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.

Recently, it has been shown that alpha‐synuclein oligomers and neuroinflammation can play an important role in the development of Parkinsons disease, Alzheimer's disease, and dementia. This study, investigated the potential cytoprotective effect of Fisetin and Ibuprofen in rat pheochromocytoma (PC12) cells prior to intoxication with MPP+. Cell viability was measured by MTT assay, and alpha‐synuclein expression was assessed by western blot. PC12 cells were pretreated with varying doses of fisetin for 2 hours prior to treatment with MPP+ for 48 hours and 72 hours. Pretreatment with fisetin produced a dose‐dependent increase in cell viability, and showed a maximal increase in cell viability with 2 μg/mL of fisetin. Furthermore, western blot analysis showed a dose‐dependent decrease in the expression of alpha‐synuclein when PC12 cells were pretreated with fisetin prior to treatment with MPP+ for 48 hours. Ibuprofen at 2 mM also decreased alpha‐synuclein expression in PC 12 cells treated with MPP+. The combination of both drugs showed a synergistic effect in the inhibition of alpha‐synuclein expression. The present study indicates that fisetin may be a promising approach for the treatment of neuroinflammation associated with neurodegeneration. In addition, further investigation of the synergistic effect of ibuprofen may elucidate the underlying mechanisms of the neuroprotection.