Serum and Urine Metabolite Profiling Combined With Network Pharmacology to Predict the Renoprotective Mechanism of Huangkui Capsule Against Acute Kidney Injury

Huangkui capsule (HKC), the ethanol extract of Abelmoschus Manihot (L.) Medicus, is well known for its nephroprotective effects against chronic kidney diseases, but its therapeutic potential in acute kidney injury (AKI) and the underlying mechanisms remain largely unexplored. In this study, a simple and reliable LC-Q-TOF/MS method was developed to detect HKC metabolites in rat serum and urine. A metabolite-disease target network was constructed to predict the pharmacological activities of the serum metabolites, followed by PPI network analysis for hub target identification and GO/KEGG enrichment analyses. A total of 41 urine and 28 serum metabolites were identified. Network pharmacology analysis revealed 50 targets associated with 15 metabolites in the context of HKC treatment of AKI. AKT1 and its related pathways were predicted to serve as a central hub, and molecular docking analysis further predicted favorable binding affinity between AKT1 and all six screened key metabolites. This study established a practical approach for identifying HKC metabolites in vivo and provided a systematic framework for predicting the anti-AKI mechanism of HKC.