Potent inhibitory effect of silibinin from milk thistle on skin inflammation stimuli by 12-O-tetradecanoylphorbol-13-acetate.
Silibinin, a major polyphenol in milk thistle, has been reported to have multiple pharmacological activities; therefore, there is an urgent need to well understand how silibinin works on inflammation-associated skin diseases. We herein designed silibinin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated skin inflammation to test its inhibitory effects. It was demonstrated that silibinin, applied topically onto mouse ears following TPA stimulation, effectively down-regulated the expressions of TPA-induced interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Further mechanistic investigations indicated that silibinin suppressed the expression of IκB kinase (IKK) by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and thereby suppressing TPA-stimulated nuclear factor-κB (NF-κB) activation. Promisingly, silibinin, used for transdermal application, may be a potent naturally occurring anti-inflammatory agent for the prevention of inflammation-associated skin diseases.
Laboratory of Natural Medicinal Chemistry & Green Chemistry, Faculty of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou, 510006, China. kzhang@gdut.edu.cn.
Wenfeng
W
Liu
Yonglian
Y
Li
Xi
X
Zheng
Kun
K
Zhang
Zhiyun
Z
Du
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020944:Silybum marianum / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000032:analysis / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013755:Tetradecanoylphorbol Acetate