2. Academic Validation
  3. Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer

Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer

  • Lab Invest. 2014 Sep;94(9):950-65. doi: 10.1038/labinvest.2014.89.
Emilie Viennois 1,  Bo Xiao 2,  Saravanan Ayyadurai 2,  Lixin Wang 1,  Peng G Wang 3,  Quan Zhang 4,  Yue Chen 4,  Didier Merlin 1
Affiliations

Affiliations

  • 1 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.
  • 2 Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
  • 3 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.
  • 4 The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
PMID: 25068660 DOI: 10.1038/labinvest.2014.89
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.

Figures
Products