Neuroprotective Effects of P-Coumaric Acid on Haloperidol-Induced Catalepsy Through Ameliorating Oxidative Stress and Brain Dopamine Level

Abstract

Objective To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Methods To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson’s disease and adjuvant therapy with antipsychotic drugs.

Chamuangone-enriched rice bran oil ameliorates neurodegeneration in haloperidol-induced Parkinsonian rat model via modulation of neuro-inflammatory mediators and suppression of oxidative stress markers

“…The oxidation of haloperidol by itself or by oxidase results in a considerable amount of oxyradicals and a toxic metabolite that resembles pyridinium and attacks the complex 1 process. Neuroleptics that block D2 receptors in the nigrostriatal neurons of the brain over time cause an increase in basal ganglia dopamine turnover, which may lead to an abundance of free radicals, such as hydrogen peroxide and dopamine quinone, via monoamine oxidase activity (Pathan et al, 2022).…”

Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson’s Disease

“…A polyphenolic compound, para-coumaric acid (p-CA), is a plant-derived secondary metabolite. p-CA is a dietary polyphenol distributed in several natural food sources, such as tomato, carrot, green pepper, and strawberry, functioning majorly as an antioxidant [134,135].…”