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DOI: 10.1055/a-2341-6175
5(S)-5-Carboxystrictosidine from the Root of Mappianthus iodoides Ameliorates H2O2-induced Apoptosis in H9c2 Cardiomyocytes via PI3K/AKT and ERK Pathways
Supported by: Top Discipline of Jiangxi Province,Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine zxyylxk20220103Supported by: The Graduate Student Innovation special Fund Project of Jiangxi Province YC2021-S485
Supported by: Inherited and Innovative Group of Processing Technique of Traditional Chinese Medicine CXTD22003
Supported by: Science and Technology Project of Jiangxi Provincial Health Commission 202211410
Supported by: The Science and Technology Research Project of Jiangxi Provincial Department of Education, China GJJ2200958
Supported by: The Science and Technology Research Project of Jiangxi Provincial Department of Education, China GJJ211204
Supported by: Innovation and Entrepreneurship training program for college students in Jiangxi Province X202310412181
Supported by: Science and technology project of Jiangxi Provincial Administration of Traditional Chinese Medicine 2023B1182
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 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.
Keywords
5(S)-5-carboxystrictosidine - Mappianthus iodoides - Icacinaceae - myocardial apoptosis - reactive oxygen species - PI3K/Akt - ERKSupporting Information
- Supporting Information
The extraction method of 5-CS from Mappianthus iodoides and the effects used in the Western blotting assay are described in the supplemental material.
Publication History
Received: 14 November 2023
Accepted after revision: 10 June 2024
Accepted Manuscript online:
10 June 2024
Article published online:
19 July 2024
© 2024. Thieme. All rights reserved.
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