Inhibition of TLR4, NF-κB, and INOS pathways mediates ameliorative effect of syringic acid in experimental ulcerative

Maryam Ghasemi-Dehnoo1,2, Hossein Amini-Khoei2, Zahra Lorigooini2

  • 1Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Inflammopharmacology
|December 14, 2023
PubMed
Abstract

Insights

Syringic acid (SA) effectively treats ulcerative colitis (UC) in rats by reducing inflammation and oxidative stress. This study shows SA

Area of Science:

  • Pharmacology and Toxicology
  • Gastroenterology
  • Molecular Biology

Background:

  • Syringic acid (SA) exhibits various reported therapeutic properties.
  • Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
  • The role of specific molecular pathways like TLR4, NF-κB, and INOS in UC pathogenesis is increasingly recognized.

Purpose of the Study:

  • To investigate the therapeutic effects of syringic acid (SA) on acetic acid-induced ulcerative colitis (UC) in a rat model.
  • To evaluate the impact of SA on key inflammatory and apoptotic pathways, including TLR4, NF-κB, and INOS.
  • To assess the antioxidant and anti-inflammatory potential of SA in the context of UC.

Main Methods:

  • Ulcerative colitis was induced in Wistar rats using intra-rectal acetic acid administration.
  • Rats were treated with varying doses of SA (10, 25, 50 mg/kg) or dexamethasone (2 mg/kg) for five consecutive days.
  • Macroscopic and histopathological damage, gene expression (inflammatory, apoptotic), antioxidant enzyme activities (SOD, CAT), TAC, NO, and MDA levels were assessed in colon tissue.

Main Results:

  • Acetic acid-induced UC significantly increased inflammatory markers, oxidative stress (NO, MDA), and apoptosis, while decreasing antioxidant capacity (TAC, SOD, CAT).
  • SA treatment dose-dependently ameliorated colon damage, reduced expression of INOS, TLR4, IL-6, IL-1β, NF-κB, Caspase-3, Caspase-8, and Bax.
  • SA significantly decreased MDA and NO levels and increased TAC and CAT activity compared to untreated UC rats.

Conclusions:

  • Syringic acid demonstrates significant therapeutic potential in managing ulcerative colitis in rats.
  • SA exerts its protective effects by attenuating the TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.
  • SA effectively reduces oxidative stress, inflammation, and apoptosis in the colon, offering a promising natural therapeutic agent for UC.

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