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Ginsenoside Rb3 Protects Cardiomyocytes Against hypoxia/reoxygenation Injury via Activating the Antioxidation Signaling Pathway of PERK/Nrf2/HMOX1

Ginsenoside Rb3 Protects Cardiomyocytes Against hypoxia/reoxygenation Injury via Activating the Antioxidation Signaling Pathway of PERK/Nrf2/HMOX1

Jing Sun, Xiaohong Yu, Haiquan Huangpu, Fengzhen Yao

Biomed Pharmacother. 2019 Jan;109:254-261.

PMID: 30396083

Abstract:

Objectives:
This study aimed to investigate the pharmacological function and underlying regulation mechanisms of Ginsenoside-Rb3 (G-Rb3) in cardioprotection.
Methods:
Cultured H9C2 cells were pre-treated with gradient concentrations of G-Rb3, and subsequently challenged with hypoxia/reoxygenation (H/R) treatment. The generation of intracellular reactive oxygen species (ROS) and cellular antioxidatant capacity were quantified. Cell apoptosis was measured by flow cytometry. Myocardial ischemia reperfusion injury (MIRI) rat models constructed by coronary artery ligation surgery were orally administrated with G-Rb3 for 5 consecutive days, and then infarction area, apoptosis ratio and total antioxidant capacity (T-AOC) of myocardial tissues were measured. PERK phosphorylation inhibitor GSK2656157 and Nrf2 translocation inhibitor ML385 were co-treated with G-Rb3 to further verify the signaling pathway mediated by G-Rb3.
Results:
H/R treatment induced prominent ROS deposition and elevated cell apoptosis ratio in H9C2 cells. G-Rb3 pretreatment suppressed intracellular ROS accumulation and enhanced T-AOC, partially rescuing cardiomyocytes from oxidative stress and apoptosis induced by H/R. In vivo, the cardiac infarction area of MIRI model rats was reduced by G-Rb3 treatment via improved total antioxidant levels. In the further functional and mechanistic studies, G-Rb3 was found to induce PERK phosphorylation and nuclear translocation of transcriptional factor Nrf2, promoting the expression of antioxidative genes such as HMOX1. Inhibitors GSK2656157 and ML385 reversed the effects of G-Rb3.
Conclusion:
Our studies revealed a novel mechanism of G-Rb3 to attenuates oxidative stress via activating the antioxidation signaling pathway of PERK/Nrf2/HMOX1 in vivo and in vitro, which may help us to enrich the theoretical knewledge of Ginsenoside-Rb3 in cardiopretection.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP68406268	Ginsenoside Rb3		68406-26-8	Price

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