AUTHOR=Shanshan Jiang , Shu Pan , Xiao Hu , Kuerban Kudelaidi , Hao Zhu , Yujie Wang , Rong Wang , Yuhuan Shi , Yongfang Yuan 

TITLE=Modulating the gut microbiota and inflammation is involved in the effect of diosgenin against diabetic nephropathy in rat

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1555849

DOI=10.3389/fphar.2025.1555849

ISSN=1663-9812

ABSTRACT=BackgroundDiabetic nephropathy (DN) is a severe complication of diabetes, which has been increasingly associated with gut microbiota dysbiosis and inflammatory dysregulation.ObjectiveThis study investigates the dual therapeutic potential of diosgenin (DIO), a steroidal sapogenin, in modulating the gut-kidney axis and NLRP3 inflammasome activity in a streptozotocin (STZ)-induced DN rat model.MethodsOral DIO administration (20 mg/kg, 8 weeks) was used to treat the DN rats. The study assessed the effects on metabolic and renal function parameters, renal apoptosis and fibrosis, gut microbiota diversity, and NLRP3 inflammasome activation in the kidney.ResultsDIO treatment ameliorated the progression of DN, improving metabolic and renal function. It attenuated renal apoptosis and fibrosis and restored gut microbiota diversity, particularly enriching the abundance of Lachnospiraceae and Eubacterium. Mechanistically, DIO suppressed NLRP3 inflammasome activation in the kidney, disrupted the LPS-TLR4/NF-κB signaling cascade, and reduced systemic pro-inflammatory cytokines (IL-1β, IL-6).ConclusionDIO is a multitarget agent that addresses both gut microbiota homeostasis and NLRP3-driven inflammation, presenting a novel therapeutic strategy for DN through modulation of the gut-kidney axis.