Network Pharmacological Screening of the Active Ingredients and Hypoglycemic Effect of Isodon rubescens in the Treatment of Diabetes

This study was firstly to study the relationship of "ingredient-target-pathway" and the pharmacological effects of Isodon rubescens for the treatment of diabetes. Based on a network pharmacology method, 138 active ingredients of Isodon rubescens were screened from the relative literatures, and their targets were confirmed by comparing these with the hypoglycemic targets in the DrugBank database. Results showed that Isodon rubescens contained 25 hypoglycemic ingredients, such as rabdoternin A, rabdoternin B, and epinodosinol. These ingredients could activate 6 hypoglycemic targets, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), integrin α-L (ITGAL), integrin β-2 (ITGB2), progesterone receptor (PGR), glucocorticoid receptor (NR3C1), and nuclear receptor subfamily 1 group I member 2 (NR1I2). These targets were involved in 94 signaling pathways, such as the Rap1, PI3K-Akt, and HIF-1 signaling pathways. The cell viability showed that the human umbilical vein endothelial cells (HUVECs) treated with alcohol extract (1.00 g/L) and the water extract (0.13 - 0.50 g/L) exhibited high viability compared to the model group (p < 0.05), respectively. 0In animal experiments, the rats treated with water extract of Isodon rubescens showed significant hypoglycemic effects compared to rats in the model group (p < 0.05). Overall, this approach provides an efficient strategy to explore hypoglycemic ingredients of Isodon rubescens and other traditional Chinese medicine.