Guiqi Yishen granule alleviates obstructive nephropathy-induced renal fibrosis by targeting PI3K/AKT signaling pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Guiqi Yishen granule (GQYSG), a traditional Chinese medicine with a well-documented history in managing kidney diseases such as IgA nephropathy and diabetic nephropathy, has emerged as a potential therapeutic option for Obstructive nephropathy (ON). AIM OF THE STUDY: Obstructive nephropathy (ON) ranks as the third leading cause of CKD, yet effective treatments remain limited. This study aims to explore the therapeutic efficacy of GQYSG in alleviating ON-mediated renal fibrosis, identify the active compounds responsible for its beneficial effects, and elucidate the underlying mechanisms of action. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to UUO surgery to establish the ON model. The mice were administered GQYSG via oral gavage to evaluate its therapeutic effects. Histological and TEM analysis was performed to evaluate renal tissue damage. The mRNA and protein expression levels of EMT markers and proinflammatory cytokines in kidney samples were quantified using qRT-PCR and Western blot, respectively. LC-HRMS was employed to identify the active compounds in GQYSG, and RNA-seq was conducted to explore the molecular mechanisms underlying its effects. RESULTS: GQYSG significantly alleviated renal fibrosis in the ON mouse model. Among the compounds identified in GQYSG, five specific compounds enriched in kidney tissue demonstrated significant anti-fibrotic properties. Mechanistically, the PI3K/AKT signaling pathway was identified as the primary mediator of GQYSG's therapeutic effects. CONCLUSION: This study demonstrates that GQYSG attenuates renal fibrosis by modulating the PI3K/AKT signaling pathway. These findings highlight the therapeutic potential of GQYSG and provide a foundation for further research and development of TCM-based therapies for CKD.