Berberine Protects Against Simulated Ischemia/Reperfusion Injury-Induced H9C2 Cardiomyocytes Apoptosis In Vitro and Myocardial Ischemia/Reperfusion-Induced Apoptosis In Vivo by Regulating the Mitophagy-Mediated HIF-1α/BNIP3 Pathway

Abstract

Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (DYm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1a to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1a/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.

Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

“…Recently, berberine extract or pure compound has gained much attention in the newly published research and is among the top pharmaceutical supplements on shelves [412]. The preclinical evidence from huge studies reveals the capability of berberine to treat many diseases [411,[413][414][415][416][417][418][419]. Thus, berberine is clinically studied for many diseases, such as diabetes [410,[420][421][422][423].…”

Ginsenoside Re Treatment Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting HIF-1α Ubiquitination

“…BNIP3, which is a pro-apoptotic protein and a member of Bcl-2 family, is the downstream of HIF-1 signal pathway ( Cai et al, 2017 ). HIF-1α/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury ( Zhu et al, 2020 ). HIF-1α/BNIP3 signaling pathway will be explored in our next study.…”

HIF‑1α in myocardial ischemia‑reperfusion injury (Review)

“…Matsushima et al ( 21 ) demonstrated that HIF-1α may protect cardiac fibroblasts from apoptosis and represent a potential therapeutic target for heart remodeling following hypoxic injury. Additionally, a number of studies have confirmed that HIF-1α prevents MIRI and has a cardioprotective effect ( 22 , 23 ).…”