biostudies-literatureUnknown16Cai Y<h4>Objective</h4>Yi-Shen-Hua-Shi (YSHS) granules are a widely utilized Chinese medicine formula for treating diabetic kidney disease (DKD). Although their effectiveness in treating DKD is established, the precise regulatory mechanism remains unclear. We aimed to explore the potential targets and mechanisms of action of YSHS in delaying DKD progression through network pharmacology and experimental validation.<h4>Methods</h4>Network pharmacology was employed to identify the potential targets and signaling pathways of YSHS in treating DKD, which was hypothesized to be associated with endoplasmic reticulum stress and apoptosis, and these predictions were validated through animal and cellular experiments. Following a 12-week YSHS intervention in db/db mice, assessments were conducted on blood Frontiers in pharmacology1586333https://www.ebi.ac.uk/biostudies/studies/S-EPMC12464004biostudies-literatureExploration of the renoprotective effect of Yi-Shen-Hua-Shi granules on db/db mice and the mechanism of podocyte apoptosis based on the GRP78/CHOP signaling pathway.PMC12464004Liu YJin GWang SZhang XCai YZhang MZhou XZhao ZZhou KfalseExploration of the renoprotective effect of Yi-Shen-Hua-Shi granules on db/db mice and the mechanism of podocyte apoptosis based on the GRP78/CHOP signaling pathway.<h4>Objective</h4>Yi-Shen-Hua-Shi (YSHS) granules are a widely utilized Chinese medicine formula for treating diabetic kidney disease (DKD). Although their effectiveness in treating DKD is established, the precise regulatory mechanism remains unclear. We aimed to explore the potential targets and mechanisms of action of YSHS in delaying DKD progression through network pharmacology and experimental validation.<h4>Methods</h4>Network pharmacology was employed to identify the potential targets and signaling pathways of YSHS in treating DKD, which was hypothesized to be associated with endoplasmic reticulum stress and apoptosis, and these predictions were validated through animal and cellular experiments. Following a 12-week YSHS intervention in db/db mice, assessments were conducted on blood 2025-01-01T00:00:00Z20252026-06-03T21:47:35.278Z2026-05-02T03:10:49.872ZS-EPMC124640044102001010.3389/fphar.2025.1586333