Synergistic target network construction and dynamic simulation analysis based on a prospective systems pharmacology strategy.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, low-grade chronic inflammation, and insufficient insulin secretion, influenced by genetic predisposition and detrimental lifestyle choices. It leads to severe complications that significantly impair quality of life. Sang Huang, a rare and valuable medicinal fungus, has potential therapeutic value for T2DM, but its mechanisms remain underexplored. This study utilized network pharmacology to investigate Sang Huang therapeutic potential in T2DM, validated core targets via molecular docking and molecular dynamics simulations, and elucidated its mechanisms. Results demonstrated that estradiol dipropionate (EDP), a key component of Sang Huang, exerted anti-T2DM effects via pathways such as PI3K-Akt. Upon metabolism to estradiol, EDP activated estrogen receptors, triggering the PI3K-AKT1 signaling cascade, which regulates the phosphorylation of FoxO1, GSK3β, and mTORC1. This enhanced glucose-lipid metabolism; improved insulin sensitivity; and preserved β-cell function in the liver, skeletal muscle, and adipose tissue. Additionally, EDP promoted GLUT4 expression and membrane translocation via the AMPK pathway, accelerating glucose uptake and restoring glycemic homeostasis. Molecular docking further confirmed strong binding affinities between 5 active components and these core targets. Molecular dynamic simulations supported the stability of these interactions. Through this study, we have screened the relevant information of Sang Huang active ingredients and preliminarily predicted its potential targets and pathways for anti-T2DM, but further experimental verification is needed. The results of this study prospectively suggest the potential value of Sang Huang in the treatment of T2DM.