Rutaecarpine analogues with potent anti-inflammation to alleviate acute ulcerative colitis via regulating TLR4/MAPK/NF-B pathway

Natural products are a rich resource in drug discovery. In the report, series novel rutaecarpine-derived compounds with potent anti-inflammatory activity and therapeutic efficacy against dextran sulfate sodium (DSS)induced ulcerative colitis (UC) were designed and synthesized. Thirty-two target compounds inhibiting on LPSinduced NO production in RAW264.7 cells were screened. Compound 7mA with the most potent inhibitory activity and low cytotoxicity was selected as representative compound for further studies on the antiinflammatory efficacy and mechanism. The results indicated that 7mA could significantly inhibit the transcription or expression of iNOS, IL-6 and IL-1 beta via regulating the TLR4/MAPK/NF-kappa B signal pathway. What's more, 7mA also could alleviate UC in DSS-induced mice, and down-regulated the release of IL-6, IL-1 beta, inhibited activation of TLR4/MAPK/NF-kappa B pathway in mice model as well, suggesting that this new rutaecarpine-derived scaffold might serve as therapeutic candidate for further development to anti-inflammatory agent.