title: Anti-inflammatory effect of a standardized triterpenoid-rich fraction isolated from Rubus coreanus on dextran sodium sulfate-induced acute colitis in mice and LPS-induced macrophages.
abstract: BACKGROUND
  Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.
  
  
  METHODS
  Experimental colitis was induced by DSS for 7 days in ICR mice. Disease activity indices (DAI) took into account body weight, stool consistency, and gross bleeding. Histological changes and macrophage accumulation were observed by immunohistochemical analysis. Pro-inflammatory markers were determined using immunoassays, RT-PCR, and real time PCR. Signaling pathway involving nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation was determined by luciferase assay and Western blotting.
  
  
  RESULTS
  In DSS-induced colitis mice, TFRC improved DAIs and pathological characteristics including colon shortening and colonic epithelium injury. TFRC suppressed tissue levels of pro-inflammatory cytokines and reduced macrophage infiltration into colonic tissues. In LPS-induced RAW 264.7 macrophages, TFRC inhibited the production of NO, PGE2, and pro-inflammatory cytokines by down-regulating the activation of NF-κB and p38 MAPK signaling.
  
  
  CONCLUSIONS
  The study demonstrates that TFRC has potent anti-inflammatory effects on DSS-induced colonic injury and LPS-induced macrophage activation, and supports its possible therapeutic and preventive roles in colitis.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Eu-Jin
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ji-Hyung
authors.initials: JH
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: An
authors.affiliation: Department of Botanical Resources, Sangji University, Gangwon-do, Republic of Korea.
authors.forename: Hee-Juhn
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. Electronic address: ktlee@khu.ac.kr.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers; D016264:Dextran Sulfate / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D065856:Rubus / Q000737:chemistry*; D014315:Triterpenes / Q000032:analysis*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014315:Triterpenes; D016264:Dextran Sulfate
keywords: Cytokine; Macrophage; NF-κB; Rubus coreanus; Ulcerative colitis; p38 MAPK