Isoliquiritigenin alleviates energy metabolism imbalance in type 2 diabetic mice / 药学学报

ABSTRACT

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.