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

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2018-08, Vol.185, p.241-253
• Main Authors: Gao, Wei, Wang, Yu-shuai, Hwang, Eunson, Lin, Pei, Bae, Jahyun, Seo, Seul A., Yan, Zhengfei, Yi, Tae-Hoo
• Format: Article
• Language: English
• Subjects: Activator protein 1; Antioxidants; Antioxidants - chemistry; Antioxidants - metabolism; Berries; Cash crops; Cell Line; Cell Survival - drug effects; Cell Survival - radiation effects; Chronic exposure; Collagen; Collagen Type I - metabolism; Dermis - cytology; Extracellular signal-regulated kinase; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Growth factors; Heme oxygenase (decyclizing); Humans; Inflammation; Inhibition; Inhibitors; Interleukin 6; Interleukin-6 - metabolism; Interstitial collagenase; Kinases; MAP kinase; Matrix metalloproteinase; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Mitogen-Activated Protein Kinases - metabolism; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Normal human dermal fibroblasts; Nuclear transfer; Oxidation; Phenols - chemistry; Phenols - isolation & purification; Phenols - pharmacology; Photooxidation; Plant Extracts - chemistry; Plant Extracts - pharmacology; Procollagen; Protein kinase; Proteins; Quinone oxidoreductase; Quinones; Rubus - chemistry; Rubus - metabolism; Rubus idaeus; Rubus idaeus L; Signal Transduction - drug effects; Signal Transduction - radiation effects; Skin; Smad Proteins - metabolism; Synthesis; Transcription Factor AP-1 - metabolism; Transcription factors; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Type I procollagen; Ultraviolet B; Ultraviolet radiation; Ultraviolet Rays
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2018.06.007

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. Chronic exposure to UV radiation results in skin premature aging (photoaging), clinically accompanied with loss of elasticity and tension. In this study, we demonstrated that RI could reverse this damage via increasing procollagen synthesis and blocking MMPs, inflammatory factors expression. The studies of molecular mechanism indicated RI could inhibit MMPs expression via inactivating MAPK/AP-1, NF-κβ pathway and accelerate type I procollagen synthesis through activating the TGF-β/Smad pathway. Furthermore, RI reduced UVB-enhanced ROS via promoting Nrf2 nuclear location and enhancing the expression of cytoprotective antioxidants. [Display omitted] •RI blocks MMPs and IL-6 secretion by inhibition of MAPK/AP-1 signaling pathway.•RI promotes procollagen type I synthesis by activation of TGF-β/Smad signaling pathway.•RI enhances cytoprotective antioxidants expression by stimulation of Nrf2 nuclear transfer.