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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1536091
This article is part of the Research Topic Immunomodulatory Natural Products - their Pharmacological and Therapeutic potential View all 10 articles
Monotropein inhibits epithelial-mesenchymal transition in chronic colitis via the mTOR/P70S6K pathway
Provisionally accepted
Yuanfan Chen 1* Shaowen Zhong 2* Tianwu Zhang 3* Jin Yuan 3* Jing Zhang 2* Ying Chen 2*
Jian Liang 2 Yonger Chen 2*
Haiyang Huang 4*
Shaozhen Hou 2* Jie Gao 2*- 1 University of the Visayas, Cebu, Philippines
- 2 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- 3 Pu’er Hospital of Traditional Chinese Medicine, Yunnan, China
- 4 Dongguan Hospital of Traditional Chinese Medicine, Dongguan, China
Chronic colitis is at risk of developing intestinal fibrosis through epithelial-mesenchymal transition (EMT). Monotropein (MON) is the main active ingredient in the traditional Chinese medicine Morinda officinalis How. It has been reported that monotropein can improve ulcerative colitis, but the mechanism remains unclear. However, whether monotropein can improve chronic colitis associated intestinal fibrosis remains unknown. The study is aim to investigate the effect of monotropein on EMT in chronic colitis and its underlying mechanism. The mice chronic colitis model was induced by dextran sodium sulfate (DSS). Cytokines were detected by ELISA. Concentrations of fluorescein isothiocyanate dextran (FITC-Dextran) in serum were detected using a fluorescein microplate analyser. Intestinal tight junction proteins were detected by immunofluorescence. EMT marker proteins were detected by immunohistochemistry. Transforming growth factor-β1 (TGF-β1) was used to induce EMT in IEC-6 cell. Western blot, real-time quantitative PCR and immunofluorescence were used to testify the inhibitory effect of monotropein on the development of EMT and explore its mechanism. Results showed that monotropein significantly improved the colonic injury, inhibited the expression of colonic tissue EMT marker protein. In addition, Molecular docking and molecular dynamics (MD) simulation, cellular thermal shift assay (CETSA) and Drug affinity responsive target stability (DARTS) assay validation of monotropein targeting of mTOR. Monotropein inhibited TGF-β1-induced EMT in IEC-6 cells, inhibited the phosphorylation of mTOR and its downstream proteins and increased the autophagy activity in chronic colitis mice and IEC-6 cells. The study indicates that monotropein inhibits the development of EMT in DSS-induced chronic colitis mice and TGF-β1-induced IEC-6 cells. Its inhibitory effect on EMT is associated with mTOR/P70S6K pathway.
Keywords: Monotropein, DSS, Epithelial-mesenchymal transition, mTOR/P70S6K Abbreviations: 5-ASA, 5-aminosalicylic acid, a-SMA, a-smooth muscle actin, DSS, dextran sodium sulfate, DAI, disease activity index, EMT, epithelial-mesenchymal transition, 4EBP1, eIF4E-binding protein 1, FITC-Dextran, fluorescein isothiocyanate dextran, H&E, hematoxylin-eosin
Received: 28 Nov 2024; Accepted: 21 Jan 2025.
Copyright: © 2025 Chen, Zhong, Zhang, Yuan, Zhang, Chen, Liang, Chen, Huang, Hou and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuanfan Chen, University of the Visayas, Cebu, 6000, Philippines
Shaowen Zhong, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Tianwu Zhang, Pu’er Hospital of Traditional Chinese Medicine, Yunnan, China
Jin Yuan, Pu’er Hospital of Traditional Chinese Medicine, Yunnan, China
Jing Zhang, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Ying Chen, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Yonger Chen, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Haiyang Huang, Dongguan Hospital of Traditional Chinese Medicine, Dongguan, China
Shaozhen Hou, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Jie Gao, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
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