title: Lupeol inhibits LPS-induced NF-kappa B signaling in intestinal epithelial cells and macrophages, and attenuates acute and chronic murine colitis.
abstract: OBJECTIVE
  Lupeol, a natural pentacyclic triterpene, exhibits anti-inflammatory effects. However, its role in colitis has not been investigated. In the present study, we evaluated the effect of lupeol on the NF-κB signaling pathway and experimental colitis in mice.
  
  
  METHODS
  The human intestinal epithelial cells (IECs) COLO 205 and the murine macrophages RAW 264.7 were pretreated with lupeol and then stimulated with lipopolysaccharide (LPS). The production of inflammatory cytokines (IL-8 from COLO 205; IL-6, IL-12 and TNF-α from RAW 264.7) was determined by ELISA. The effect of lupeol on NF-κB pathway was examined by Western blot analysis of IκBα phosphorylation/degradation and an electrophoretic mobility shift assay (EMSA). For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis model and chronic colitis model in IL-10(-/-) mice were used. Colitis was quantified by disease activity index, colon length and histologic evaluation.
  
  
  RESULTS
  Lupeol strongly suppressed pro-inflammatory cytokine production in IECs and murine macrophages. It also inhibited LPS-induced IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. The oral administration of lupeol significantly reduced the colitis activity and histologic scores in both acute and chronic murine colitis models. Furthermore, the up-regulation of IκBα phosphorylation in the colonic mucosa was attenuated in lupeol-treated mice.
  
  
  CONCLUSIONS
  Lupeol blocks the NF-κB signaling in IECs and murine macrophages, and attenuate experimental murine colitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel disease.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Changhyun
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong Pil
authors.initials: JP
authors.lastname: Im
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jooskim@snu.ac.kr.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002477:Cells; D003092:Colitis / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D000094042:Lupanes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016753:Interleukin-10; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; C556062:IL10 protein, mouse; C010480:lupeol; D000094042:Lupanes
keywords: Inflammatory bowel diseases; Lupeol; Mice; NF-kappa B; Pentacyclic triterpenes