Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats

Abstract

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.

Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention

“…It has a direct inhibitory effect on lipid peroxidation 86 . Its bioavailability and effect is further enhanced by the addition of the alkaloid piperine from ( Piper nigrum ), and both exhibit a synergetic effect which results in neuroprotection in an ND rat model 87 . Curcumin has been shown to be neuroprotective and have great potential for the prevention or treatment of neurological disorders like HD and PD 88 .…”

Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?

“…Although Nrf2 signalling is impaired in the presence of mutated huntingtin, pharmacological activators of Nrf2 are protective in animal models of Huntington’s disease ( Table 6 ). Triterpenoids and dimethyl fumarate are protective in genetic models of Huntington’s disease, improving survival and motor function and increasing striatal neuron survival [ 212 , 213 ], and curcumin is effective in multiple models of Huntington’s disease [ 214 , 215 , 216 ]. Dimethyl fumarate, CDDO-methylamide, sulforaphane, curcumin nanoparticles, tert-butylhydroquinone, the citrus flavonone naringin, the ginseng extract protopanaxtriol, the organic disulphide cystamine and AI-3 are all protective against 3-nitropropionic acid and decrease striatal lesion size in rats and mice [ 25 , 70 , 207 , 208 , 209 , 211 , 217 , 218 ].…”

The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes

“…A variety of naturally occurring compounds can stimulate Nrf2 activation, such as curcumin (CUR, 1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-hetadiene-3,5-dione) [17], a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa Linn [18]. There are reports demonstrating the cytoprotective properties of CUR as an antioxidant in several preclinical models of Huntington [19], Alzheimer [20], and Parkinson [21] diseases. CUR acts as both a free radical scavenger (direct antioxidant) [22] and as an Nrf2 inducer (indirect antioxidant) [23], although the mechanism by which CUR activates Nrf2 remains unclear.…”