Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Xuebijing injection (XBJ), one of the classical prescriptions for treating inflammation-related diseases, has been used to chronic obstructive pulmonary disease (COPD) in clinical practice. However, its molecular mechanism is still unclear. Network pharmacology combined with Affymetrix arrays and molecular docking techniques were applied to explore the molecular mechanism of XBJ for COPD. Predictive analysis of 728 active compounds in XBJ and 6 sets of Affymetrix arrays expression data resulted in 106 potential therapeutic targets. Next, based on the active compound-co-target network topology analysis, most of these targets were found to be modulated by quercetin, myricetin, and ellagic acid. Furthermore, protein-protein interaction (PPI) analysis revealed that the key targets may be EGFR, STAT3, AKT1, CCND1, MMP9, AR, ESR1, and PTGS2. Then, by constructing a component-target-pathway network, we found that XBJ was a multi-pathway, multi-target, multi-compound synergistic therapy for COPD, and four key targets were involved in the FoxO signaling pathway. Luteolin and salvianolic acid b had the optimal binding ability to several key proteins. Therefore, we hypothesize that quercetin, myricetin, ellagic acid, luteolin, and salvianolic acid b mainly contribute to the therapeutic effect of XBJ on COPD by modulating the FoxO signaling pathway by regulating EGFR, STAT3, AKT1, and CCND1. XBJ exerts anti-inflammatory and antioxidative stress effects through the PI3K/Akt/FoxO axis combined with MMP9, AR, ESR1, and PTGS2 to regulate other signaling pathways.