title: Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice.
abstract: BACKGROUND
  Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice.
  
  
  METHODS
  The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2g/kg) and two positive drugs (sulfasalazine, SASP, 200mg/kg; and azathioprine, AZA, 13mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting.
  
  
  RESULTS
  The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment.
  
  
  CONCLUSIONS
  Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Qu
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: Yao-Xing
authors.initials: YX
authors.lastname: Dou
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: Qiong-Hui
authors.initials: QH
authors.lastname: Huang
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Zhi-Xiu
authors.initials: ZX
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xian
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, People's Republic of China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China.
authors.forename: You-Liang
authors.initials: YL
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Songshan Hu Industrial Park, Dongguan 523808, Guangdong, People's Republic of China. Electronic address: lxp88@gzucm.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.affiliation: Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Songshan Hu Industrial Park, Dongguan 523808, Guangdong, People's Republic of China. Electronic address: suziren@gzucm.edu.cn.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001379:Azathioprine / Q000494:pharmacology; D032269:Brucea / Q000737:chemistry*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004655:Emulsions; D008401:Gas Chromatography-Mass Spectrometry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012460:Sulfasalazine / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004655:Emulsions; D018836:Inflammation Mediators; D016328:NF-kappa B; D010938:Plant Oils; D012460:Sulfasalazine; D016264:Dextran Sulfate; D001379:Azathioprine
keywords: Brucea javanica oil emulsion; Dextran sulfate sodium; Inflammation; Nuclear factor kappa B; Ulcerative colitis