Propolis Suppresses UV-Induced Photoaging in Human Skin through Directly Targeting Phosphoinositide 3-Kinase

Nutrients. 2020 Dec 10;12(12):3790. doi: 10.3390/nu12123790.


Propolis is a resinous substance generated by bees using materials from various plant sources. It has been known to exhibit diverse bioactivities including anti-oxidative, anti-microbial, anti-inflammatory, and anti-cancer effects. However, the direct molecular target of propolis and its therapeutic potential against skin aging in humans is not fully understood. Herein, we investigated the effect of propolis on ultraviolet (UV)-mediated skin aging and its underlying molecular mechanism. Propolis suppressed UV-induced matrix metalloproteinase (MMP)-1 production in human dermal fibroblasts. More importantly, propolis treatment reduced UV-induced MMP-1 expression and blocked collagen degradation in human skin tissues, suggesting that the anti-skin-aging activity of propolis can be recapitulated in clinically relevant conditions. While propolis treatment did not display any noticeable effects against extracellular signal-regulated kinase (ERK), p38, and c-jun N-terminal kinase (JNK) pathways, propolis exerted significant inhibitory activity specifically against phosphorylations of phosphoinositide-dependent protein kinase-1 (PDK1) and protein kinase B (Akt). Kinase assay results demonstrated that propolis can directly suppress phosphoinositide 3-kinase (PI3K) activity, with preferential selectivity towards PI3K with p110α and p110δ catalytic subunits over other kinases. The content of active compounds was quantified, and among the compounds identified from the propolis extract, caffeic acid phenethyl ester, quercetin, and apigenin were shown to attenuate PI3K activity. These results demonstrate that propolis shows anti-skin-aging effects through direct inhibition of PI3K activity.

Keywords: UV; matrix metalloproteinase-1; phosphoinositide 3-kinase; propolis; skin.

MeSH terms

  • Apigenin / pharmacology
  • Caffeic Acids / pharmacology
  • Collagen / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblasts / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 1
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plant Extracts / pharmacology*
  • Propolis / pharmacology*
  • Quercetin / pharmacology
  • Skin / metabolism
  • Skin Aging / drug effects*
  • Ultraviolet Rays / adverse effects


  • Caffeic Acids
  • Plant Extracts
  • Apigenin
  • Collagen
  • Propolis
  • Quercetin
  • Extracellular Signal-Regulated MAP Kinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol