Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K-AKT-mTOR pathway in osteoarthritic chondrocytes

Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various anti-inflammatory, anti-oxidant and anti-aging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)-alpha-induced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgery-induced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagy-related proteins and the anti-apoptotic protein Bcl-2 were significantly increased in PNS-treated OA chondrocytes, but the expression levels of Bax and caspase-3 were decreased; these effects were concentration-dependent. TNF-alpha significantly increased the expression of p-PI3K/p-AKT/p-mTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3K-AKT-mTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)-3 and MMP-13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3K-AKT pathway, thus delaying the degradation of articular cartilage.