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

• Published in: Phytomedicine (Stuttgart) 2018-01, Vol.39, p.125-136
• Main Authors: Hwang, Eunson, Ngo, Hien T.T., Seo, Seul A, Park, Bom, Zhang, Mengyang, Yi, Tae-Hoo
• Format: Article
• Language: English
• Subjects: Alchemilla - chemistry; Alchemilla mollis; Animals; Anti-aging; 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; NFATc1; Nrf2/ARE; Plant Extracts - chemistry; Plant Extracts - pharmacology; Reactive Oxygen Species - metabolism; Skin; Skin Aging - drug effects; Skin Aging - radiation effects; Ultraviolet Rays - adverse effects; UVB
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.12.025

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