Garcinia xanthochymus extract protects PC12 cells from HO-induced apoptosis through modulation of PI3K/AKT and NRF2/HO-1 pathways.
10.1016/S1875-5364(18)30016-5
- Author:
Jing XU
1
;
Sheng GAN
1
;
Jun LI
1
;
De-Bing WAND
1
;
Yu CHEN
2
;
Xin HU
3
;
Guang-Zhong YANG
4
Author Information
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.
3. Laboratory for Natural Products Chemistry, School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address: huxin5540@126.com.
4. Laboratory for Natural Products Chemistry, School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address: yanggz888@126.com.
- Publication Type:Journal Article
- Keywords:
Garcinia xanthochymus;
Nrf2/HO-1 signaling pathways;
Oxidative stress;
PC12;
PI3K/Akt pathway
- MeSH:
Animals;
Antioxidants;
metabolism;
pharmacology;
Apoptosis;
drug effects;
Biological Transport;
Cell Survival;
Cytochromes c;
metabolism;
Fruit;
Garcinia;
Heme Oxygenase-1;
metabolism;
Hydrogen Peroxide;
NF-E2-Related Factor 2;
metabolism;
Oxidative Stress;
drug effects;
PC12 Cells;
Phosphatidylinositol 3-Kinase;
metabolism;
Phosphatidylinositol 3-Kinases;
Phosphorylation;
Plant Extracts;
pharmacology;
Protective Agents;
pharmacology;
Proto-Oncogene Proteins c-akt;
metabolism;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Rats;
Signal Transduction;
bcl-2-Associated X Protein;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(11):825-833
- CountryChina
- Language:English
-
Abstract:
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 HO-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc fraction (fruit-EFr., 12.5-50 µmol·L) of G. xanthochymus for 24 h prior to HO 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 PI3K. 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 PI3K/AKT pathway and that it could suppress HO-induced oxidative damage via PI3K/AKT and NRF2/HO-1 signaling pathways.
