Aim: Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA-induced excitotoxic cell death in rats. Material and Methods: QA was administered intrastriatally at a dose of 200 nmol/2 µl saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1β, IL-6 and TNF-α) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4-dihydroxyphenylacetic acid and homovanillic acid) estimation. Results: CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone. Conclusion: This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats.

Leipnitz G, Schumacher C, Scussiato K, Dalcin KB, Wannmacher CM, Wyse AT, Dutra-Filho CS, Wajner M, Latini A: Quinolinic acid reduces the antioxidant defenses in cerebral cortex of young rats. Int J Dev Neurosci 2005;23:695-701.
Kalonia H, Kumar P, Kumar A, Nehru B: Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats. Inflammopharmacology 2009;17:211-219.
Kumar P, Kalonia H, Kumar A: Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity. Eur J Pharmacol 2012;674:265-274.
He S, Bausch SB: Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis. Neuropharmacology 2014;77:379-386.
Acuña AI, Esparza M, Kramm C, Beltrán FA, Parra AV, Cepeda C, Toro CA, Vidal RL, Hetz C, Concha II, Brauchi S, Levine MS, Castro MA: A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice. Nat Commun 2013;4:2917.
Tapia E, Soto V, Ortiz-Vega KM, Zarco-Márquez G, Molina-Jijón E, Cristóbal-García M, Santamaría J, García-Niño WR, Correa F, Zazueta C, Pedraza-Chaverri J: Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats. Oxid Med Cell Longev 2012;2012:269039.
Phom L, Achumi B, Alone DP, Muralidhara, Yenisetti SC: Curcumin's neuroprotective efficacy in Drosophila model of idiopathic Parkinson's disease is phase specific: implication of its therapeutic effectiveness. Rejuvenation Res 2014;17:481-489.
Ravichandran R: Pharmacokinetic study of nanoparticulate curcumin: oral formulation for enhanced bioavailability. J Biomater Nanobiotechnol 2013;4:291-299.
Henrotin Y, Priem F, Mobasheri A: Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Springerplus 2013;2:56.
Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N: Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res 2011;55:1169-1176.
Feng Q, Ma Y, Mu S, Wu J, Chen S, Ouyang L, Lei W: Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats. PLoS One 2014;9:e91512.
Kandasamy M, Reilmann R, Winkler J, Bogdahn U, Aigner L: Transforming growth factor-beta signaling in the neural stem cell niche: a therapeutic target for Huntington's disease. Neurol Res Int 2011;2011:124256.
Dodda D, Chhajed R, Mishra J, Padhy M: Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: role of quercetin. Indian J Pharmacol 2014;46:286-291.
Kalonia H, Mishra J, Kumar A: Targeting neuro-inflammatory cytokines and oxidative stress by minocycline attenuates quinolinic-acid-induced Huntington's disease-like symptoms in rats. Neurotox Res 2012;22:310-320.
Bishnoi M, Chopra K, Rongzhu L, Kulkarni SK: Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence. Neurotox Res 2011;20:215-225.
Reilmann R: Pharmacological treatment of chorea in Huntington's disease-good clinical practice versus evidence-based guideline. Mov Disord 2013;28:1030-1033.
Chen JF, Sonsalla PK, Pedata F, Melani A, Domenici MR, Popoli P, Geiger J, Lopes LV, de Mendonça A: Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and ‘fine tuning' modulation. Prog Neurobiol 2007;83:310-331.
Subhashini, Chauhan PS, Kumari S, Kumar JP, Chawla R, Dash D, Singh M, Singh R: Intranasal curcumin and its evaluation in murine model of asthma. Int Immunopharmacol 2013;17:733-743.
Kulkarni SK, Bhutani MK, Bishnoi M: Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology (Berl) 2008;201:435-442.
Rinwa P, Kumar A, Garg S: Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression. PLoS One 2013;8:e61052.
Prasad S, Tyagi AK, Aggarwal BB: Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat 2014;46:2-18.
Thangarajan S, Deivasigamani A, Natarajan SS, Krishnan P, Mohanan SK: Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum. Int J Neurosci 2014;124:673-684.
Thonda VSSS, Suddhasatwa B, Handral M: Neuroprotective evaluation of ethanolic leaf extracts of dalbergia sissoo in monosodium glutamate induced neurotoxicity in rats. Int J Pharm Sci Res 2014;5:829-838.
Wills ED: Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966;99:667-676.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR: Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982;126:131-138.
Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-77.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J biol Chem 1951;193:265-275.
Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL: The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci U S A 2005;102:5588-5593.
Lasley SM, Gilbert ME: Rat hippocampal glutamate and GABA release exhibit biphasic effects as a function of chronic lead exposure level. Toxicol Sci 2002;66:139-147.
Wang L, Maher TJ, Wurtman RJ: Oral L-glutamine increases GABA levels in striatal tissue and extracellular fluid. FASEB J 2007;21:1227-1232.
Akula KK, Kaur M, Bishnoi M, Kulkarni SK: Development and validation of an RP-HPLC method for the estimation of adenosine and related purines in brain tissues of rats. J Sep Sci 2008;31:3139-3147.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.