Carnosic Acid Attenuated the Motor Impairment by Bisphenol A is Related to the Regulation of Autophagy Through Parkin in In Vitro and In Vivo.

Bisphenol A (BPA) is an endocrine-disrupting compound linked to impairments in motor function and the manifestation of anxiety-like behaviors. The present study investigated the effects of carnosic acid (CA) on BPA-induced motor deficits and explored the role of parkin in the autophagic mechanism. First, C57BL/6 J male mice were orally administered with CA (5 mg/kg and 20 mg/kg) or RE (80 mg/kg rosemary extract) to test the motor function and anxiety-like behaviors in BPA (50 μg/kg) treatment. The results showed that CA and RE ameliorate BPA-induced motor impairments and anxiety-like behaviors. Moreover, CA and RE attenuated BPA-induced phosphorylation of tau and α-synuclein while restoring the expression levels of autophagy-related proteins, including parkin, PINK1, PI3K, Atg7, Beclin1, and LC3B-II. Then, SH-SY5Y cells were treated with 20 nM BPA and 1 μM CA or 0.5 μg/mL RE for 18 h. The results showed that treatment of CA and RE with BPA activated the parkin pathway and reduced the levels of p-tau and p-α-synuclein. Moreover, treatment of CA or RE with BPA restored the parkin signaling, resulting in the upregulation of autophagy-related proteins. However, wortmannin treatment attenuated this restorative effect of CA or RE. Additionally, transfection with parkin siRNA in cells reversed the ability of CA or RE to counteract BPA-induced reductions in autophagy-related proteins and increased the accumulation of misfolded proteins. Therefore, the results indicated that CA and RE improved motor impairments and reduced the accumulation of misfolding proteins induced by BPA, potentially through regulating autophagy by parkin.