Hydrangenol Isolated from the Leaves of Hydrangea serrata Attenuates Wrinkle Formation and Repairs Skin Moisture in UVB-Irradiated Hairless Mice

Nutrients. 2019 Oct 2;11(10):2354. doi: 10.3390/nu11102354.


Our previous study showed that hydrangenol isolated from Hydrangea serrata leaves exerts antiphotoaging activity in vitro. In this study, we determined its antiphotoaging effect in UVB-irradiated HR-1 hairless mice. We evaluated wrinkle formation, skin thickness, histological characteristics, and mRNA and protein expression using qRT-PCR and Western blot analysis in dorsal skins. Hydrangenol mitigated wrinkle formation, dorsal thickness, dehydration, and collagen degradation. Hydrangenol increased the expression of involucrin, filaggrin, and aquaporin-3 (AQP3) as well as hyaluronic acid (HA) production via hyaluronidase (HYAL)-1/-2 downregulation. Consistent with the recovery of collagen composition, the expression of Pro-COL1A1 was increased by hydrangenol. Matrix metalloproteinase (MMP)-1/-3, cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) expression was reduced by hydrangenol. Hydrangenol attenuated the phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK and p38, activator protein 1 (AP-1) subunit, and signal transduction and activation of transcription 1 (STAT1). Hydrangenol upregulated the expression of nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO-1), glutamate cysteine ligase modifier subunit (GCLM), and glutamate cysteine ligase catalysis subunit (GCLC). Taken together, our data suggest that hydrangenol can prevent wrinkle formation by reducing MMP and inflammatory cytokine levels and increasing the expression of moisturizing factors and antioxidant genes.

Keywords: AP-1; MAPK; MMPs; collagen; hydrangenol; photoaging; skin moisture; ultraviolet B; wrinkle formation.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Cytokines / metabolism
  • Dermatologic Agents / isolation & purification
  • Dermatologic Agents / pharmacology*
  • Hydrangea / chemistry*
  • Inflammation Mediators / metabolism
  • Isocoumarins / isolation & purification
  • Isocoumarins / pharmacology*
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Mice, Hairless
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Proteolysis
  • Signal Transduction
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Skin Aging / drug effects*
  • Skin Aging / radiation effects
  • Ultraviolet Rays / adverse effects*
  • Water / metabolism*


  • Antioxidants
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Cytokines
  • Dermatologic Agents
  • Inflammation Mediators
  • Isocoumarins
  • Plant Extracts
  • Water
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse
  • Matrix Metalloproteinase 3
  • Mmp3 protein, mouse
  • hydrangenol