Carnosic acid attenuates inflammation, oxidative stress and mitochondrial dysfunction in neurons via activation of AMPK/SIRT1 pathway

Abstract

Purpose: To determine the effects and mechanism of action of carnosic acid (CA), a natural diterpenoid compound, on the neuroprotective roles of anesthetics. Methods: The effects of carnosic acid (CA) on cell viability and apoptosis were evaluated by MTT assay and flow cytometry, respectively. Its effects on mitochondrial damage was assessed by JC-1 staining, while oxidative stress and inflammatory response were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot assays, respectively. Immunoblot assays were performed to evaluate the effect of CA on AMPK/SIRT1 pathway. Results: Carnosic acid (CA) increased the survival rate of isoflurane-induced neuronal cells, but inhibited isoflurane-induced mitochondrial damage in neurons (p < 0.01). CA also suppressed isoflurane-induced oxidative stress in neurons, and inhibited isoflurane-induced neuronal inflammatory response (p < 0.01). Furthermore, CA activated AMPK/SIRT1 pathway, and also attenuated inflammation, oxidative stress and mitochondrial dysfunction in neurons induced by isoflurane (p < 0.01). Conclusion: Carnosic acid attenuates inflammation, oxidative stress and mitochondrial dysfunction in neurons via activation of AMPK/SIRT1 pathway. Thus, it has potentials for use in the treatment of neurotoxicity