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.
Subject(s)
Animals , Rats , Antioxidants , Metabolism , Pharmacology , Apoptosis , Biological Transport , Cell Survival , Cytochromes c , Metabolism , Fruit , Garcinia , Heme Oxygenase-1 , Metabolism , Hydrogen Peroxide , NF-E2-Related Factor 2 , Metabolism , Oxidative Stress , 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 , Signal Transduction , bcl-2-Associated X Protein , MetabolismABSTRACT
Objective: To observe the effects of panaxtriol saponin (PTS) on CK-MB, cTnI, IL-6, TNF-α, and ultrastructure against myocardial ischemia-reperfusion injury (MIRI) in rats. Methods: Wistar rats were randomly divided into six groups: Sham, MIRI model, positive control, and 22.5, 45, and 90 mg/kg PTS groups. Animal MIRI model was made by ligating the left anterior descending coronary artery. Drug was given for seven consecutive days before the operation by ip injection. Rats were sacrificed after 30 min ischemia and 24 h reperfusion. CK-MB, cTnI, IL-6, and TNF-α in serum were measured and the changes of myocardial ultrastructure were observed. Real time PCR was used to evaluate change of NRF2 and HO-1 mRNA level in myocardial tissue. Results: Compared with model, PTS 45 and 90 mg/kg reduced the CK-MB, cTnI, IL-6, and TNF-α in serum and improve the myocardium ultrastructure. Nrf2 and HO-1 mRNA levels in PTS treatment group were higher than those in MIRI model group. Conclusion: PTS plays a crucial role in cardioprotection against the ischemia and reperfusion injury in rats. The protective mechanism suggests that PTS could stimulate NRF2/HO-1 expression in myocardial tissue and then inhibit myocardial inflammation.