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5(S)-5-Carboxystrictosidine from the Root of Mappianthus iodoides Ameliorates H2O2-induced Apoptosis in H9c2 Cardiomyocytes via PI3K/AKT and ERK Pathways.
- Source :
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Planta medica [Planta Med] 2024 Sep; Vol. 90 (11), pp. 885-895. Date of Electronic Publication: 2024 Jun 10. - Publication Year :
- 2024
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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 H <subscript>2</subscript> O <subscript>2</subscript> -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 H <subscript>2</subscript> O <subscript>2</subscript> -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 H <subscript>2</subscript> O <subscript>2</subscript> 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 H <subscript>2</subscript> O <subscript>2</subscript> -induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H <subscript>2</subscript> O <subscript>2</subscript> -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.<br />Competing Interests: The authors declare that they have no conflicts of interest.<br /> (Thieme. All rights reserved.)
- Subjects :
- Animals
Rats
MAP Kinase Signaling System drug effects
Cell Line
Signal Transduction drug effects
Caspase 9 metabolism
Myocytes, Cardiac drug effects
Hydrogen Peroxide toxicity
Hydrogen Peroxide pharmacology
Apoptosis drug effects
Proto-Oncogene Proteins c-akt metabolism
Phosphatidylinositol 3-Kinases metabolism
Oxidative Stress drug effects
Plant Roots chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1439-0221
- Volume :
- 90
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Planta medica
- Publication Type :
- Academic Journal
- Accession number :
- 38857860
- Full Text :
- https://doi.org/10.1055/a-2341-6175