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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.
Objective:
Numerous therapeutics and pharmacological properties have been reported in syringic acid (SA). In this study, we aimed to evaluate effect of SA in ulcerative colitis (UC) in rats considering effect on TLR4, NF-κB, and INOS pathways.
Materials And Methods:
48 Wistar rats were randomly designated into six groups (n = 8). UC was induced via intra-rectal administration of 7% acetic acid (0.8 ml). SA at doses of 10, 25, 50 mg/kg was administrated through gavage, and dexamethasone (2 mg/kg) administrated intra-peritoneally for 5 consecutive days. The macroscopic and histopathological damages as well as expression of inflammatory and apoptotic genes along with superoxide dismutase (SOD) and catalase (CAT) activities, total antioxidant capacity (TAC), nitric oxide (NO), and malondialdehyde (MDA) levels in the colon tissue were assessed.
Results:
UC led to an increase in the apoptotic and inflammatory genes, NO and MDA levels as well as decrease in TAC level, and SOD and CAT activities (p < 0.05). UC also caused severe damage, edema, inflammation, and necrosis in the colon. SA significantly reduced gene expressions of INOS, TLR4, IL-6, IL-1β, NF-κB, Caspase-3, Caspase-8, and Bax. SA ameliorated negative macroscopic and histopathologic effects of UC. SA significantly reduced MDA and NO levels, and increased TAC level and CAT activity in the colon tissue in comparison to the UC rats without treatment (p < 0.05).
Conclusion:
SA via attenuation of the TLR4-NF-κB, NF-κB-INOS-NO pathways, oxidative stress, inflammation, and apoptosis of UC in rats.
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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