Molecular mechanisms of fresh Panax ginseng in treating myocardial ischemia based on FoxO signaling pathway.
10.19540/j.cnki.cjcmm.20240725.301
- Author:
Yu-Xin ZHU
1
;
Yun-Peng QI
1
;
Jie YANG
2
;
Min LUO
2
;
Yi-Xuan SUN
1
;
Si-Yuan LI
1
;
Wen-Juan XU
1
;
Ling DONG
1
Author Information
1. School of Life Sciences, Beijing University of Chinese Medicine Beijing 100029, China.
2. School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 100029, China.
- Publication Type:Journal Article
- Keywords:
FoxO signaling pathway;
fresh Panax ginseng;
molecular mechanisms;
myocardial ischemia;
network pharmacology
- MeSH:
Panax/chemistry*;
Animals;
Mice;
Signal Transduction/drug effects*;
Drugs, Chinese Herbal/administration & dosage*;
Myocardial Ischemia/genetics*;
Male;
Forkhead Transcription Factors/metabolism*;
Humans;
Apoptosis/drug effects*;
Oxidative Stress/drug effects*
- From:
China Journal of Chinese Materia Medica
2024;49(21):5877-5887
- CountryChina
- Language:Chinese
-
Abstract:
Based on the differences in the protective effects of fresh Panax ginseng and its processed products on myocardial ischemia in mice, this study identified the advantageous aspects of fresh P. ginseng. By using network pharmacology combined with cell model validation, the molecular mechanisms of fresh P. ginseng in regulating the FoxO signaling pathway were preliminarily revealed. A mouse model of myocardial ischemia was established via intraperitoneal injection of isoproterenol hydrochloride(ISO). The comparison of the protective effects of fresh P. ginseng and its processed products on myocardial ischemia indicated that fresh P. ginseng had a more pronounced effect in reducing lipid peroxidation and alleviating myocardial ischemia in mice. On this basis, network pharmacology research was conducted, showing that fresh P. ginseng contained 19 dominant active ingredients and 38 key targets, including albumin(ALB), serine/threonine protein kinase(AKT1), epidermal growth factor receptor(EGFR), extracellular signal-regulated kinases(ERK1/2), and mitogen-activated protein kinase(P38). Fresh P. ginseng could regulate various biological functions such as cell proliferation, apoptosis, inflammation, and oxidative stress through signaling pathways including Ras, FoxO, IL-17, and Rap1, thereby protecting cardiomyocytes. Among them, the FoxO signaling pathway was identified as a characteristic pathway for fresh P. ginseng. It was further discovered that the dominant active components of fresh P. ginseng, such as ginsenoside Re, ginsenoside Rg_1, and β-elemene, could regulate this pathway through targets such as AKT, JNK, EGFR, and P38. Biological validation results showed that ginsenoside Re, ginsenoside Rg_1, and β-elemene could enhance cell viability, reduce lactate dehydrogenase(LDH) content, and decrease reactive oxygen species(ROS) levels in the cell supernatant. Target validation results indicated that ginsenoside Rg_1 and β-elemene significantly down-regulated the expression of EGFR protein in the FoxO signaling pathway, while ginsenoside Re and β-elemene significantly down-regulated the expression of ERK1/2 and P38 proteins. This study revealed the advantageous mechanisms of fresh P. ginseng in protecting against myocardial ischemia, providing a theoretical basis for the further development of fresh P. ginseng and related products.
