Study on the Mechanism of Lupenone for Treating type 2 Diabetes by Integrating Pharmacological Evaluation and Network Pharmacology

Abstract Background: Lupenone (LUP) is the active ingredient of Rhizoma Musae, which has good anti-diabetes effects, but the underlying mechanism is unclear. In this study, animal experiments combined with network pharmacology were used to explore the mechanism of LUP for treating diabetes. Methods: Type 2 diabetic rats with insulin resistance (IR) were induced by a high-fat diet and streptozotocin. the fasting blood glucose (FBG), index of oxidative stress, blood lipids, and IR-related targets in skeletal muscle and adipose were detected. a network pharmacology-based strategy was also adopted to clarify the mechanism of LUP for treating diabetes by improving IR. Results: LUP decreased the FBG levels and synthesis of glycogen, improved oxidative stress and lipid metabolism disorders, and increased the gene and protein expression of insulin receptor, insulin receptor substrate (IRS)-1, IRS-2, glucose transporter type 4 (GLUT-4) in skeletal muscle and peroxisome proliferator-activated receptor γ, IRS-1, IRS-2, GLUT-4 in adipose. Network pharmacology analysis revealed that LUP improves IR by multiple targets (like INS, TP53, TNF, SRC and ESR1) and signal pathways. Conclusion: These results suggested that the mechanism of LUP for treating diabetes is closely related to improving IR. LUP has the potential to develop as a new drug for the treatment of type 2 diabetes.