Berberine protects hepatocyte from hypoxia/reoxygenation-induced injury through inhibiting circDNTTIP2.

Abstract

During hepatic ischemia-reperfusion injury, the excessive release of inflammatory cytokines can activate the intracellular signal transduction cascade to induce hepatocyte injury. Apoptosis is an important way of cell death after I/R injury. Berberine, a common quaternary ammonium alkaloid, has anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects. An increasing number of studies have revealed the importance of non-coding RNAs, including microRNA, long non-coding RNAs and circular RNAs (circRNAs), as regulators of the effects of berberine. In this study, we investigated the mechanism of berberine against liver ischemia-reperfusion injury in vitro. In this study, hypoxia-reoxygenation (H/R)-treated L02 cells were pretreated with berberine to study the role and mechanism of berberine in resisting hepatic ischemia-reperfusion injury. The results show that berberine pre-treatment increased the cell viability of H/R-challenged cells, reduced H/R-induced apoptosis and ROS production, reversed H/R-increased on IL-6, IL-1β, TNF-α, and H/R-decreased IL-10 expression. Mechanically, berberine protect hepatocyte from H/R injury, at least partially, through circDNTTIP2. In addition, circDNTTIP2 can bind to the TATA box of caspase3 promoter, thereby promoting caspase 3-related cell apoptosis and the release of inflammatory cytokines. This study found that berberine has a protective effect on H/R-induced hepatocyte damage by inhibiting a novel circRNA, circDNTTIP2. This study provides potential treatment strategies and treatment targets for liver ischemia-reperfusion injury.