymes against streptozotocin (stz)-induced diabetic complications in rats. Chin J Physiol 2011;54:79-86.
Dudley GA, Staron RS, Murray TF, Hagerman FC, Luginbuhl A. Muscle fiber composition and blood ammonia levels after intense exercise in humans. J Appl Physiol: Respir Environ Exercise Physiol 1983;54:582-6.
Butt AA, Michaels S, Greer D, Clark R, Kissinger P, Martin DH. "Serum LDH level as a clue to the diagnosis of histoplasmosis". AIDS Read 2002;12:317-21.
Ainscow EK, Zhao C, Rutter GA. Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion. Diabetes 2000;49:1149-55.
Farswan M, Mazumder PM, Percha V. Protective effect of Cassia glauca Linn on the serum glucose and hepatic enzymes level in streptozotocin induced NIDDM in rats. Indian J Pharmacol 2009;41:19-22.
Patel SS, Goyal RK. Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit. Exp Clincardiol 2011;16:87-91.
Chang AY, Schneider DI. Blood glucose and gluconeogenic enzymes. Biochem Biophys Acta 1972;200:567-8.
Shailey S, Basir SF. Strengthening of antioxidant defense by Azadirachta indica in alloxan-diabetic rat tissues. J Ayurveda Integrative Med 2012;3:130-5.
Wan GH, Tsai SC, Chiu DT. Decreased blood activity of glucose-6-phosphate dehydrogenase associated with increased risk of diabetes mellitus. Endocrine 2002;19:191-5.
Diaz-Flores MMA, Ibanez-Hernandez RE, Galvan M, Gutierrez G, Duran-Reyes R, Medina-Navarroo D, et al. Glucose-6-phosphotase dehydrogenase activity and NADPH/NADP+ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat. Life Sci 2006;78:2601-7.
Rao NK, Bethala K, Sisinthy SP, Rajeswari KS. Antidiabetic activity of Orthosiphon stamineus benth roots in streptozotocin induced type 2 diabetic rats. Asian J Pharm Clin Res 2013;7:149-53.
Flavia OL, Fabiana RN, Ricardo DC, Jose MBF, Xirley PN, Ricardo RS, et al. Mechanisms involved in the antinociceptive effects of 7-Hydroxycoumarin. J Nat Prod 2011;74:596-602.