Network Pharmacology-Based Dissection of the Active Ingredients and Protective Mechanism of the Salvia Miltiorrhiza and Panax Notoginseng Herb Pair against Insulin Resistance

[Image: see text] The Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely utilized in traditional Chinese medicine for the longevity and for preventing and treating cardio-cerebrovascular diseases. Often associated with cardio-cerebrovascular diseases are comorbidities such as insulin resistance. However, the protective mechanisms of DQ against insulin resistance remain not well understood. Through network pharmacology analysis, a total of 94 candidate active compounds selected from DQ (61 from S. miltiorrhiza Bunge and 33 from P. notoginseng (Burk.) F. H. Chen) interacted with 52 corresponding insulin resistance-related targets, which mainly involved insulin resistance and the AMPK signaling pathway. Furthermore, the contribution index calculation results indicated 25 compounds as the principal components of this herb pair against insulin resistance. Among them, ginsenoside F2, protocatechuic acid, and salvianolic acid B were selected and validated to promote glucose consumption through activating AMPK phosphorylation and upregulating GLUT4 in insulin-resistant cell model (HepG2/IR) cells. These findings indicated that DQ has the potential for repositioning in the treatment of insulin resistance mainly through the AMPK signaling pathway.