ABSTRACT Momordica Charantia (MC) is one of the most famous traditional plant worldwide, used for the treatment of diabetes and its complications. In the present study possible protective effect of MC in Streptozotocin (STZ) induced diabetic neuropathy in mice was evaluated. STZ induced diabetic mice were orally administered MC at various doses (200 - 800 mg/kg) for six weeks. Diabetes induced neuropathic pain was assessed by hot plate test, formalin test and tail flick test at the beginning and end of the study. Serum TBARS, NO and SOD levels were estimated at the end of the study as the markers of oxidative-nitrosative stress. Rotarod test was employed to assess the effect of treatment on motor coordination. The results showed that STZ induced diabetes significantly decreased the pain threshold as was indicated by increased flinching in formalin test and decreased withdrawal latency in hot plate and tail flick tests. Oxidative-nitrosative stress was significantly increased in diabetic animals. Chronic administration of MC significantly attenuated diabetes induced increase in flinches and decrease in withdrawal latency without impacting sensory and motor functions. MC administration also exhibited dose dependant reduction of hyperglycemia and serum TBARS, NO and SOD levels in diabetic mice. The results suggest that long term use of MC protects against diabetes induced neuropathy in association with attenuation of hyperglycemia and oxidative-nitrosative stress.
Cite this paper
Malik, Z. , Tabassum, N. and Sharma, P. (2013) Attenuation of experimentally induced diabetic neuropathy in association with reduced oxidative-nitrosative stress by chronic administration of Momordica charantia. Advances in Bioscience and Biotechnology, 4, 356-363. doi: 10.4236/abb.2013.43047.
 Tahrani, A.A., Askwith, T. and Stevens, M.J. (2010) Emerging drugs for diabetic neuropathy. Expert Opinion on Emerging Drugs, 15, 661-683.
 Al-Wahbi, A.M. (2010) Impact of a diabetic foot care education program on lower limb amputation rate. Vascular Health and Risk Management, 6, 923-934.
 Ziegler, D. (2008) Treatment of diabetic neuropathy and neuropathic pain: How far have we come? Diabetes Care, 3, S255-S261.
 Tavakoli, M. and Malik, R.A. (2008) Management of painful diabetic neuropathy. Expert Opinion on Pharmacotherapy, 9, 2969-2978.
 Bouton, A.J.M. (2005) Opoids for painful diabetic neuropathy. Current Diabetes Reports, 5, 407-408.
 Coppey, L.J., Gel-lett, J.S., Davidson, E.P., Dunlap, J.A., Lund, D.D. and Yorek, M.A. (2001) Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes, 50, 1927-1937.
 Cameron, N.E., Tuck, Z., McCabe, L. and Cotter, M.A. (2001) Effect of the hydroxyl radical scavenger, dimethylthiourea, on pe-ripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes. Diabetologia, 44, 1161-1169.
 Obrosova, I.G., Mab-ley, J.G., Zsengeller, Z., Charniauskaya, T., Abatan, O.I., Groves, J.T. and Szabo, C. (2005) Role for nitrosative stress in diabetic neuropathy: Evidence from studies with a peroxynitrite decomposition catalyst. FASEB Journal, 19, 401-403.
 Winkler, G. and Kempler, P. (2010) Pathomechanism of diabetic neuropathy: Background of the pathogenesis-oriented therapy. Orvosi Hetilap, 151, 971-981.
 Vallianou, N., Evangelopoulos, A. and Koutalas, P. (2009) Alpha-lipoic Acid and diabetic neuropathy. Review of Diabetes Studies, 6, 230-236.
 Malik, Z.A., Singh, M. and Sharma, P.L. (2011) Neuro-protective effect of Momordica charantia in global cerebral ischemia and re-perfusion induced neuronal damage in diabetic mice. Journal of Ethnopharmacology, 133, 729-734. doi:10.1016/j.jep.2010.10.061
 Marles, R. and Farnsworth, N. (1997). Antidiabetic plants and their active constituents: An update. Phytomedicine, 2, 137-189. doi:10.1016/S0944-7113(11)80059-0
 Basch, E., Gabardi, S. and Ulbricht, C. (2003) Bitter Melon (Mo-mordica charnatia): A review of efficacy and safety. American Journal of Health-System Pharmacy, 60, 356-359.
