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 Baicalin mitigates H9c2 cell viability loss and apoptosis aroused by hypoxia; Baicalin activates HIF1a/BNIP3 pathway in hypoxia-exposed H9c2 cells; Silencing HIF1α weakens the influences of baicalin on hypoxia-exposed H9c2 cells; Baicalin promotes Nrf2/HO-1 pathway in hypoxia-exposed H9c2 cells; Promotion of Nrf2/HO-1 pathway is related to the up-regulation of HIF1α.

• Authors: Hailiang Yu, Bin Chen, Qi Ren
• Journal: Artificial cells, nanomedicine, and biotechnology (Artif Cells Nanomed Biotechnol) Vol. 47 Issue 1 Pg. 3657-3663 (Dec 2019) ISSN: 2169-141X [Electronic] England
• PMID: 31478766 (Publication Type: Journal Article)

Chemical References

• BNIP3 protein, rat
• Flavonoids
• Hypoxia-Inducible Factor 1, alpha Subunit
• Membrane Proteins
• Mitochondrial Proteins
• NF-E2-Related Factor 2
• baicalin
• Heme Oxygenase-1

Topics

• Animals
• Apoptosis (drug effects)
• Cell Hypoxia (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Flavonoids (pharmacology)
• Gene Silencing
• Heme Oxygenase-1 (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (deficiency, genetics, metabolism)
• Membrane Proteins (metabolism)
• Mitochondrial Proteins (metabolism)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Rats
• Signal Transduction (drug effects)