COMBINED EFFECT OF AQUEOUS EXTRACT OF CURCUMA LONGA LINN.WITH METFORMIN IN DIABETES INDUCED NEUROPTAHIC PAIN IN RATS

Authors

  • ROMAN ADHIKARI Associate Professor,Krupanidhi College of Pharmacy,Bangalore
  • JYOTHI Y
  • DEEPIKA BORA
  • VAMSEE VEENA A

Abstract

Objectives: A number of studies previously conducted have shown that the progression of severity of diabetic Neuropathy relates the increased oxidative stress due to hyperglycemia describing the probable underlying mechanism as changes in the anti-oxidant enzyme level leading to several vascular and neuronal changes. The present investigation was carried out to observe the combined effect of Aqueous Extract of Curcuma longa Linn.(Curcumin) with Metformin  in delaying of Diabetes induced Neuropathic Pain in Rats.

Methods: The high-fat diet treated male SD rats were induced diabetic by a single intra-peritoneal injection of Streptozocin (35mg/kg). Eddy's Hot Plate and Hot Water Tail Immersion test were the Models used to assess the Neuropathic pain. The high Fat diet treated and Diabetic Rats were treated with Metformin (500mg/kg), Curcumin (300mg/kg) and a combination of low dose of Metformin with Curcumin, followed by the oral glucose tolerance test before and after the treatment on both Normal and Diabetic Rats. After 7 weeks of treatment TBARS, SOD, Catalase and GSH levels were also estimated in the sciatic nerve homogenate of Diabetic Rats and compared with the control followed by a supporting histopathological examination of Sciatic Nerve.

Results: Diabetic Rats treated with Curcuma longa Linn. and Metformin  alone and in combination showed a significant improvement in control of blood glucose level and restoration of anti-oxidant enzyme levels. There was a significant improvement in the hyperalgesia (P<0.001) due to Diabetic Neuropathy and also the reaction time to the nociceptive stimuli in Neuropathic pain models was increased after the treatment.

Key Words:   Antioxidant, Curcumin, Diabetes, Metformin, Neuropathy, Streptozocin

Downloads

Download data is not yet available.

Author Biography

ROMAN ADHIKARI, Associate Professor,Krupanidhi College of Pharmacy,Bangalore

Associate Professor

Department of Pharmacology

References

Hsiao CJ, Cherry DK, Beatty PC, Rechtsteiner EA. National

ambulatory medical care survey: 2007 summary. Natl Health Stat

Report 2010;(27):1-32.

Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global

estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res

Clin Pract 2011;94(3):311-21.

Nicolucci A, Carinci F, Cavaliere D, Scorpiglione N, Belfiglio M,

Labbrozzi D, et al. A meta-analysis of trials on aldose reductase

inhibitors in diabetic peripheral neuropathy. The Italian Study Group.

The St. Vincent Declaration. Diabet Med 1996;13(12):1017-26.

Mizoguchi H, Watanabe C, Yonezawa A, Sakurada S. New therapy for

neuropathic pain. Int Rev Neurobiol 2009;85:249-60.

Jin L, Xue HY, Jin LJ, Li SY, Xu YP. Antioxidant and pancreasprotective

effect

of

aucubin on

rats with streptozotocin-induced

diabetes.

Eur J Pharmacol 2008;582(1-3):162-7.

Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR. Metformin,

sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis

or hypoglycemia: A nested case-control analysis. Diabetes Care

;31(11):2086-91.

Al-Abri SA, Hayashi S, Thoren KL, Olson KR. Metformin overdoseinduced

hypoglycemia

in

the

absence

of

other antidiabetic

drugs.

Clin

Toxicol

(Phila). 2013;51(11):444-7.

Galuppo M, Giacoppo S, Bramanti P, Mazzon E. Use of natural

compounds in the management of diabetic peripheral neuropathy.

Molecules 2014;19(3):2877-95.

Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med

;57(1):1-7.

Kunchandy E, Rao MN. Oxygen radical scavenging activity of

curcumin. Int J Pharm 1990;58:237-40.

Jurenka JS. Anti-inflammatory properties of curcumin, a major

constituent of Curcuma longa: A review of preclinical and clinical

research. Altern Med Rev 2009;14(2):141-53.

Fagerberg SE. Studies on the pathogenesis of diabetic neuropathy.

IV. Angiopathia diabetica vasae nervorum. Acta Med Scand

;159(1):59-62.

Reddy AC, Lokesh BR. Studies on spice principles as antioxidants in

the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell

Biochem 1992;111(1-2):117-24.

Na LX, Zhang YL, Li Y, Liu LY, Li R, Kong T, et al. Curcumin improves

insulin resistance in skeletal muscle of rats. Nutr Metab Cardiovasc Dis

;21(7):526-33.

Kumar NP, Annamalai AR, Thakur RS. Antinociceptive property

of Emblica officinalis Gaertn (Amla) in high-fat diet-fed/low dose

streptozotocin induced diabetic neuropathy in rats. Indian J Exp Biol

;47:737-42.

Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity

in vivo. Endocr Rev 1985 Winter;6(1):45-86.

Ali Hussain HE. Hypoglycemic, hypolipidemic and antioxidant

properties of combination of Curcumin from Curcumin longa,Linn and

partially purified product from Abroma Augusta,Linn. in streptozocin

induced diabetes induced nephropathy. Indian J Clin Biochem

;17(2):33-43.

Pushparaj P, Tan CH, Tan BK. Effects of Aberrhoa bilimbi leaf

extract on blood glucose and lipids in streptozotocin-diabetic rats. J

Ethnopharmacol 2000;72(1-2):69-76.

Elastner EF. Inhibition of nitrite formation from hydroxyl ammonium

chloride. A simple assay for super oxide dismutase. Anal Biochem

;70(2):616-20.

Link EM. The mechanism of pH-dependent hydrogen peroxide

cytotoxicity in vitro. Arch Biochem Biophys 1988;265(2):362-72.

Gelvan D, Saltman P. Different cellular targets for Cu- and Fecatalyzed

oxidation

observed

using a Cu-compatible thiobarbituric

acid

assay.

Biochim Biophys Acta

;1035(3):353-60.

Mahboob M, Rahman MF, Grover P. Serum lipid peroxidation and

antioxidant enzyme levels in male and female diabetic patients.

Singapore Med J 2005;46(7):322-4.

Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive

method for measuring thermal nociception in cutaneous hyperalgesia.

Pain 1988;32(1):77-88.

Wang YX, Bowersox SS, Pettus M, Gao D. Antinociceptive properties

of fenfluramine, a serotonin reuptake inhibitor, in a rat model of

neuropathy. J Pharmacol Exp Ther 1999;291(3):1008-16.

Yagihashi S, Yamagishi S, Wada R. Pathology and pathogenetic

mechanisms of diabetic neuropathy: Correlation with clinical signs and

symptoms. Diabetes Res Clin Pract 2007;77 Suppl 1:S184-9.

Pittenger GL, Malik RA, Burcus N, Boulton AJ, Vinik AI. Specific

fiber deficits in sensorimotor diabetic polyneuropathy correspond to

cytotoxicity against neuroblastoma cells of sera from patients with

diabetes. Diabetes Care 1999;22(11):1839-44.

Andrade P, Visser-Vandewalle V, Del Rosario JS, Daemen MA,

Buurman WA, Steinbusch HW, et al. The thalidomide analgesic effect

is associated with differential TNF-a receptor expression in the dorsal

horn of the spinal cord as studied in a rat model of neuropathic pain.

Brain Res 2012;1450:24-32.

Greene DA, Stevens MJ, Obrosova I, Feldman EL. Glucose-induced

oxidative stress and programmed cell death in diabetic neuropathy. Eur

J Pharmacol 1999 30;375(1-3):217-23.

Jovanovic SV, Steenken S, Borne CW, Simic MG. H-atom transfer

is a preferred anti-oxidant mechanism of curcumin. J Am Chem

Soc1999;121:9677-81.

Spinas GA. The dual role of nitric oxide in islet beta-cells. News

Physiol Sci 1999;14:49-54.

Weber WM, Hunsaker LA, Roybal CN, Bobrovnikova-Marjon EV,

Abcouwer SF, Royer RE, et al. Activation of NFkappaB is inhibited by

curcumin and related enones. Bioorg Med Chem 2006;14(7):2450-61.

Meghana K, Sanjeev G, Ramesh B. Curcumin prevents streptozotocin-

induced islet damage by scavenging free radicals: A prophylactic and

protective role. Eur J Pharmacol 2007;577(1-3):183-91.

Seo KI, Choi MS, Jung UJ, Effect of curcumin supplementation

on blood glucose, plasma insulin, and glucose homeostasis related

enzyme activities in diabetic db/db mice. Mol Nutr Food Res

;52(11):995-1004.

Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, et al.

Beneficial effects of curcumin on hyperlipidemia and insulin resistance

in high-fat-fed hamsters. Metabolism 2008;57(11):1576-83.

Kuhad A, Chopra K. Lycopene ameliorates thermal hyperalgesia

and cold allodynia in STZ-induced diabetic rat. Indian J Exp Biol

;46(2):108-11.

Bridges D, Thompson SW, Rice AS. Mechanisms of neuropathic pain.

Br J Anaesth 2001;87(1):12-26.

Sharma S, Kulkarni SK, Agrewala JN, Chopra K. Curcumin attenuates

thermal hyperalgesia in a diabetic mouse model of neuropathic pain.

Eur J Pharmacol 2006;536(3):256-61.

Published

01-09-2015

How to Cite

ADHIKARI, R., J. Y, D. BORA, and V. VEENA A. “COMBINED EFFECT OF AQUEOUS EXTRACT OF CURCUMA LONGA LINN.WITH METFORMIN IN DIABETES INDUCED NEUROPTAHIC PAIN IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 8, no. 5, Sept. 2015, pp. 166-70, https://journals.innovareacademics.in/index.php/ajpcr/article/view/7137.

Issue

Section

Original Article(s)