Andrographolide derivative AL-1 ameliorates TNBS-induced colitis in mice: involvement of NF-кB and PPAR-γ signaling pathways.

Abstract

Andrographolide is a traditional herb medicine, widely used in Asia for conditions involving inflammation. The andrographlide-lipoic acid conjugate, AL-1, has been found being able to alleviate inflammation in our previous reports. Although the anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve inflammatory bowel disease (IBD) and the underlying mechanisms of its action remain largely unknown. In this study, we investigated the anti-inflammatory effects of AL-1 in C57BL/6 mice with trinitrobenzenesulfonic acid (TNBS)-induced colitis. The body weight loss and length change of colon after TNBS instillation were more severe than those in normal mice. AL-1 treatment led to significant reductions in disease activity index (DAI), macroscopic score and colon mucosa damage index (CMDI) associated with TNBS administration. AL-1 inhibited the inflammatory response via lowering the level of inflammatory cytokines and myeloperoxidase (MPO) activity. AL-1 attenuated the expression of p-p65, p-IκBα and COX-2 in the colitis mice. The alleviation of colon injury by AL-1 treatment was also evidenced by the increased expression of PPAR-γ. These results indicated that AL-1 could protect intestinal tract from the injury induced by TNBS in mice, suggesting that AL-1 may have potential in treatment for IBD.

• Authors: Yali Yang, Hui Yan, Mei Jing, Zaijun Zhang, Gaoxiao Zhang, Yewei Sun, Luchen Shan, Pei Yu, Yuqiang Wang, Lipeng Xu
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 29716 (07 20 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27435110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Diterpenes
• Inflammation Mediators
• NF-kappa B
• PPAR gamma
• andrographolide
• Thioctic Acid
• Trinitrobenzenesulfonic Acid
• Peroxidase

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Colitis (chemically induced, metabolism, prevention & control)
• Colon (drug effects, metabolism, pathology)
• Cytokines (metabolism)
• Diterpenes (chemistry)
• Inflammation Mediators (metabolism)
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• PPAR gamma (metabolism)
• Peroxidase (metabolism)
• Signal Transduction (drug effects)
• Thioctic Acid (chemistry)
• Trinitrobenzenesulfonic Acid