Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Catalpol attenuates EMT by inhibiting Wnt/β-catenin and TGF-β/Smads signaling to alleviate kidney fibrosis

Hong-yan Gao¹, Tao-ren Ruan^2,3, Mao Xing⁴, Yi Chen², Shu-tong Bai¹, Jin-kun Liu¹, Xiao-wen Yu¹, Jing Feng¹, Xiao-yu Xu², Qin Wang^1,3

¹Chongqing Key Laboratory of Traditional Chinese Medicine to Prevent and Treat Autoimmune Diseases, Chongqing Hospital of Traditional Chinese Medicine, The Fourth Affiliated Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Chongqing 400021, China; ²College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400716, China; ³Department of Pharmacy, Chongqing Hospital of Traditional Chinese Medicine, The Fourth Affiliated Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Chongqing 400021, China; ⁴Department of Pharmacy, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.

For correspondence:- Qin Wang Email: wqin1127@cdutcm.edu.cn Tel:+862367063732

Accepted: 4 January 2024 Published: 30 January 2024

Citation: Gao H, Ruan T, Xing M, Chen Y, Bai S, Liu J, et al. Catalpol attenuates EMT by inhibiting Wnt/β-catenin and TGF-β/Smads signaling to alleviate kidney fibrosis. Trop J Pharm Res 2024; 23(1):57-65 doi: 10.4314/tjpr.v23i1.8

© 2024 The authors.
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Abstract

Purpose: To determine the anti-fibrosis effect and underlying mechanism of action of catalpol (CAT) in chronic kidney disease (CKD).

Methods: Forty (40) rats were randomly divided into a sham group (10 rats) and a unilateral ureteral obstruction (UUO) model group (30 rats) which was further randomly subdivided into three groups of ten (10) rats each: the UUO model group, UUO + CAT low-dose group, and UUO + CAT high-dose group. HK-2 cells were stimulated with TGF-β1 for in vitro studies. Renal injury and fibrotic lesions were determined by H&E and Masson’s staining. Key proteins of TGF-β/Smads and Wnt/β-catenin signaling pathways involved in epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, immunofluorescence staining and Western blotting.

Results: Catalpol downregulated the expression of α-SMA (p < 0.05) and upregulated the expression of E-cadherin (p < 0.05) stimulated by TGF-β1 and LiCl in HK-2 cells, which is consistent with the role of DKK1 in vitro. CAT ameliorated renal fibrosis and repressed the expression of key proteins of TGF-β/Smads and Wnt/β-catenin pathways in UUO rats.

Conclusion: Catalpol inhibits EMT and alleviates kidney fibrosis by suppressing the hyperactivation of TGF-β/Smad and Wnt/β-catenin signaling pathways. Therefore, CAT is a promising therapeutic drug for renal fibrosis.

Keywords: Catalpol, Renal fibrosis, Wnt/β-catenin signaling pathway, Epithelial-mesenchymal transition (EMT), TGF-β/Smads signaling pathway