Garcinia xanthochymus extract protects PC12 cells from H2O2-induced apoptosis through modulation of PI3K/AKT and NRF2/HO-1 pathways

The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit Et OAc fraction(fruit-EFr., 12.5–50 μmol·L) of G. xanthochymus for 24 h prior to HOexposure markedly improved cell viability and increased the activities of antioxidant enzymes(superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases(MMP), and scavenged reactive oxygen species(ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3 K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3 K/AKT pathway and that it could suppress HO-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling pathways.