Related Experiment Video

Updated: May 24, 2025

Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids

Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids

Published on: June 2, 2023

Monotropein inhibits epithelial-mesenchymal transition in chronic colitis via the mTOR/P70S6K pathway

Yuanfan Chen^1,2,3, Jiaying Liu¹, Shaowen Zhong¹

¹School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Frontiers in Pharmacology

|March 5, 2025

Abstract

Introduction:

Patients with chronic colitis are 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 aimed to investigate the effect of monotropein on EMT in chronic colitis and its underlying mechanism.

Methods:

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 analyzer. 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 cells. Western blot, real-time quantitative PCR, and immunofluorescence were used to test the inhibitory effect of monotropein on the development of EMT and explore its mechanism.

Results:

Results showed that monotropein significantly improved colonic injury and 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 validated 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.

Discussion:

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 the mTOR/P70S6K pathway.

Insights

Monotropein, derived from traditional Chinese medicine, effectively inhibits intestinal fibrosis in chronic colitis by blocking epithelial-mesenchymal transition (EMT). This action is linked to the mTOR/P70S6K pathway, offering a potential therapeutic strategy for colitis-associated fibrosis.

Area of Science:

Gastroenterology
Pharmacology
Cell Biology

Background:

Chronic colitis poses a risk of intestinal fibrosis via epithelial-mesenchymal transition (EMT).
Monotropein (MON), from *Morinda officinalis*, may improve ulcerative colitis, but its mechanism and effect on fibrosis are unknown.
Investigating MON's impact on EMT in chronic colitis is crucial for understanding its therapeutic potential.

Purpose of the Study:

To investigate the effect of monotropein on epithelial-mesenchymal transition (EMT) in chronic colitis.
To elucidate the underlying molecular mechanisms of monotropein's action in colitis-associated fibrosis.

Main Methods:

A mouse model of chronic colitis was induced using dextran sodium sulfate (DSS).
Monotropein's inhibitory effect on EMT was assessed in vivo and in vitro using TGF-β1-induced IEC-6 cells.
Molecular docking, MD simulations, CETSA, and DARTS assays identified monotropein's target as mTOR.

Main Results:

Monotropein significantly ameliorated colonic injury and suppressed EMT markers in DSS-induced colitis.
Monotropein directly targets mTOR, inhibiting its phosphorylation and downstream signaling in both cell and animal models.
Increased autophagy activity was observed in response to monotropein treatment.

Conclusions:

Monotropein effectively inhibits EMT in chronic colitis, suggesting a role in preventing intestinal fibrosis.
The therapeutic effect of monotropein is mediated through the mTOR/P70S6K signaling pathway.
Monotropein presents a promising therapeutic agent for managing chronic colitis-associated intestinal fibrosis.

Read full analysis

Keywords:

DSS chronic colitis epithelial–mesenchymal transition mTOR/P70S6K monotropein

More Related Videos

Induction and Analysis of Epithelial to Mesenchymal Transition

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

Related Concept Videos

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Articles linked to this work by shared authors, journal, and citation graph.

Design of a Photo-Assisted Electrochemical Potentiostat for Preconcentration-Free Detection of Heavy Metal Copper Ions.

Sensors (Basel, Switzerland)·2026

Impacts of particle morphology and rotation on optical manipulation.

Light, science & applications·2026

Tailored Surface Microenvironment of Molecular Nanophotocatalysts for Boosting Photocatalytic Hydrogen Evolution.

Advanced materials (Deerfield Beach, Fla.)·2026

Hydroxyl-radical-specific cascade photogeneration for oxygen-chain photocatalytic therapy.

Chemical science·2026

Electrochemically induced CoNiOOH Nanosheets enabling nitrite detection through a catalytic reduction mechanism and machine learning-based concentration prediction.

Food chemistry·2026

Electrochemical sensing device based on Cu/PPy heterostructure: Detection of nitrite at low reduction potentials and machine learning-driven data analysis visualisation.

Journal of hazardous materials·2026

See all related articles