5(S)-5-Carboxystrictosidine from the Root of Mappianthus iodoides Ameliorates H2O2-induced Apoptosis in H9c2 Cardiomyocytes via PI3K/AKT and ERK Pathways

Author:

Han Ying,Xi Junli1,Zhang Puzhao2,Gong Ming1,Luo Tao3,Shao Feng2,Li Yongxin1,Zhong Lingyun4,Quan Hexiu1

Affiliation:

1. Department of Physiology, College of Chinese Medicine and Life Science, Jiangxi University of Chinese Medicine, Nanchang City, Jiangxi Province, China

2. Key Laboratory of Innovation Drug and Efficient Energy-saving Pharmaceutical Equipment, Jiangxi University of Chinese Medicine, Nanchang City, Jiangxi Province, China

3. Blood Purification Center of the First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China

4. College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang City, Jiangxi Province, China

Abstract

Abstract5(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 H2O2-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 H2O2-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 H2O2 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 H2O2-induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H2O2-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.

Funder

Top Discipline of Jiangxi Province,Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine

The Graduate Student Innovation special Fund Project of Jiangxi Province

Inherited and Innovative Group of Processing Technique of Traditional Chinese Medicine

Science and Technology Project of Jiangxi Provincial Health Commission

The Science and Technology Research Project of Jiangxi Provincial Department of Education, China

Innovation and Entrepreneurship training program for college students in Jiangxi Province

Science and technology project of Jiangxi Provincial Administration of Traditional Chinese Medicine

Publisher

Georg Thieme Verlag KG

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