Magnolol preserves the integrity of the intestinal epithelial barrier and mitigates intestinal injury through activation of PPAR γ in COPD rat

Abstract

Ethnopharmacological relevance

Magnolia officinalis Rehder & E.H. Wilson is traditionally used in the treatment of gastrointestinal disorders, diarrhea, and cough. Its main active ingredient, magnolol, exhibits protective effects on the lungs and gastrointestinal tract, including the inhibition of inflammation in these organs.

Aim of the study

This work aims to explore the molecular mechanism by which magnolol suppressed Chronic obstructive pulmonary disease (COPD) intestinal damage by improving the intestinal epithelial barrier.

Materials and methods

The study focused on investigating the mitigation effect of magnolol on intestinal injury and epithelial barrier in a COPD rat. Caco-2 cells were induced with TNF-α or IL-1β to establish the barrier injury model in order to explore the direct protective effect of magnolol on the intestinal barrier and elucidate the molecular mechanism by which it activates peroxisome proliferators-activated receptors-γ (PPARγ).

Results

Magnolol significantly improves pulmonary function and tissue damage in COPD rats by inhibiting inflammation, protease imbalance, and oxidative stress. It also suppresses colon tissue damage and inflammation, and protects colon epithelial barrier function by suppressing the decline of tight junction proteins, reducing colon epithelial permeability. In Caco-2 cells, magnolol directly reduces monolayer permeability, increases TEER, and upregulates tight junction protein expression induced by TNF-α or IL-1β. Drug Affinity Responsive Target Stability (DARTS) and thermal shift assays show that magnolol effectively binds to SRC, activating PPARγ signaling in Caco-2 cells and colon tissues of COPD rats. Furthermore, magnolol enhances the binding of PPARγ and RXRα, promoting their activation and entry into the nucleus. The PPARγ inhibitor GW9662 can reverse the effects of magnolol on PPARγ activation and tight junction protein upregulation in IL-1β or TNF-α induced Caco-2 cells.

Conclusions

This work demonstrates that magnolol enhances lung and intestinal functions in COPD rats, and elucidates its mechanism of action in protecting the intestinal epithelial barrier by activating PPARγ.