Network pharmacology, molecular docking, and experimental verification reveal the mechanism of Yi-Shen-Hua-Shi granules treating acute kidney injury.

Ethnopharmacological Relevance: Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function.

Aim Of The Study: To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI.

Materials And Methods: Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted. The AKI model was induced by sepsis using the cecal ligation and puncture (CLP) technique. Prior to the operation, YSHSG was administered intragastrically once daily for 1 week. Blood and kidney tissues were collected 48 h post-CLP to verify the network pharmacology analysis.

Results: The core target proteins of YSHSG in the treatment of sepsis-induced AKI include AKT1, JUN, IL6, PTGS2, NFKBIA, MAPK3, Caspase-3 and MMP9, which were further confirmed by molecular docking. Pathway analyses such as Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) show that YSHSG plays a role in protecting the kidneys from sepsis-induced AKI through the PI3K/AKT, TNF, and IL17 signaling pathways. These findings were validated using qPCR and western blotting. In vivo experiments demonstrated that YSHSG inhibits the activation of TNF and IL17 signaling pathways while protecting against deactivation of the PI3K/AKT signaling pathway in sepsis-induced AKI. YSHSG also exhibits an effect on attenuating inflammation response and pyroptosis processes associated with the PI3K/AKT, TNF, and IL17 signaling pathways.

Conclusion: YSHSG mitigated sepsis-induced AKI by influencing the PI3K/AKT, TNF, and IL17 signaling pathways associated with inflammation and pyroptosis.