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

Abstract

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. 48 Wistar rats were randomly designated into six groups (n = 8). UC was induced via intra-rectal administration of 7% acetic acid (0.8ml). SA at doses of 10, 25, 50mg/kg was administrated through gavage, and dexamethasone (2mg/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. 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). SA via attenuation of the TLR4-NF-κB, NF-κB-INOS-NO pathways, oxidative stress, inflammation, and apoptosis of UC in rats.