Evaluation of fisetin as a potential inducer of mitochondrial biogenesis in SH-SY5Y neuronal cells

Iran J Basic Med Sci. 2023;26(11):1320-1325. doi: 10.22038/IJBMS.2023.72272.15714.

Abstract

Objectives: Increasing evidence implicates impaired mitochondrial biogenesis as an important contributor to mitochondrial dysfunction, which plays a central role in the pathogenesis of neurodegenerative diseases including Parkinson's disease (PD). For this reason, targeting mitochondrial biogenesis may present a promising therapeutic strategy for PD. The present study attempted to investigate the effects of fisetin, a dietary flavonoid, on mitochondrial biogenesis and the expression of PD-associated genes in neuronal cells.

Materials and methods: The effects of fisetin on mitochondrial biogenesis were evaluated by three different approaches; PGC-1α and TFAM mRNA expressions by RT-qPCR, mitochondrial DNA (mtDNA) content by quantitative PCR and mitochondrial mass by MitoTracker staining. Next, a PCR array was performed to evaluate the effects of fisetin on the expression profile of PD-associated genes. Finally, the common targets of fisetin and PD were analyzed by in silico analyses.

Results: The results demonstrated that fisetin treatment can increase PGC-1α and TFAM mRNA levels, mtDNA copy number, and mitochondrial mass in neuronal cells. Fisetin also altered the expressions of some PD-related genes involved in neuroprotection and neuronal differentiation. Moreover, the bioinformatics analyses suggested that the AKT1-GSK3B signaling might be responsible for the potential neuroprotective effects of fisetin.

Conclusion: Collectively, these results imply that fisetin could modulate some neuroprotective mechanisms including mitochondrial biogenesis, and may serve as a potential drug candidate for PD.

Keywords: Fisetin; Mitochondria; PCR; Parkinson’s disease; SH-SY5Y; mtDNA.