Potential Mechanisms of 3, 4-Oxo-Isopropylidene-Shikimic Acid in Ameliorating 2, 4, 6-Trinitrobenzenesulfonic Acid-Induced Colitis in Rats.
Previously, we reported that 3, 4-oxo-isopropylidene-shikimic acid (ISA) has therapeutic potential in experimental colitis in rats. This study aimed to elucidate the potential mechanisms of ISA on the inflammatory response in rats with 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis. After the induction of colitis, rats were orally administered ISA for 12 days. Then, the expression levels of inflammatory cytokines, cell adhesion molecules, and matrix metalloproteinase (MMP) in the blood and colon tissues, and the protein level of nuclear factor kappa B (NF-κB) p65 in cytoplasm and nucleus of colon tissues were evaluated. As a result, an enhanced inflammatory response was observed in rats with experimental colitis. However, the treatment with ISA significantly ameliorated the inflammatory response, which was manifested as a significant decrease in the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-8, TNF-α mRNA, P-selectin, E-selectin, intercellular cell adhesion molecule-1, MMP9 and MMP9 mRNA in rat blood and colon tissues, respectively, and a significant decrease in the levels of IFN-γ/IL-4, and the NF-κBp65 activity coefficient. Therefore, the therapeutic effect of ISA on experimental colitis may be related to its inhibitory effect on the expression of cytokines, adhesion molecules, and MMP9, which may be involved in the inhibition of the activation and nuclear translocation of NF-κBp65.
['Yan|Yan|Y|', 'Wang|Pengchong|P|', 'Sun|Ying|Y|', 'Dong|Yalin|Y|', 'Xing|Jianfeng|J|']
D000818:Animals D003092:Colitis D016207:Cytokines D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D007249:Inflammation D008297:Male D008968:Molecular Conformation D051381:Rats D017207:Rats, Sprague-Dawley D012765:Shikimic Acid D014302:Trinitrobenzenesulfonic Acid
3 4-oxo-isopropylidene-shikimic acid cytokine cell adhesion molecule nuclear factor kappa B ulcerative colitis