N-Methylcytisine Ameliorates Dextran-Sulfate-Sodium-Induced Colitis in Mice by Inhibiting the Inflammatory Response.

Abstract

This study aimed to investigate the anti-inflammatory effects of N-methylcytisine (NMC) in a dextran sulfate sodium (DSS)-induced colitis model and explore its possible mechanisms. Experimental colitis was induced by administering the mice with 5% DSS for 7 days. Different doses of NMC (1, 4 and 16 mg/kg) and 5-aminosalicylic acid (100 mg/kg) were given orally once every day for 7 days. The protective effect of NMC was evaluated using the disease activity index, colon length and results of histopathological examination. The possible mechanisms of NMC were explored by evaluating the expression levels of tumour necrosis factor-α, interleukin-1β and interleukin-6 (IL-6) using ELISA and analysing the protein expression levels of nuclear factor (NF)-κB p65, p-NF-κB p65, p-IκB, IκB, IκB kinase (IKK) and p-IKK using western blots. Results demonstrated that the oral administration of NMC attenuated the DSS-induced clinical symptoms and pathological damage. In addition, NMC treatment significantly reduced myeloperoxidase activity and level of pro-inflammatory cytokines. Further studies revealed that NMC blocked the activation of NF-κB by inhibiting IκB and IKK phosphorylation. These findings suggested that NMC exerts anti-inflammatory effects on DSS-induced colitis, and its mechanism may be related to the suppression of NF-κB activation. Thus, NMC may have potential therapeutic value in the treatment of colitis.

• Authors: Yan-Fang Jiao, Min Lu, Yu-Ping Zhao, Ning Liu, Ya-Ting Niu, Yang Niu, Ru Zhou, Jian-Qiang Yu
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 23 Issue 3 (Feb 25 2018) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 29495327 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• Anti-Inflammatory Agents
• Biomarkers
• Cytokines
• I-kappa B Proteins
• Inflammation Mediators
• Quinolizines
• Dextran Sulfate
• Peroxidase
• N-methylcytisine

Topics

• Alkaloids (chemistry, pharmacology)
• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Biomarkers
• Colitis (chemically induced, drug therapy, metabolism, pathology)
• Cytokines (metabolism)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• I-kappa B Proteins (metabolism)
• Inflammation Mediators (metabolism)
• Intestinal Mucosa (drug effects, metabolism, pathology)
• Mice
• Peroxidase (metabolism)
• Quinolizines (chemistry, pharmacology)