Potent inhibitory effect of silibinin from milk thistle on skin inflammation stimuli by 12-O-tetradecanoylphorbol-13-acetate

Food Funct. 2015 Dec;6(12):3712-9. doi: 10.1039/c5fo00899a. Epub 2015 Sep 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Dermatitis / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Inflammation / drug therapy*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Milk Thistle / chemistry*
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Silybin
  • Silymarin / analysis
  • Silymarin / pharmacology*
  • Skin / drug effects
  • Skin / metabolism
  • Tetradecanoylphorbol Acetate
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Silymarin
  • Tumor Necrosis Factor-alpha
  • Silybin
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Tetradecanoylphorbol Acetate