{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T15:58:47Z","timestamp":1782316727878,"version":"3.54.5"},"reference-count":58,"publisher":"PAGEPress Publications","issue":"3","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Histochem"],"abstract":"<jats:p>Chronic kidney disease (CKD) impacts a vast number of individuals worldwide, culminating in renal fibrosis. Renal fibrosis serves as the main reason for end-stage renal failure. However, the current targeted treatment methods for renal fibrosis remain scarce. Aloe-emodin (AE) is a naturally occurring compound discovered in rhubarb and aloe. In this research, we investigated the underlying mechanisms of AE in adenine-induced mouse renal fibrosis models and TGF\u03b2-1 stimulated renal tubular epithelial cells (HK-2). It was discovered that AE not only decelerated the decline of renal function in adenine-treated mice but also suppressed the expression of Collagen I and Fibronectin. Furthermore, network pharmacology analysis suggested that AE's treatment of renal fibrosis might function via the PI3K\/Akt\/GSK3\u03b2 signaling pathway. In vivo and in vitro Western blot and immunofluorescence findings demonstrate that AE significantly resists the advancement of renal fibrosis by inhibiting \u03b1-smooth muscle actin (\u03b1-SMA) and vimentin. Simultaneously, findings from 740Y-P (a PI3K agonist) and siRNA (PI3K) indicate that AE inhibits the expression of the PI3K\/Akt\/GSK3\u03b2 cascade by lowering PI3K's phosphorylation level. From a mechanistic perspective, through molecular docking and plasmid transfection, the specific base sequence of PI3K in HK-2 cells was altered for experimental validation. The outcomes illustrate that AE can directly bind with PI3K, inhibiting its activation, impeding the PI3K\/Akt\/GSK3\u03b2 signal transmission, thereby ultimately suppressing renal fibrosis progression. In conclusion, PI3K\/Akt\/GSK3\u03b2 is a potential therapeutic target for CKD-related renal fibrosis, making AE a promising new treatment alternative for this condition.<\/jats:p>","DOI":"10.4081\/ejh.2025.4228","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T11:01:10Z","timestamp":1754478070000},"source":"Crossref","is-referenced-by-count":4,"title":["Aloe-emodin ameliorates chronic kidney disease fibrosis by inhibiting PI3K-mediated signaling 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