Cytoprotective effects of a proprietary red maple leaf extract and its major polyphenol, ginnalin A, against hydrogen peroxide and methylglyoxal induced oxidative stress in human keratinocytes

Food Funct. 2020 Jun 24;11(6):5105-5114. doi: 10.1039/d0fo00359j.


Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 μM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 μg mL-1) and GA (50 μM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 μg mL-1) and GA (50 μM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

MeSH terms

  • Acer / chemistry*
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Line
  • Cytoprotection
  • Deoxyglucose / analogs & derivatives*
  • Deoxyglucose / pharmacology
  • Down-Regulation
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Mitochondria / metabolism
  • Oxidative Stress*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Pyruvaldehyde / toxicity*
  • Reactive Oxygen Species / metabolism


  • Plant Extracts
  • Reactive Oxygen Species
  • ginnalin A
  • Gallic Acid
  • Pyruvaldehyde
  • Deoxyglucose
  • Hydrogen Peroxide
  • Caspases