Neuropharmacological Study on Capsaicin in Scopolamine-injected Mice

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Abstract

Aim: To evaluate the potential beneficial role of Capsaicin in cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice.

Background: Capsaicin is the chief phenolic component present in red chili and is responsible for its pungent and spicy flavor. It affects TRPV1 channels in nociceptive sensory neurons and is present in the hippocampus, and hypothalamus of the brains of rodents and humans.

Objective: The main objective is to investigate the effective role of capsaicin in attenuating cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice and examine the feasible mechanisms.

Methods: Various doses of capsaicin (5, 10, and 20 mg/kg) were given orally to mice daily for 7 consecutive days after the administration of scopolamine. Various behavioral tests (motor coordination, locomotor counts, hole board test) and biochemical assay (Pro-inflammatory cytokines, catalase, lipid peroxidation, nitrite, reduced glutathione, and superoxide dismutase), mitochondrial complex (I, II, III, and IV) enzyme activities, and mitochondrial permeability transition were evaluated in the distinct regions of the brain.

Results: Scopolamine-treated mice showed a considerable reduction in the entries and duration in the light zone as well as in open arms of the elevated plus maze. Interestingly, capsaicin at different doses reversed the anxiety, depressive-like behaviors, and learning and memory impairment effects of scopolamine. Scopolamine-administered mice demonstrated substantially increased pro-inflammatory cytokines levels, impaired mitochondrial enzyme complex activities, and increased oxidative damage compared to the normal control group. Capsaicin treatment reinstated the reduced lipid peroxidation, nitric oxide, catalase, superoxide dismutase, reduced glutathione activity, decreasing pro-inflammatory cytokines and restoring mitochondrial complex enzyme activities (I, II, III, and IV) as well as mitochondrial permeability. Moreover, the IL-1β level was restored at a dose of capsaicin (10 and 20 mg/kg) only. Capsaicin reduced the scopolamine-induced acetylcholinesterase activity, thereby raising the acetylcholine concentration in the hippocampal tissues of mice. Preservation of neuronal cell morphology was also confirmed by capsaicin in histological studies. From the above experimental results, capsaicin at a dose of 10 mg/kg, p.o. for seven consecutive days was found to be the most effective dose.

Conclusion: The experiential neuroprotective effect of capsaicin through the restoration of mitochondrial functions, antioxidant effects, and modulation of pro-inflammatory cytokines makes it a promising candidate for further drug development through clinical setup.

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