Targets and Mechanisms of Xuebijing in the Treatment of Acute Kidney Injury Associated with Sepsis: A Network Pharmacology-based Study.

Abstract

Introduction: Sepsis is a state of the systemic inflammatory response of the host induced by infection, frequently affecting numerous organs and producing varied degrees of damage. The most typical consequence of sepsis is sepsis-associated acute kidney injury(SA-AKI). Xuebijing is developed based on XueFuZhuYu Decoction. Five Chinese herbal extracts, including Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix, make up the majority of the mixture. It has properties that are anti-inflammatory and anti-oxidative stress. Xuebijing is an effective medication for the treatment of SA-AKI, according to clinical research. But its pharmacological mechanism is still not completely understood.

Methods: First, the composition and target information of Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix were collected from the TCMSP database, while the therapeutic targets of SA-AKI were exported from the gene card database. To do a GO and KEGG enrichment analysis, we first screened the key targets using a Venn diagram and Cytoscape 3.9.1. To assess the binding activity between the active component and the target, we lastly used molecular docking.

Results: For Xuebijing, a total of 59 active components and 267 corresponding targets were discovered, while for SA-AKI, a total of 1,276 targets were connected. There were 117 targets in all that was shared by goals for active ingredients and objectives for diseases. The TNF signaling pathway and the AGE-RAGE pathway were later found to be significant pathways for the therapeutic effects of Xuebijing by GO analysis and KEGG pathway analysis. Quercetin, luteolin, and kaempferol were shown to target and modulate CXCL8, CASP3, and TNF, respectively, according to molecular docking results.

Conclusion: This study predicts the mechanism of action of the active ingredients of Xuebijing in the treatment of SA-AKI, which provides a basis for future applications of Xuebijing and studies targeting the mechanism.