Anti-Fibrotic Effect of Oleamide Identified from the Moringa oleifera Lam. Leaves via Inhibition of TGF-β1-Induced SMAD2/3 Signaling Pathway

Document Type

Journal Article

Publication Date

4-4-2025

Journal

International journal of molecular sciences

Volume

26

Issue

7

DOI

10.3390/ijms26073388

Keywords

Moringa oleifera Lam.; TGF-β/SMAD2/3 pathway; anti-fibrotic effect; liver fibrosis; oleamide

Abstract

Moringa oleifera (MO) is a prominent plant in traditional medicine, widely recognized for its phytochemicals with anti-inflammatory properties. Liver fibrosis characterized by chronic inflammation and excessive extracellular matrix deposition may benefit from the therapeutic properties of MO. This report focuses on the potential of oleamide (OLA), a bioactive compound identified from MO, in mitigating liver fibrosis. The anti-fibrotic effects of OLA were evaluated by assessing the production of pro-inflammatory cytokines, gelatinase activity and the expression of genes and proteins associated with the TGF-β/SMAD2/3 pathway. The LX-2 human hepatic stellate cell line, in conjunction with TGF-β1, was employed to model fibrotic conditions. OLA treatment significantly reduced the production of pro-fibrotic effectors in the activated LX-2 cells. Molecular docking analysis demonstrated a high binding affinity of OLA to key proteins in the TGF-β/SMAD2/3 pathway, while qRT-PCR and Western blotting revealed that OLA suppressed the expression of COL1A1, COL4A1, SMAD2, SMAD3, SMAD4, MMP2, MMP9, ACTA2 and TIMP1. These findings indicate that OLA effectively attenuates the pro-inflammatory responses induced by TGF-β1 and inhibits the activation of LX-2 cells. Collectively, OLA holds significant potential as a therapeutic agent for the prevention and treatment of liver fibrosis via the modulation of the TGF-β/SMAD2/3 signaling pathway.

Department

Microbiology, Immunology, and Tropical Medicine

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