Curcumin and ferulic acid activate PPARγ-PGC1α signaling and improve mitochondrial function in a 6-OHDA-induced Parkinson's cellular model.

Parkinson’s disease (PD) involves mitochondrial dysfunction and oxidative stress. Curcumin (CUR) and ferulic acid (FA) are phenolic compounds with neuroprotective effects, but their roles in improving mitochondrial function in PD remain poorly understood. This study explores the neuroprotective effects of FA and CUR on mitochondrial function via peroxisome proliferator-activated receptor gamma (PPARγ)-peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) signaling in SHSY5Y cells exposed to 6-hydroxydopamine (6-OHDA). A PD model was created using 6-OHDA (100 µM) in SH-SY5Y cells. Cells were pretreated with CUR (10 µM) or FA (200 µM) for 24 h, then exposed to 6-OHDA for another 24 h. Cell viability was measured using the MTT assay; apoptosis/necrosis was evaluated with acridine orange-ethidium bromide (AO-EB) staining; oxidative stress was assessed using reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays; and RT-qPCR analyzed PPARγ and PGC1α mRNA expression. CUR and FA improved cell viability, lowered ROS levels, decreased MDA levels, preserved GSH levels, reduced apoptosis and necrosis, and increased PPARγ and PGC1α mRNA expression compared with 6-OHDA alone. These findings suggest that CUR and FA activate the PPARγ–PGC1α signaling pathway, a key regulator of mitochondrial biogenesis, and are associated with reduced oxidative stress and cell death, highlighting their potential as a therapeutic approach for PD.