 Grover, J.K. and Yadav, S.P. (2004) Pharmacological actions and potential uses of Momordica charantia: A review. Journal of Ethnopharmacology, 93, 123-132.
 Matsuda, H., Li, Y., Murakami, T., Matsumura, N., Yamahara, J. and Yoshikawa, M. (1998) Antidiabetic principles of natural medicines. III. Structure-related inhibittory activity andmodeof action of oleanolic acid glycosides on hypoglycemic activity. Chemical and Pharmaceutical Bulletin (Tokyo), 46, 1399-1403.
 Myojin, C., Enami, N., Nagata, A., Yamaguchi, T., Takamura, H. and Matoba, T. (2008) Changes in the radical-scavenging activity of bitter gourd (Momordica charantia L.) during freezing and frozen storage with or without blanching. Journal of Food Science, 73, C546-C550. doi:10.1111/j.1750-3841.2008.00886.x
 Grover, J.K., Rathi, S.S. and Vats, V.V. (2002) Amelieration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucurana puriens and Tinospora cordifolia) extracts. Indian Journal of Experimental Biology, 40, 273-276.
 Evans, W.C. (1989) Trease and Evans’ pharmacognosy, 13th Edition, Bailliere Tindall, London.
 Rerup, C. and Tarding, F. (1969) Streptozotocin- and alloxan-diabetes in mice. European Journal of Pharma- cology, 7, 89-96. doi:10.1016/0014-2999(69)90169-1
 Eddy, N.B. and Leimbach, D.J., (1953) Synthetic analgesics. II. Dithie-nylbutenyl- and dithienylbutylamines. Journal of Pharmacology and Experimental Therapeutics, 107, 385-393.
 Tjolsen, A., Berge, O.G., Hunskaar, S., Rosland, J.H. and Hole, K. (1992) The formalin test: An evaluation of the method. Pain, 51, 5-17.
 D’Armour, W.L. and Smith, D.L. (1941) A method for determining loss of pain sensation. Journal of Pharmacology and Experimental Therapeutics, 72, 74-79.
 Dunham, N.W. and Miya, T.S. (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. Journal of American Pharmaceitocal Association. American Pharmaceutical Association, 46, 208-210.
 Sastry, K.V., Moudgal, R.P., Mohan, J., Tyagi, J.S. and Rao, G.S. (2002) Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Analytical Biochemistry, 306, 79-82.
 Ma, F.X., Liu, L.Y. and Xiong, X.M. (2003) Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein. Acta Pharmacologica Sinica, 24, 1027-1032.
 Misra, H.P. and Fridovich, I. (1971) The generation of superoxide radical during the autoxidation of ferredoxin. Journal of Biological Chemistry, 246, 6886-6890.
 Jewett, S.L. and Rocklin, A.M. (1993) Variation in one unit of activity with oxidation rate of organic substrate in indirect superoxide dismutase assays. Analytical Biochemistry, 212, 555-559. doi:10.1006/abio.1993.1368
 Obrosova, I.G., Mabley, J.G., Zsengeller, Z., Charniauskaya, T., Abatan, O.I., Groves, J.T. and Szabo, C. (2005) Role for nitrosative stress in diabetic neuropathy: Evidence from studies with a peroxynitrite decomposition catalyst. FASEB Journal, 19, 401-403.
 Grover, V.S., Sharma, A. and Singh, M. (2000) Role of nitic oxide in diabetes induced attenuation of antino- ciceptive effect of morphine in mice. European Journal of Pharmacology, 399, 161-164.
