Beneficial role of capsaicin through modulation of mitochondrial functions in MPTP-injected mice

Capsaicin is one of the major phenolic components present in red chili and is responsible for its aromatic and spicy flavor. Capsaicin has an agonistic effect on TRPV1 channels and is also reported for a neuroprotective role. The study aims to explore the beneficial effects of capsaicin in preventing mitochondrial dysfunctions and examine the possible mechanisms in MPTP (1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine)-injected mice. Capsaicin (5, 10, and 20 mg/kg) was orally given to the MPTP-injected mice model of PD for seven consecutive days. Behavioral tests parameters (resting tremor score, muscle coordination, locomotor counts, hole board test) were observed and biochemical analysis (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase, nitrite, and cytokines level), mitochondrial complex activities (I, II, III, and IV), and mitochondrial permeability transition tests were performed. MPTP mice demonstrated impaired behavior in behavioral tests, elevated resting tremor, increased oxidative stress and cytokine level, and impaired mitochondrial functions compared to the normal control mice. Capsaicin treatment restored the behavioral parameters studied and modulated anti-oxidant activities, nitric oxide levels, cytokines level, mitochondrial complexes activities, and mitochondrial permeability. Moreover, IL-1β level restored toward normal at capsaicin 20 mg/kg only, whereas, for IL-6 and TNF-α, the effect was shown by capsaicin 10 and 20 mg/kg. Preservation of neuronal morphology by capsaicin was also confirmed by histological studies. The observed beneficial effects of capsaicin through the restoration of mitochondrial functions, antioxidant effects, and modulation of cytokines level make it a promising candidate for further development as a pharmacotherapeutics for neurodegenerative disorders through clinical setup.