Integrated metabolomics and network pharmacology reveal the mechanisms of Xuebijing in counteracting sepsis-induced myocardial dysfunction
Yan Hu, Yang Xu, Jian Gao, Bingrui Ling, Sinong Pan, Siying Liu, Tianfeng Hua, Min Yang
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing (XBJ) injection is a Traditional Chinese medicine (TCM) injection extracted and prepared using modern TCM formulation techniques. As a widely used treatment for critically ill patients, XBJ injection has shown significant therapeutic effects in clinical applications in China. It plays an indispensable role in sepsis-induced myocardial dysfunction (SIMD). However, its underlying mechanisms require further investigation. OBJECTIVE: This study aims to investigate the cardioprotective effects of XBJ in sepsis and to elucidate its underlying mechanisms. METHODS: Network pharmacology was used to predict the potential active components and core targets of XBJ against SIMD. Furthermore, animal models were used to verify its pharmacodynamics. Metabolomics was integrated to track the myocardial tissue metabolites from septic rats. Molecular docking, qRT-PCR, Western blot, and immunofluorescence were performed to investigate the mechanisms of action. RESULTS: Network pharmacology predicted that the efficacy of XBJ is attributed to 104 active components and 178 targets. Metabolomics of myocardial tissue from CLP rats revealed that the key metabolic pathways included the tricarboxylic acid (TCA) cycle, pyrimidine metabolism, and purine metabolism. Five core active components of XBJ (quercetin, luteolin, rutin, β-sitosterol, and cryptotanshinone) can modulate interleukin-6 (IL-6), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (BCL2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and hypoxia-inducible factor 1-alpha (HIF-1α). Molecular docking analysis confirmed that the core components of XBJ have a strong affinity for these key targets. Additionally, qRT-PCR, Western blotting, and immunofluorescence results indicated that XBJ can reverse the expression of these targets, ameliorated energy metabolism dysregulation, and alleviated SIMD. CONCLUSION: XBJ exerts protective effects in a rat model of sepsis-induced myocardial injury, by modulating energy metabolism pathways that regulate key SIMD-related targets (IL-6, EGFR, BCL2, PGC-1α, and HIF-1α), thereby improving myocardial energy metabolism and alleviating inflammatory responses.