Pivotal role of AhR protein in the therapeutic efficacy of HuangKui capsule against calcium oxalate-induced kidney damage: An integrated study of network pharmacology and experimental verification

Kidney stone are a frequently-occurring disease that may lead to severe renal impairment and eventual renal malfunction. The Aryl Hydrocarbon Receptor (AhR) is a cytoplasmic receptor and transcription factor that belongs to the family of basic helix-loop-helix transcription factors, which plays an important role in the pathogenesis of kidney stones. The HuangKui Capsule (HKC) is a Traditional Chinese Medicine used for managing chronic glomerulonephritis. The purpose of this study is to investigate the therapeutic impact and mechanisms of HKC on kidney stone-related renal tubular injury. The findings revealed that HKC reduces calcium crystal deposition and promotes the repair of renal tubular injury in mice with kidney stones. Network pharmacology analysis predicted the active ingredients, potential targets, and pathways of HKC in improve renal tubular injury induced by kidney stones, which AhR is considered a key target for HKC to exert its effects. Molecular docking and molecular dynamics simulation analysis indicate that HKC and its active ingredients can act as potential ligands to activate AhR. The predicted results were confirmed by the enhanced AhR expression following HKC treatment. In vitro experiments further highlighted the role of AhR in the protective effect of HKC on kidney stone injury. In summary, through network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification, it has been found that HKC effectively inhibits renal tubular injury induced by kidney stones by targeting AhR.

AhR; Huangkui capsule; Kidney stones; Molecular dynamics simulations; Network pharmacology.