 Pop-Busui, R., Sima, A. and Stevens, M. (2006) Diabetic neuropathy and oxidative stress. Diabetes Metabolism Research and Reviews, 22, 257-273.
 Dib, M., Garrel, C., Favier, A., Robin, V. and Desrualla, C. (2002) Can malondialdehyde be used as a biological marker of progression in neurodegenerative disease? Journal of Neuroscience, 249, 367-374.
 Marletta, M.A., Yoon, P.S., Iyenger, R., Leaf, C.D. and Wishnok, J.S. (1988) Macrophage oxidation of L-arginine to nitrite and nitrate: Nitric oxide is an intermediate. Biochemistry, 27, 8706-8711. doi:10.1021/bi00424a003
 Aquilano, K. Baldelli, S. Cardaci, S., Rotilio, G. and Ciriolo, M.R. (2011) Nitric oxide is the primary mediator of cytotoxicity induced by GSH depletion in neuronal cells. Journal of cell Science, 124, 1043-1054.
 Forman, L.J., Estilow, S., Lewis, M. and Vasilenko, P. (1986) Streptozocin diabetes alters immunoreactive beta- endorphin levels and pain perception after 8 wk in female rats. Diabetes, 35, 1309-1313.
 Ohsawa, M. and Kamei, J. (1999) Possible involvement of spinal protein kinase C in thermal allodynia and hyperalgesia in diabetic mice. European Journal of Pharmacology, 372, 221-228.
 Wolff, S.P. (1987) The potential role of oxidative stress in diabetes and its complications: Novel Implication for theory and therapy. In: Crabba, M.J.C., Ed., Diabetic Complication: Scientific and Clinical Aspects, Churchill- Livingstone, New York, 167-200.
 Eriksson, U.J. and Berg, L.A.H. (1993) Diabetes and embryonic malformation role of substrate-induced free oxygen radical production for dysmorphogenesis in cultured rat embryos. Diabetes, 42, 411-419.
 Calles-Escandon, J. and Cipolla, M. (2001) Diabetes and endothelial dysfunction: A clinical perspective. Endocrine Reviews, 22, 36-52. doi:10.1210/er.22.1.36
 Cosentino, F., Hishikawa, K., Katusic, Z.S. and Luscher, T.F. (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation, 96, 25-28.
 Grover, J.K., Vats, V., Rathi, S.S. and Dawar, R. (2001) Traditional Indian anti-diabetic attenuate progression of renal damage in streptozotocin induced diabetic mice. Journal of Ethno-pharmacology, 76, 233-238.
 Srivastava, Y., VenkataKrishna-bhatt, H., Verma, Y. and Prem, S. (1987) Retardation of retinopathy by Momordica charantia L. (Bitter gourd) fruit extract in alloxan diabetic rats. Indian Journal of Experimental Biology, 25, 571-572.
 Welihinda, J., Karunanayake, E.H., Sheriff, M.H. and Jayasinghe, K.S. (1986) Effect of Momordica charantia of the glucose tolerance in maturity onset diabetes. Journal of Ethnopharmacology, 17, 277-282.
 Shibib, B.A., Khan, L.A. and Rahman, R. (1993) Hypoglycemic ac-tivity of Coccinia indica and Momordica charantia in diabetic rats: Depression of hepatic gluconeogenesis en-zymes glucose-6-phosphatase and fructose 1,6-bisphosphatase and elevation of both liver and red cell shunt enzyme glucose-6-phosphate dehydrogenase. Biochemical Journal, 292, 267-270.
 Ahmed, I., Adeghate, E., Sharma, A.K., Pallot, D.J. and Singh, A. (1998) Effect of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin diabetic rat. Diabetes Research and Clinical Practice, 40, 145-151.
 Rathi, S.S., Grover, J.K. and Vats, S. (2002) The effect of Momordica charantia and Mucuna puriens in experimental diabetes and their effect on key metabolic enzymes involved in carbohydrate metabolism. Phytotherapy Research, 16, 236-243. doi:10.1002/ptr.842