title: Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways.
abstract: OBJECTIVE
  To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori (H. pylori)-infected inflammation, intestinal metaplasia, and nuclear factor kappa B (NF-κB) signaling pathway in vitro.
  
  
  METHODS
  We used I-type H. pylori to infect human gastric epithelial gastric epithelium cell line (GES-1) cell lines, and then H. pylori-infected GES-1 cells were treated with radix curcumae (RC)-derived diterpenoid C of different concentrations (5, 10, 20 μg/mL) and amoxicillin. The expression of p65, IκB kinase (IKK) α and IKKγ proteins was detected with Western blotting, and the expression of interleukin (IL)-8, IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method. Data were analyzed using SPSS software ver18.0. For comparisons between groups of more than two unpaired values, one-way analysis of variance (ANOVA) was used. If an ANOVA F value was significant, post hoc comparisons were performed between groups. If results were not normally distributed, the Mann-Whitney U test was used to compare two groups of unpaired values, whereas for comparisons between groups of more than two unpaired values, the Kruskal-Wallis H test was used. Statistical significance was established at P < 0.05.
  
  
  RESULTS
  The MTT assay results revealed the inhibited rate of GES-1, and indicated that the IC5 of RC-derived diterpenoid C and amoxicillin all were 5 μg/mL for gastric GES-1 cells. The expression of IL-8 was significantly increased, especially at 12 h time point; and the expression of IL-4 was decreased in H. pylori-infected GES-1 cells. After H. pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin, the expression of IL-8 was decreased at 12, 24, 48, 72 h points (P < 0.01), especially in high-concentration diterpenoid C (20 μg/mL) group; and the expression of IL-4 was increased, especially in moderate and high-concentration diterpenoid C (10 and 20 μg/mL) groups. RC-derived diterpenoid C had the inhibitory effects on H. pylori-induced p65 translocation from cytoplasm into cell nucleus, H. pylori-stimulant IkBα degradation, the phosphorylation of p65 and IkBα, and the expression of IKKα and IKKβ proteins.
  
  
  CONCLUSIONS
  RC-derived diterpenoid C can block NF-κB signal pathway, effectively reducing the secretion of H. pylori-induced proinflammatory cytokine and increasing the secretion of anti-inflammatory cytokine.
authors: Department of Gastroenterology, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Xuan
authors: X
authors: Huang
authors: Bin
authors: B
authors: Lv
authors: Shuo
authors: S
authors: Zhang
authors: Qun
authors: Q
authors: Dai
authors: Bing-Bing
authors: BB
authors: Chen
authors: Li-Na
authors: LN
authors: Meng
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005756:Gastritis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D027343:Rhizome; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D004224:Diterpenes; C508598:IL4 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D010936:Plant Extracts; C498143:RELA protein, human; D051996:Transcription Factor RelA; C585952:diterpenoid C, Radix curcumae; D015847:Interleukin-4; C496559:CHUK protein, human; D051550:I-kappa B Kinase
keywords: Helicobacter pylori; Inflammatory cytokine; Nuclear factor-κB; Radix curcumae-derived diterpenoid C
references: Cancer Lett. 2007 Oct 28;256(2):207-17
references: 17640799
references: Cancer Sci. 2010 Jan;101(1):112-9
references: 19860845
references: Cancer Res. 2009 Oct 1;69(19):7595-602
references: 19773433
references: World J Gastroenterol. 2011 Aug 28;17(32):3691-9
references: 21990950
references: Nature. 2009 Jan 1;457(7225):102-6
references: 19122641
references: Biol Pharm Bull. 2009 Nov;32(11):1931-5
references: 19881312
references: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):618-23
references: 23267096
references: World J Gastroenterol. 2012 Feb 7;18(5):425-34
references: 22346248
references: World J Gastroenterol. 2012 Aug 21;18(31):4071-81
references: 22919237
references: Cancer Sci. 2008 May;99(5):836-42
references: 18294278
references: World J Gastroenterol. 2012 Dec 28;18(48):7371-7
references: 23326147
references: Cancer Sci. 2009 Jan;100(1):117-25
references: 19037990
references: Curr Med Chem. 2007;14(3):367-76
references: 17305539
references: Mol Carcinog. 2009 Aug;48(8):703-12
references: 19142899
references: J Immunol. 2013 Jan 15;190(2):549-55
references: 23248260
references: Cancer Sci. 2007 Mar;98(3):268-74
references: 17270016
references: World J Gastroenterol. 2012 Apr 7;18(13):1479-84
references: 22509079
references: Pharmacol Ther. 2009 Jan;121(1):1-13
references: 18950657
references: World J Gastroenterol. 2009 Sep 28;15(36):4547-55
references: 19777613
references: Dig Liver Dis. 2009 Dec;41(12):875-80
references: 19473897
references: J Mol Diagn. 2006 Nov;8(5):540-3
references: 17065421
references: J Hepatol. 2007 Sep;47(3):325-37
references: 17512084
references: Acta Biochim Pol. 2012;59(2):201-12
references: 22590694
references: World J Gastroenterol. 2012 Apr 14;18(14):1602-9
references: 22529688
references: J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1175-81
references: 18637055
references: Dis Esophagus. 2008;21(6):514-21
references: 18840136
references: Cell Signal. 2003 May;15(5):463-9
references: 12639709
references: Zhonghua Yi Xue Za Zhi. 2004 Jul 17;84(14):1210-1
references: 15387985
references: World J Gastroenterol. 2012 Jan 14;18(2):126-35
references: 22253518
references: Infect Immun. 2009 Apr;77(4):1337-48
references: 19179414
references: BMC Cancer. 2009 Jun 17;9:190
references: 19534809