Baicalin relieves hypoxia-aroused H9c2 cell apoptosis by activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway

Abstract

Background

Myocardial ischemia is the main reason for ischemic heart disease. Baicalin is a plant-derived flavonoid with cardio-protective activity. Herein, we tested the influences of baicalin on cardiomyocytes H9c2 apoptosis aroused by hypoxia stimulation.

Methods

Firstly, H9c2 cells were subjected to hypoxia and/or baicalin exposure. Cell viability and apoptosis, along with hypoxia-inducible factor 1α (HIF1α) and Bcl-2/adenovirus E1B 19-KDa interacting protein 3 (BNIP3) expressions were tested respectively. Then, si-HIF1α was transfected into H9c2 cells to probe whether up-regulation of HIF1α attended to the influences of baicalin on hypoxia-stimulated H9c2 cells. Finally, the regulatory effect of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on HIF1α expression was analyzed.

Results

Hypoxia exposure aroused H9c2 cell viability reduction and apoptosis. Baicalin mitigated H9c2 cell viability reduction and apoptosis aroused by hypoxia. Moreover, HIF1α/BNIP3 pathway was further activated by baicalin in hypoxia-exposed H9c2 cells. Silencing HIF1α lowered the functions of baicalin on hypoxia-exposed H9c2 cells. Besides, baicalin enhanced hypoxia-caused activation of Nrf2/HO-1 pathway. Activation of Nrf2/HO-1 pathway was associated with the up-regulation of HIF1α and protective functions of baicalin on hypoxia-exposed H9c2 cells.

Conclusion

Baicalin relieved cardiomyocytes H9c2 apoptosis aroused by hypoxia might be achieved through activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway.

Highlights

1. Baicalin mitigates H9c2 cell viability loss and apoptosis aroused by hypoxia;

2. Baicalin activates HIF1a/BNIP3 pathway in hypoxia-exposed H9c2 cells;

3. Silencing HIF1α weakens the influences of baicalin on hypoxia-exposed H9c2 cells;

4. Baicalin promotes Nrf2/HO-1 pathway in hypoxia-exposed H9c2 cells;

5. Promotion of Nrf2/HO-1 pathway is related to the up-regulation of HIF1α.

Keywords:

• Myocardial ischemia
• cardiomyocytes damage
• baicalin
• hypoxia
• hypoxia-inducible factor 1α
• Nrf2/HO-1 pathway

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Expression of Concern

Disclosure statement

No potential conflict of interest was reported by the authors.