This study aimed to investigate the pharmacological effects and molecular mechanisms of Dahuang-Gancao Decoction (DHGC) on acute kidney injury (AKI). Network pharmacology was utilized to analyze the key targets of DHGC against AKI. These targets were used to construct a protein-protein interaction (PPI) network, which was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict the mechanism of action. Based on the network pharmacological analysis, Sirtuin 3 (SIRT3) was identified as a key target, and apoptosis was suggested as a mechanism of DHGC for AKI treatment. Subsequently, an AKI mouse model was induced using lipopolysaccharide (LPS), and the study demonstrated that DHGC gradient intervention significantly reduced plasma urea and creatinine levels in AKI mice, ameliorated renal pathological changes, reduced apoptosis, and lowered serum inflammatory factors. The mechanism of DHGC's anti-AKI effect may lie in the activation of the SIRT3/NRF2/HO-1 signaling pathway, which plays an antiapoptotic role in renal cells. In summary, DHGC improved LPS-induced AKI in mice by activating the SIRT3/NRF2/HO-1 signaling pathway. These findings shed light on the potential clinical application of DHGC for the treatment of nephropathy.
Keywords: Dahuang-Gancao decoction; SIRT3/NRF2/HO-1 signaling pathway; acute kidney injury; experimental validation; network pharmacology.