Study on the mechanism of Gegen Qinlian Decoction for treating type II diabetes mellitus by integrating network pharmacology and pharmacological evaluation

Gegen Qinlian Decoction (GQD) is a classic traditional Chinese medicine prescription that is widely used to clinically treat diabetes mellitus. It is composed of Pueraria lobata (Willd.) Ohwi (ge gen), Scutellaria baicalensis Georgi (huang qin), Coptidis chinensis Franch. (huang lian), and Glycyrrhiza uralensis Fisch. (gan cao). However, the active ingredients in GQD and their mechanism of action are unclear. In this study, we aimed to verify the efficacy of GQD in improving insulin resistance (IR) in diabetic mice and used network pharmacology to identify potential targets and pathways underlying its mechanism of action. A mouse model of diabetes was created by feeding mice a high-fat diet followed by an intraperitoneal injection of streptozotocin. These type II diabetic mice were administered either a clinical dose or a high dose of GQD, after which blood glucose and serum insulin levels were measured to assess its effects on IR. Network pharmacology was used to construct a ‘component-pathway-target’ network to elucidate the likely targets and pathways modulated in common by GQD components. Furthermore, mRNA transcript levels and protein expression levels of oestrogen receptor alpha (ESR1) were determined. The in vivo experiment showed that GQD markedly decreased blood glucose and increased serum insulin levels in type II diabetic mice. Network pharmacology and bioinformatics analysis indicated that GQD regulated 82 corresponding proteins and 59 relevant biological pathways associated with diabetes. One such target was ESR1, which was significantly decreased at both the mRNA and protein levels in diabetic mice, but whose levels were significantly increased by GQD treatment. This project provides a scientific basis for understanding the effectiveness of multi-component, multi-target compound formulas, as well as a new strategy for investigating therapeutic drugs for type II diabetes and other diseases.