Network pharmacology prediction and experimental validation to explore the potential mechanism of Danggui Shaoyao San against Acute Kidney Injury

Ethnopharmacological relevance Acute kidney injury (AKI) is a growing worldwide health concern. Danggui Shaoyao San (DGSYS) was an frequently-used representative prescription to "promote blood and water and harmonize the body" in traditional Chinese medicine, and its underlying mechanism against AKI remains to be elucidated. Aim of the study To investigate the protective effect and potential molecular mechanism of DGSYS in alleviating AKI by network pharmacology and experiment validation. Materials and methods DGSYS was analyzed and separated by UHPLC. Network pharmacology, molecular docking and molecular dynamics simulation were used to screen the active ingredient-target pathway of DGSYS for AKI treatment. Meanwhile, the predictions were experimentally validated both in vivo and in vitro . Results 30 bioactive compounds and 821 non-repetitive targets were screened for DGSYS, and 292 potential DGSYS-AKI intersection targets were identified. According to the protein–protein interaction results and GO and KEGG analyses, we found that apoptosis mediated by SRC pathway exerted a vital role in DGSYS against AKI. In vivo experiments indicated that DGSYS mitigated I/R-induced kidney injury by suppressing SRC signaling pathway. Molecular docking and molecular dynamics simulation revealed that paeoniflorin (PF) have good binding affinity to SRC. Subsequently, in vitro experiments suggested that PF was the key bioactive compound against AKI from DGSYS by inhibiting SRC/ERK1/2 signaling pathway. Conclusion We exhibited the promising anti-AKI mechanism of DGSYS, and our findings also opened up an avenue for future basic experimental validation, indicating a novel research direction.