Supplementation of Corosolic acid prevents the devel-opment of Neuropathic pain in Streptozotocin induced diabetic rats



Objective:  The present study was designed to screen the neuroprotective and antioxidant activity of corosolic acid in painful diabetic neuropathy (DN).

Methods: Diabetes was induced in rats by a single dose of STZ (60mg/kg, i.p). Diabetic rats were tested every week for the development of pain, at the 5th week, rats showed sensations of pain. At the 6th week the rats developed significant neuropathic pain. They were divided into different groups and treated with Corosolic acid (2 and 4 mg/kg, p.o) for a further two weeks. The pain was assessed in the diabetic rats by mechano-tactil allodynia, mechanical hyperalgesia and cold allodynia. At the end of the treatment period the rats were scarified and biochemical changes such as their plasma glucose level, endogenous antioxidants (Lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) in sciatic nerve were evaluated. Further Na+/K+ ATPase and nitric oxide content was also evaluated.

Results: Treatment with the corosolic acid for two weeks restored their altered body weight and elevated blood sugar levels. Further corosolic acid showed a dose dependent reduction in pain in neuropathic animals. The level of endogenous antioxidants enzymes, Na+/K+ ATPase and nitric oxide were significantly prevented.

Conclusions: The result of the present study suggests the antidiabetic, antioxidant and neuroprotectieve property of corosolic acid in diabetic rats with neuropathic pain.

Full Text:



Bril V. Treatment of Diabetic Neuropathy. J Pe-riphera Nerv Sys. 2012; 2 (1), 22-27.

Hosseini A, Mahammad M. Diabetic Neuropathy and Oxidative stress: Therapeutic Perspective. Ox-id Med Cell Longev. 2013,1-15.

Thiticornpong W. Pharmacognostic evaluations of Lagerstroemia speciosa leave. J Med Plants Res. 2011, 5(8), 1330-37.

Judy WV, Hari SP, Stogsdill WW, Judy JS, Naguib YM, Passwater R. Antidiabetic activity of a stand-ardized extract (glucosol) from Lagerstroemia spe-ciosa leaves in type II diabetics.

A dose-dependence study. J Ethnopharmacol. 2003, 87,115–117.

Yamaguchi YU, Yamada K, Yoshikawa N, Naka-mura K,Haginaka J,Kunitoma M. Corosolic acid prevents oxidative stress, inflammation and hyper-tension in SHR/NDmcr-cp rats, a model of meta-bolic syndrome. Life Sci. 2006, 79, 2474-79, 2006.

Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksha TL. Quantitative assessment of tactile al-lodynia in the rat paw. J Neurosci Meth. 1994, 53, 55-63.

Shao-rui C, Samoriski G, Hui-lin P. Antinocicep-tive effect of chronic administration of uncompeti-tive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacol. 2009, 57,121-126.

Naik AK, Tandan SK, Dudhgaonkar SP, Jadhav SH, Kataria M, Prakash VR, et al. Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-l-cysteine in rats. Eur J Pain.2006, 10 (7), 573-9.

Slater TF, Sawyer BC. The stimulatory effect of carbon tetrachloride and other halogenalkane or peroxidative reaction in the rat liver functions in vitro. Biochem J. 1971, 123, 805-815.

Moron MS, Depierre JW. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Bio-chimbiophis Acta. 1979, 582, 67-78.

Misera HP, Fridovich I. The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for SOD. The J Biol Chem .1972, 247,3170–5.

Aebi H. Catalase in vivo. Methods Enzymol. 1984,105,121-126.

Bonting SL. Presence of enzyme system in mam-malian tissues. Membrane and ion transport. Wiley Int Sci. 1970, 257–63.

I. Guevara, J, Iwanejko A, Dembinska-Kiec J, Pankiewicz A, Wanat PA et al. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clinica Chimica Acta. 1998, 274, 177-88.

Kandhare AD, Raygude KS, Ghosh P, Bodhankar SL. The ameliorative effect of fisetin, a bioflavo-noid, on ethanol-induced and pylorus ligation-induced gastric ulcer in rats. Int J Green Pharm. 2011, 5, 236–43.

Negi G, Kumar A, Kundal RK, Gulati A, Sharma SS. Functional and biochemical evidence indicat-ing beneficial effect of melatonin and Nicotina-mide alone and in combination in experimental di-abetic neuropathy. Neuropharmacol.2010,58, 585-592.

Anjaneyulu M, Chopra K. Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephrop-athy in rats. Clin Exp Pharmacol Physiol. 2004, 31, 244–8.

Mahesh T, Menon VP. Quercetin allievates oxida-tive stress in streptozotocin induced diabetic rats. Phytother Res. 2004, 18(2), 123–7.

Sharma S, Kulkarni SK, Chopra K. Resveratrol, a polyphenolic phytoalexin attenuates thermal hy-peralgesia and cold allodynia in STZ induced dia-betic rats. Ind J Exp Biol. 2006, 44,566–9.

Klein G, Kim J, Himmeldirk K, Cao Y, Chen X. Antidiabetic and anti-obesity activity of Lager-stroemia speciosa. Evid Based Complement Alter-nat Med. 2007, 4,401–407.

Kamei J, Mizoguchi H, Narita M, Tseng LF. Thera-peutic potential of PKC inhibitors in painful dia-betic neuropathy. Expert Opin Investig Drugs. 2011, 10, 1653–64.

Jain D, Bansal MK, Dalvi R, Upaganlawar A, Somani R. Protective effect of diosmin against dia-betic neuropathy in experimental rats. J Int Med. 2004, 12(1),35-41.

Patil MK, Kandhare AD, Bhise SD. Anti-inflammatory effect of Daucus carota root on ex-perimental colitis in rats. Int J Phar Pharmaceutical Sci. 2012, 4(1), 337–43.

Upaganlawar A, Balaraman R. Protective effects of Pomegranates fruit juice on electrocardiographic, biochemical and Histoarchitectural changes in iso-proterenol induced myocardial infarction in rats. J Int Health Sci. 2013, 1(1), 20-27.

Dixon IMC, Kaneko M, Hata T, Panagia V, Dhalla NS. Alteration in cardiac membrane Ca2+ transport during oxidative stress. Mol Cell Bio-chem. 1990, 99,125-133.

Kim SY, Lee JH, Yang ES, Kil IS, Park JW. Human sensitive to apoptosis gene protein inhibits perox-ynitrite-induced DNA damage. Biochem Biophy Res Commun. 2008, 301 (3), 671-674.

Miura T, Ueda N, Yamada K, Fukushima M, Ishida T, Kaneko T et al. Antidiabetic effects of corosolic acid in KKAy diabetic mice. Biol Pharm Bull. 2006, 29, 585–587.

Fukushima M, Mastuyama F, Ueda N, Egawa K, Takemoto J, Kajimoto Y, et al. Effect of corosolic acid on post challenge plasma glucose levels. Dia-betes Res Clin Pract. 2006, 73, 174-177.


  • There are currently no refbacks.