Dual Protective Effects of Flavonoids from Petasites japonicus against UVB-Induced Apoptosis Mediated via HSF-1 Activated Heat Shock Proteins and Nrf2-Activated Heme Oxygenase-1 Pathways

Biol Pharm Bull. 2017;40(6):765-773. doi: 10.1248/bpb.b16-00691.


The leaves of Petasites japonicus are used for their anti-allergic properties in traditional Korean, Japanese, and Chinese medicine. This study aimed to identify bioactive compounds isolated from P. japonicus leaves. All compounds were assessed for their ability of transcriptional activation, induction of phase 2 enzymes and heat shock proteins (HSPs), as well as protection against the UVB-induced apoptotic cell death. Bioactive compounds were isolated from P. japonicus leaves. All compounds were evaluated for their protective effect using human dermal fibroblasts (HDF) and human epidermal keratinocyte cells (HEKC) treated with UVB radiation. Four flavonoids were isolated from the leaves of P. japonicus and identified as kaempferol-3-O-(6″-acetyl)-β-D-glucoside (1), quercetin-3-O-(6″-acetyl)-β-D-glucoside (2), kaempferol-3-O-β-D-glucoside (3), and quercetin-3-O-β-D-glucoside (4). These compounds activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heat-shock response transcription elements (HSE) that resulted in the induction of heme oxygenase-1 (HO-1) and HSP70, respectively. Activation of these pathways provided protection to the skin cells against UVB radiation. The isolated compounds activated the Nrf2 and HSE pathways and could protect against UVB-induced apoptosis.

Keywords: Petasites japonicus; UVB radiation; antioxidant response element; apoptosis; heat-shock response transcription element; heme oxygenase-1.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line
  • Cell Survival / drug effects
  • Flavonoids / pharmacology*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat Shock Transcription Factors / metabolism*
  • Heat-Shock Proteins / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • NF-E2-Related Factor 2 / metabolism*
  • Petasites*
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Radiation-Protective Agents / pharmacology*
  • Signal Transduction / drug effects
  • Ultraviolet Rays / adverse effects*


  • Flavonoids
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Radiation-Protective Agents
  • HMOX1 protein, human
  • Heme Oxygenase-1