Protective Effect of Carnosic Acid Against Paraquat-induced Redox Impairment and Mitochondrial Dysfunction in SH-SY5Y Cells: Role for PI3K/Akt/Nrf2 Pathway

Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinalis and exerts anti-inflammatory, antioxidant, and anticarcinogenic activities in different cell types. It has been reported that CA is able to cause protective effects on experimental models of neurodegeneration. However, the exact mechanism by which CA prevents neuronal degeneration remains to be better studied. We investigated here whether there is a role for CA as a neuroprotective agent in a paraquat (PQ) model of Parkinson's disease (PD) regarding cellular and mitochondrial-related redox parameters. SH-SY5Y cells were treated with CA for 12h and were exposed to 100 μM PQ for 24h. It was found that CA at different concentrations prevented the effects of PQ on cell viability and redox parameters. CA alleviated reactive oxygen and nitrogen species production elicited by PQ, as well as decreased the toxic effect on mitochondrial function. Inhibition of Pi3K/Akt pathway with LY294002 or silencing of Nrf2 expression partially blocked the reversal of redox impairment induced by CA. Therefore, CA activated Nrf2 through modulation of PI3K/Akt pathway resulting in increased levels of antioxidant enzymes and consequent neuroprotection. Thus, CA may be viewed as a potential neuroprotective agent to be used in cases of Parkinson's disease (PD).