Abstract

Several studies mentioned the association of oxidative stress and neuroinflammation with Parkinson's disease (PD). In the MPTP‐injured PC12 cells, a rat model of PD, MPTP induces cell death through complex I inhibition in the mitochondria, increases the production of nitric oxide (NO) and pro‐inflammatory mediators such as IL‐1beta and TNF‐alpha. This study, investigated the mechanisms underlying the neuroprotective effect of two anti‐inflammatory drugs, Fisetin and Ibuprofen in MPTP‐induced PC12. Cell viability was measured by MTT assay, IL‐1beta levels were quantified by ELISA, TNF‐alpha expression was assessed by western blot, and NO levels were also evaluated. PC12 cells were pretreated with varying doses of fisetin, ibuprofen, or both drugs in combination for 2 hours, prior to MPTP treatment. Pretreatment with fisetin produced a dose‐dependent increase in cell viability, and a dose‐dependent decrease in the expression of TNF‐alpha. Ibuprofen at 2 μg/ml also decreased TNF‐alpha expression in MPTP treated PC12 cells. The combination of both drugs showed a synergistic effect in the inhibition of TNF‐alpha expression. Fisetin also suppressed the production of NO and IL‐1beta in a dose‐dependent manner, and that both drugs combined showed a synergistic effect in suppressing the NO and IL‐1beta production. The present study indicates that fisetin and ibuprofen may provide a promising approach for the treatment of neuroinflammation associated with PD.

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