Protective effect of dietary Alchemilla mollis on UVB-irradiated premature skin aging through regulation of transcription factor NFATc1 and Nrf2/ARE pathways

Phytomedicine. 2018 Jan 15;39:125-136. doi: 10.1016/j.phymed.2017.12.025. Epub 2017 Dec 26.


Background: Alchemilla mollis (lady's mantle) is a common ingredient in skin care products. However, the protective mechanism of A. mollis against skin problems has not been elucidated.

Purpose: This study was to investigate the effects of A. mollis ethanolic extract (AM) on UVB-irradiated normal human dermal fibroblasts (NHDF) and hairless mice.

Methods: The in vitro anti-photoaging effect of AM was performed in NHDFs. The antioxidant activities were assessed through DPPH, ABTS, and reactive oxygen species (ROS) assays. Matrix metalloproteinase 1 (MMP-1), IL-6, procollagen type I, and transforming growth factor-β1 (TGF-β1) were measured by kits. The protein levels of p-c-Jun, p-c-Fos, Nrf2, NQO-1, HO-1, nuclear NFATc1 and cytosolic p-NFATc1 were evaluated by western blotting. In in vivo, H&E and Masson's trichrome staining were carried out. Skin texture was analyzed using the roughness parameters. The expression of MMP-1, procollagen type I, TGF-β1 and elastin were measured by western blot.

Results: AM included gallic acid as an active constituent. AM exhibited a strong antioxidant effect by inhibiting DPPH and ABTS free radicals, as well as ROS production. It was also found to upregulate transforming growth factor β1, type I procollagen and elastin expression, and to downregulate matrix metalloproteinase-1 and interleukin-6 expression in AM-treated NHDFs under UVB irradiation. These effects were attributed to AP-1 and Nrf2/ARE signaling pathways. Significantly, it was demonstrated that AM regulated the UVB-induced NFATc1 dephosphorylation in nucleus. Based on dietary data, AM was effective for the prevention of wrinkle formation, skin thickening, water loss, and erythema in UVB-exposed mouse skin.

Conclusion: Our data indicate that A. mollis provides protection from UVB exposure in both hairless mice skin in vivo and NHDFs in vitro. AM might therefore be useful as a cosmetic material and functional food for the prevention of UVB-induced human skin photoaging.

Keywords: Alchemilla mollis; Anti-aging; NFATc1; Nrf2/ARE; Skin; UVB.

MeSH terms

  • Alchemilla / chemistry*
  • Animals
  • Antioxidant Response Elements / drug effects
  • Antioxidants / pharmacology*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Dietary Supplements
  • Fibroblasts / drug effects
  • Fibroblasts / radiation effects
  • Gallic Acid / analysis
  • Humans
  • Male
  • Mice, Hairless
  • NF-E2-Related Factor 2 / metabolism
  • NFATC Transcription Factors / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Skin Aging / drug effects*
  • Skin Aging / radiation effects
  • Ultraviolet Rays / adverse effects


  • Antioxidants
  • Collagen Type I
  • NF-E2-Related Factor 2
  • NFATC Transcription Factors
  • NFE2L2 protein, human
  • Plant Extracts
  • Reactive Oxygen Species
  • Gallic Acid