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Ginsenoside Rh4 prevents endothelial dysfunction as a novel AMPK activator
Jiawei Zhang1, Weiqiang Lv1, Xuyun Liu1
1Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
British Journal of Pharmacology
|May 17, 2024
Summary
Ginsenoside Rh4 activates AMP-activated protein kinase (AMPK) to protect against hyperlipidaemia-induced endothelial dysfunction. This AMPK activator shows promise for treating cardiovascular diseases linked to endothelial injury.
Area of Science:
- Cardiovascular Pharmacology
- Endothelial Biology
- Mitochondrial Medicine
Background:
- AMP-activated protein kinase (AMPK) signaling is a key target for cardiovascular diseases (CVD).
- Mechanisms of AMPK in hyperlipidaemia-induced endothelial dysfunction are not fully understood.
- Novel AMPK activators are needed for effective intervention.
Purpose of the Study:
- Identify a potent AMPK activator for endothelial dysfunction.
- Investigate the efficacy and mechanism of the identified activator against hyperlipidaemia-induced endothelial dysfunction.
Main Methods:
- Screened rare ginsenosides for AMPK activation using molecular docking.
- Induced hyperlipidaemia in mice using poloxamer 407 (P407).
- Induced lipid toxicity in human aortic endothelial cells (HAECs) using palmitic acid (PA).
Main Results:
- Ginsenoside Rh4 demonstrated strong binding to AMPKα1 and activated AMPK.
- Rh4 attenuated endothelial injury and oxidative stress in vivo and in vitro.
- Rh4 restored cell viability, mitochondrial function, and modulated AKT/eNOS, PGC-1α, and P38 MAPK/NFκB pathways.
- Effects of Rh4 were confirmed to be AMPK-dependent.
Conclusions:
- Ginsenoside Rh4 is a novel AMPK activator with protective effects against hyperlipidaemia-induced endothelial dysfunction.
- Rh4 offers potential for preventing and treating endothelial injury-associated CVD.
- This study provides new mechanistic insights into AMPK-targeted therapies for CVD.
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