Perillyl alcohol promotes autophagy by suppressing the PI3K-AKT-mTOR signalling pathway in osteoarthritic chondrocytes in vitro.

Osteoarthritis (OA) is a common degenerative disease characterized by chondrocyte death and extracellular matrix (ECM) degradation, but the present OA treatments are only symptomatic and not aetiologic. Autophagy is a key protective mechanism for OA through the inhibition of chondrocyte apoptosis and degeneration. Perillyl alcohol (POH) is a monomer derived from Chinese herbal medicines that can regulate autophagy and has anti-inflammatory effects. In this study, cell viability, chondrocyte phenotype and the expression of molecules involved in autophagy and the PI3K-AKT-mTOR signalling pathway were detected to explore the hypothesis that POH may decrease the progression of OA by regulating autophagy. We found that POH significantly inhibited the expression of inflammatory cytokines, maintained the chondrocyte phenotype, and protected against ECM degeneration. We also provide evidence that the anti-inflammatory effect of POH works by regulating autophagy via the PI3K-AKT-mTOR signalling pathway. This study demonstrates for the first time that POH has a therapeutic effect on arthritis, which suggests that POH may be a promising candidate for OA therapy.