Abstract
Inflammatory bowel disease (IBD) is chronic inflammatory and relapsing disease of the gut. It has been known that activation of nuclear factor-κB (NF-κB) and production of proinflammatory cytokines play important roles in the pathogenesis of IBD. In this study, the effect of vanillin (4-hydroxy-3-methoxybenzaldehyde), a potent nuclear factor-κB (NF-κB) inhibitor, was evaluated in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of vanillin improved macroscopic and histological features of TNBS-induced colitis in a dose-dependent manner. Vanillin not only prevented TNBS-induced colitis but also ameliorated the established colitis. By in vivo NF-κB bioluminescence imaging, electrophoretic mobility shift assay, and Western blot, we found that vanillin suppressed in vivo NF-κB activities through the inhibition of p65 translocation, inhibitor of nuclear factor-κB(IκB)-α phosphorylation, and IκB kinase activation. Furthermore, vanillin reduced the expressions of proinflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α] and stimulated the expression of anti-inflammatory cytokine (IL-4) in colonic tissues. In conclusion, this work identified vanillin as an anti-inflammatory compound with the capacity to prevent and ameliorate TNBS-induced colitis. Due to its safety, vanillin could be a potent candidate for the treatment of IBD.
Footnotes
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This study was supported in part by the National Science Council [Grant NSC 97-2320-B-039-012-MY3]; the Committee on Chinese Medicine and Pharmacy at the Department of Health [Grants CCMP 96-RD-201, CCMP 97-RD-201]; and China Medical University [Grant CMU97-CMC-004].
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T.-Y.H. and C.-Y.H. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.109.152835.
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ABBREVIATIONS: IBD, inflammatory bowel disease; CD, Crohn's disease; TNBS, trinitrobenzene sulfonic acid; IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; NF-κB, nuclear factor-κB; 5-ASA, 5-aminosalicylic acid; sr, series resistance; EMSA, electrophoretic mobility shift assay; IKK, IκB kinase; IκB, inhibitor of nuclear factor-κB; PCR, polymerase chain reaction; Th, T-helper.
- Received February 26, 2009.
- Accepted May 6, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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