Neuroprotective Effect of Quercetin in Combination with Piperine Against Rotenone- and Iron Supplement–Induced Parkinson’s Disease in Experimental Rats

Parkinson’s disease (PD) is a neurodegenerative disorder caused by selective dopaminergic neuronal loss. Rotenone is a neurotoxin that selectively destroys dopaminergic neurons, leading to PD-like symptoms. Quercetin possesses antioxidant, anti-inflammatory, and neuroprotective properties but a major drawback is its low bioavailability. Therefore, the present study was designed to evaluate the neuroprotective effect of quercetin in combination with piperine against rotenone- and iron supplement–induced model of PD. Rotenone was administered at a dose of 1.5 mg/kg through an intraperitoneal route with iron supplement at a dose of 120 μg/g in diet from day 1 to day 28. Pre-treatment with quercetin (25 and 50 mg/kg, p.o.), piperine (2.5 mg/kg, p.o.) alone, quercetin (25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg), and ropinirole (0.5 mg/kg, i.p.) was administered for 28 days 1 h prior to rotenone and iron supplement administration. All behavioral parameters were assessed on weekly basis. On the 29th day, all animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite, GSH, mitochondrial complexes I and IV), neuroinflammatory (TNF-α, IL-1β, and IL-6), and neurotransmitter (dopamine, norepinephrine, serotonin, GABA, glutamate) estimation. Quercetin treatment attenuated rotenone- and iron supplement–induced motor deficits and biochemical and neurotransmitter alterations in experimental rats. However, combination of quercetin (25 mg/kg) with piperine (2.5 mg/kg) significantly enhanced its neuroprotective effect as compared with treatment with quercetin alone. The study concluded that combination of quercetin with piperine contributed to superior antioxidant, anti-inflammatory, and neuroprotective effect against rotenone- and iron supplement–induced PD in experimental rats.