title: Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer.
abstract: Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal (GI) tract associated with an increased risk of colorectal cancer (CRC). Current treatments for both IBD and colitis-associated CRC suffer from numerous side effects. Parthenolide (PTL) is a sesquiterpene lactone with anti-inflammatory activity, and previous studies have demonstrated that PTL is a potent inhibitor of the NF-κB pathway. Micheliolide (MCL), substantially more stable than PTL in vivo, was recently developed, and this study aimed to decipher its suitability as therapeutic tool for IBD and IBD-associated diseases. Similar to PTL, MCL inhibited NF-κB activation and subsequent pro-inflammatory pathways activation in vitro. Pro-drug forms of both compounds inhibited the DSS-induced colitis when administrated intraperitoneally or encapsulated in a polysaccharide gel designed to release drugs in the colon. Interestingly, MCL was found to attenuate carcinogenesis in AOM/DSS-induced CRC, thus providing new candidate for the treatment of inflammatory bowel disease and CRC.
authors: 1] Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA [2] Veterans Affairs Medical Center, Decatur, GA, USA.
authors: Emilie
authors: E
authors: Viennois
authors: Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors: Bo
authors: B
authors: Xiao
authors: Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors: Saravanan
authors: S
authors: Ayyadurai
authors: 1] Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA [2] Veterans Affairs Medical Center, Decatur, GA, USA.
authors: Lixin
authors: L
authors: Wang
authors: 1] Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA [2] The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
authors: Peng G
authors: PG
authors: Wang
authors: The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
authors: Quan
authors: Q
authors: Zhang
authors: The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
authors: Yue
authors: Y
authors: Chen
authors: 1] Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA [2] Veterans Affairs Medical Center, Decatur, GA, USA.
authors: Didier
authors: D
authors: Merlin
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D003092:Colitis / Q000150:complications / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000150:complications / Q000517:prevention & control*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D045789:Sesquiterpenes, Guaiane / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D045789:Sesquiterpenes, Guaiane; C577928:micheliolide