Rubus idaeus L. (red raspberry) blocks UVB-induced MMP production and promotes type I procollagen synthesis via inhibition of MAPK/AP-1, NF-κβ and stimulation of TGF-β/Smad, Nrf2 in normal human dermal fibroblasts

J Photochem Photobiol B. 2018 Aug:185:241-253. doi: 10.1016/j.jphotobiol.2018.06.007. Epub 2018 Jun 22.

Abstract

Chronic exposure to ultraviolet (UV) radiation causes photo-oxidation, which in turn results in the upregulation of matrix metalloproteinases (MMPs) and loss of collagen. Rubus idaeus L. (RI), also called red raspberry, is an important cash crop that contains abundant antioxidant compounds. Sanguiin H-6 and lambertianin C are the major ingredients presented in the extracts. Here, we studied the protective effect of RI on UVB-induced photoaging in normal human dermal fibroblasts (NHDFs). We found that RI notably reduced UVB-induced MMPs secretion and pro-inflammatory mediators production, and significantly suppressed UVB-induced activation of mitogen-activated protein kinase (MAPK), nuclear factor-κβ, as well as activator protein 1. Additionally, treatment of NHDFs with the ERK inhibitor (PD98059) and JNK inhibitor (SP600125) resulted in the reduction of UVB-induced MMP-1 and IL-6 expressions, which demonstrated that the inhibition of MMP-1 and IL-6 by RI is associated with the MAPK pathway. Furthermore, we also found that RI accelerated procollagen type I synthesis by activating the transforming growth factor-β/Smad pathway and enhanced the expression of cytoprotective antioxidants such as heme oxygenase-1 and NHD(P)H quinone oxidoreductase 1 by promoting nuclear factor E2-related factor 2 nuclear transfer. Overall, these findings demonstrated that RI was potentially effective in preventing UVB induced skin photoaging.

Keywords: Matrix metalloproteinase; Normal human dermal fibroblasts; Rubus idaeus L; Type I procollagen; Ultraviolet B.

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Collagen Type I / metabolism*
  • Dermis / cytology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rubus / chemistry*
  • Rubus / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / radiation effects
  • Smad Proteins / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transforming Growth Factor beta / metabolism
  • Ultraviolet Rays*

Substances

  • Antioxidants
  • Collagen Type I
  • Interleukin-6
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Phenols
  • Plant Extracts
  • Smad Proteins
  • Transcription Factor AP-1
  • Transforming Growth Factor beta
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases