Articles
Vol. 69 No. 3 (2025)
Aloe-emodin ameliorates chronic kidney disease fibrosis by inhibiting PI3K-mediated signaling pathway
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 6 August 2025
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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 TGFβ-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/GSK3β signaling pathway. In vivo and in vitro Western blot and immunofluorescence findings demonstrate that AE significantly resists the advancement of renal fibrosis by inhibiting α-smooth muscle actin (α-SMA) and vimentin. Simultaneously, findings from 740Y-P (a PI3K agonist) and siRNA (PI3K) indicate that AE inhibits the expression of the PI3K/Akt/GSK3β 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/GSK3β signal transmission, thereby ultimately suppressing renal fibrosis progression. In conclusion, PI3K/Akt/GSK3β is a potential therapeutic target for CKD-related renal fibrosis, making AE a promising new treatment alternative for this condition.
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Ethics Approval
Animal experiments in this study were conducted in accordance with the protocols approved by the Ethics Committee for Laboratory Animal Welfare of China-Japan Friendship HospitalSupporting Agencies
This work was supported by the National Natural Science Foundation of China (No. 82274489), the Beijing Natural Science Foundation of China (No. 7232326) and the Heilongjiang Provincial Natural Science Foundation of China (No. LH2021H070).Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon reasonable request
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1.
Chen M, Zhu W, Chen Y, Shang J, Wang W, Yan X, et al. Aloe-emodin ameliorates chronic kidney disease fibrosis by inhibiting PI3K-mediated signaling pathway. Eur J Histochem [Internet]. 2025 Aug. 6 [cited 2026 Jan. 19];69(3). Available from: https://www.ejh.it/ejh/article/view/4228
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