1. 5(S)-5-Carboxystrictosidine from the Root of Mappianthus iodoides Ameliorates H2 O2 -induced Apoptosis in H9c2 Cardiomyocytes via PI3K/AKT and ERK Pathways.
- Author
-
Han, Ying, Xi, Junli, Zhang, Puzhao, Gong, Ming, Luo, Tao, Shao, Feng, Li, Yongxin, Zhong, Lingyun, and Quan, Hexiu
- Subjects
- *
CHINESE medicine , *SUPEROXIDE dismutase , *FLOW cytometry , *ALKALOIDS , *APOPTOSIS , *PLANT roots , *CELLULAR signal transduction , *OXIDATIVE stress , *LACTATE dehydrogenase , *CATALASE , *DESCRIPTIVE statistics , *MEDICINAL plants , *MYOCARDIUM , *HYDROGEN peroxide , *CELL death , *MOLECULAR structure , *WESTERN immunoblotting , *PHOSPHOTRANSFERASES , *CELL survival , *HEART cells , *MALONDIALDEHYDE , *CASPASES - Abstract
5(S)-5-carboxystrictosidine (5-CS) is a compound found in the root of Mappianthus iodoides , a traditional Chinese medicine used for the treatment of coronary artery disease. The aim of the present study was to investigate the protective effect of 5-CS against oxidative stress-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms. 5-CS pretreatment significantly protected against H2 O2-induced cell death, LDH leakage, and malondialdehyde (MDA) production, which are indicators for oxidative stress injury. 5-CS also enhanced the activity of SOD and CAT. In addition, 5-CS pretreatment significantly inhibited H2 O2-induced apoptosis, as determined by flow cytometer, suppressed the activity of caspase-3 and caspase-9, and attenuated the activation of cleaved caspase-3 and caspase-9. 5-CS also increased Akt and ERK activation altered by H2 O2 using Western blot analysis. The PI3K-specific inhibitor LY294002 abolished 5-CS-induced Akt activation. The ERK-specific inhibitor PD98059 abolished 5-CS-induced ERK activation. Both LY294002 and PD98059 attenuated the protective effect of 5-CS on H9c2 cardiomyocytes against H2 O2-induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H2 O2-induced oxidative stress injury in H9c2 cells by enhancing the activity of the endogenous antioxidant enzymes, inhibiting apoptosis, and modulating PI3K/Akt and ERK signaling pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF