Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice.
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.
Han
Mi Hwa
MH
Bioevaluation Center, KRIBB, Cheongwon, Chungbuk, Republic of Korea.
Yoon
Won Kee
WK
Lee
Hyunju
H
Han
Sang-Bae
SB
Lee
Kiho
K
Park
Song-Kyu
SK
Yang
Kyu-Hwan
KH
Kim
Hwan Mook
HM
Kang
Jong Soon
JS
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
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