title: Silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells.
abstract: BACKGROUND
  Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells.
  
  
  METHODS
  Cell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) secreted protein levels and mRNA levels were measured by the ELISA assay and RT-PCR, respectively. The NF-κB promoter activity was examined by a luciferase assay.
  
  
  RESULTS
  Silibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-κB through inhibition of the phosphorylation of IκBα and suppressed NF-κB transcriptional activity in stimulated HMC-1 cells.
  
  
  CONCLUSIONS
  Taken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.
authors.affiliation: Department of Oriental Medicine, Gachon University, 1342 Seongnamdaero, Sujeong Gu, Seongnam, Gyeonggi Do, 461-701, Republic of Korea.
authors.forename: Beom-Rak
authors.initials: BR
authors.lastname: Kim
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Seo
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Ku
authors.forename: Gyung-Jun
authors.initials: GJ
authors.lastname: Kim
authors.forename: Chan Yong
authors.initials: CY
authors.lastname: Jeon
authors.forename: Jong Hyeong
authors.initials: JH
authors.lastname: Park
authors.forename: Bo-Hyoung
authors.initials: BH
authors.lastname: Jang
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Yong-Cheol
authors.initials: YC
authors.lastname: Shin
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D012838:Silymarin; D000077385:Silybin; D051550:I-kappa B Kinase
references.citation: Nat Rev Immunol. 2001 Nov;1(2):135-45
references.pmid: 11905821
references.citation: Ann Otol Rhinol Laryngol. 2008 Oct;117(10):781-5
references.pmid: 18998509
references.citation: Experientia. 1988 May 15;44(5):459-62
references.pmid: 3131155
references.citation: Clin Exp Immunol. 2007 Feb;147(2):227-35
references.pmid: 17223962
references.citation: Exp Dermatol. 2000 Apr;9(2):118-24
references.pmid: 10772385
references.citation: J Leukoc Biol. 2004 Nov;76(5):1075-81
references.pmid: 15316034
references.citation: J Hepatol. 2003 Sep;39(3):333-40
references.pmid: 12927918
references.citation: Immunol Cell Biol. 2001 Apr;79(2):132-40
references.pmid: 11264706
references.citation: Biochem Biophys Res Commun. 2000 Dec 9;279(1):298-304
references.pmid: 11112456
references.citation: Int Immunopharmacol. 2006 Sep;6(9):1387-93
references.pmid: 16846832
references.citation: Eur Respir J. 2005 Oct;26(4):744-5; author reply 745-6
references.pmid: 16204608
references.citation: Nat Rev Immunol. 2002 Jun;2(6):446-53
references.pmid: 12093011
references.citation: Immunol Allergy Clin North Am. 2011 Aug;31(3):433-9
references.pmid: 21737035
references.citation: Cell Cycle. 2009 Oct 1;8(19):3125-32
references.pmid: 19738427
references.citation: Arch Pharm Res. 2008 Feb;31(2):225-30
references.pmid: 18365694
references.citation: J Ethnopharmacol. 2008 Mar 5;116(2):223-7
references.pmid: 18242903
references.citation: J Pharmacol Sci. 2010;113(1):48-56
references.pmid: 20431246
references.citation: Adv Exp Med Biol. 2011;716:123-42
references.pmid: 21713655
references.citation: Inflamm Res. 2006 Sep;55(9):393-8
references.pmid: 17122961
references.citation: Oncogene. 1995 Jul 6;11(1):97-106
references.pmid: 7624137
references.citation: Chem Pharm Bull (Tokyo). 1987 Feb;35(2):861-4
references.pmid: 3594697
references.citation: Nutr Res Pract. 2008 Winter;2(4):247-51
references.pmid: 20016726
references.citation: Nature. 2008 Jul 24;454(7203):445-54
references.pmid: 18650915
references.citation: Biol Pharm Bull. 2009 May;32(5):868-75
references.pmid: 19420756
references.citation: Proc Natl Acad Sci U S A. 2005 May 3;102(18):6467-72
references.pmid: 15840716
references.citation: Clin Cancer Res. 2006 May 1;12(9):2944-50
references.pmid: 16675592
references.citation: Nat Rev Immunol. 2007 Feb;7(2):93-104
references.pmid: 17259966
references.citation: Mol Endocrinol. 1996 Jun;10(6):713-22
references.pmid: 8776731
references.citation: Drug Metab Dispos. 2008 Mar;36(3):589-96
references.pmid: 18048488
references.citation: Br Dent J. 2011 Oct 21;211(8):369-70
references.pmid: 22015513
references.citation: J Exp Med. 2003 Jul 7;198(1):145-51
references.pmid: 12835479
references.citation: J Exp Med. 1992 Feb 1;175(2):489-93
references.pmid: 1370686
references.citation: Curr Med Chem. 2007;14(3):315-38
references.pmid: 17305535
references.citation: Anticancer Res. 2003 May-Jun;23(3B):2649-55
references.pmid: 12894553
references.citation: Mol Med Rep. 2010 May-Jun;3(3):427-32
references.pmid: 21472257