N'-[(3-[benzyloxy]benzylidene]-3,4,5-trihydroxybenzohydrazide (1) protects mice against colitis induced by dextran sulfate sodium through inhibiting NFκB/IL-6/STAT3 pathway.
IBD has attracted much attention for its negative influence on the quality of life and increased risk of colorectal cancer. In this study, we discovered the inhibitory activity of the polyphenol compound (1) in DSS induced colitis in mice by targeting NFκB/IL-6/STAT3 pathway. This compound effectively protected against body weight loss and colon length shortening induced by DSS. Additionally, 1 inhibited DSS induced damage in colon, notably decreasing the severity of inflammation, the extent of inflammation, crypt damage and percent involvement. The production of inflammatory mediators of IL-6 and COX-2 was also significantly attenuated when treated with 1. It may be attributed to inhibiting NFκB signaling. Moreover, this polyphenol suppressed p-STAT3 production as well as its downstream proteins response for apoptosis, such as Bcl-2 and Bax. In summary, the study not only afforded our understanding involved in colitis, but also provided the possible therapy for human with IBD.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Meiyang
M
Xi
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. Electronic address: wangxiaojian@imm.ac.cn.
Xiaojian
X
Wang
Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Jun
J
Ge
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. Electronic address: yindali@imm.ac.cn.
Dali
D
Yin
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D016264:Dextran Sulfate; D004305:Dose-Response Relationship, Drug; D005260:Female; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology*; D059808:Polyphenols / Q000008:administration & dosage*; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016328:NF-kappa B; D059808:Polyphenols; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016264:Dextran Sulfate
Colitis; DSS; NFκB; STAT3