title: Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice.
abstract: Irritant contact dermatitis (ICD) is a non-allergic local inflammatory reaction of a skin and one of the most frequent occupational health problems. Silymarin has been clinically used in Europe for a long time to treat liver diseases and also known to have anti-cancer and anti-inflammatory activities. In the present study, we report that topical application of silymarin reduces chemical-induced ICD. Topical application of 2,4-dinitrochlorobenzene (DNCB) induced an ear swelling in BALB/c mice and silymarin suppressed DNCB-induced increase in ear thickness. Prophylactic and therapeutic application of silymarin showed similar effect on DNCB-induced increase in ear thickness and skin water content. In addition, phobor ester- or croton oil-induced increase in ear thickness was also inhibited by silymarin treatment. Silymarin also blocked neutrophil accumulation into the ear induced by these irritants. Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT. Silymarin also blocked TNF-alpha- and DNCB-induced NF-kappaB activation in HaCaT. Collectively, these results demonstrate that topically applied silymarin inhibits chemical-induced ICD in mice and this might be mediated, at least in part, by blocking NF-kappaB activation and consequently inhibiting the expression of cytokines and adhesion molecules.
authors.affiliation: Bioevaluation Center, KRIBB, Cheongwon, Chungbuk, Republic of Korea.
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Han
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Yoon
authors.forename: Hyunju
authors.initials: H
authors.lastname: Lee
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Yang
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002478:Cells, Cultured; D003436:Croton Oil; D017453:Dermatitis, Irritant / Q000188:drug therapy* / Q000378:metabolism; D004137:Dinitrochlorobenzene; D019040:E-Selectin / Q000235:genetics; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D012838:Silymarin / Q000008:administration & dosage*; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
chemical_list: D004137:Dinitrochlorobenzene; D019040:E-Selectin; D016209:Interleukin-8; D016328:NF-kappa B; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003436:Croton Oil; D013755:Tetradecanoylphorbol Acetate