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

作　　者：XU Jing GAN Sheng LI Jun WAND De-Bing CHEN Yu HU Xin YANG Guang-Zhong 

机构地区：[1]Laboratory for Natural Products Chemistry, School of Pharmaceutical Sciences, South-Central University for Nationalities,Wuhan 430074, China [2]College of Chemistry and Material Sciences, South Central University for Nationalities, Wuhan 430074, China

出　　处：《Chinese Journal of Natural Medicines》2017年第11期825-833,共9页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.31370379);the National Natural Science Foundation Youth Project Financing(No.81201610);State Ethnic Affairs Commission Research Project(No.CMZY13012);Universities of Hubei Province Outstanding Youth Scientific Innovation Team Plan(No.T201220)

摘　　要：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^(-1)) of G. xanthochymus for 24 h prior to H_2O_2 exposure 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 H_2O_2-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling 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^（-1）） of G. xanthochymus for 24 h prior to H_2O_2 exposure 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 H_2O_2-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling pathways.

关 键 词：GARCINIA xanthochymus Oxidative stress PC12 PI3K/AKT pathway Nrf2/HO-1 signaling PATHWAYS 

分 类 号：R965[医药卫生—药理学]