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      Attenuation of UVB-Induced Photo-Aging by Polyphenolic-Rich Spatholobus Suberectus Stem Extract Via Modulation of MAPK/AP-1/MMPs Signaling in Human Keratinocytes

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          Abstract

          It is well known that ultraviolet light activates mitogen-activated protein (MAP) kinase by increasing the reactive oxygen species (ROS) in the body, enhancing activating protein 1(AP-1) complexes (c-Jun and c-Fos), increasing matrix metalloproteinases (MMPs) and degrading collagen and elastin. In this study, we confirmed that polyphenolic rich Spatholobus suberectus (SS) stem extracts suppressed ultraviolet (UV)-induced photo-aging. The major active components of SS stem extracts were identified as gallic acid, catechin, vanillic acid, syringic acid and epicatechin. The aqueous and ethanolic extracts of the stem of SS (SSW and SSE, respectively) significantly reduced the elastase enzyme activity. Moreover, both extracts were suppressed the ROS generation and cellular damage induced by UVB in HaCaT cells. Our results also revealed that SSE could regulate the expression of MMPs, tissue inhibitor of matrix metalloproteinase (TIMP)-1, collagen type I alpha 1 (COL1A1), elastin (ELN) and hyaluronan synthase 2 (HAS2) at their transcriptional and translational level. Furthermore, SSE was blocked the UVB-induced phosphorylation of mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-κB) and c-Jun. Moreover, combination of syringic acid, epicatechin and vanillic acid showed strong synergistic effects on elastase inhibition activity, in which the combination index (CI) was 0.28. Overall, these results strongly suggest that the polyphenolics of SSE exert anti-ageing potential as a natural biomaterial to inhibit UVB-induced photo-aging.

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          Most cited references34

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          Matrix metalloproteinases and their inhibitors in connective tissue remodeling.

          Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.
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            Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin.

            Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
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              Role of matrix metalloproteinases in renal pathophysiologies.

              Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                14 June 2019
                June 2019
                : 11
                : 6
                : 1341
                Affiliations
                [1 ]Department of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea; rbfl0116@ 123456knu.ac.kr (K.-R.K.); mbalam@ 123456knu.ac.kr (M.B.A.); wlgus6744@ 123456knu.ac.kr (J.-H.P.)
                [2 ]Food and Bio-Industry Research Institute, Inner Beauty/Anti-ageing Center, Kyungpook National University, Daegu 41566, Korea
                [3 ]Biomedical Research Institute, Kyungpook National University Hospital, Daegu 41944, Korea; kimth0929@ 123456ynu.ac.kr
                Author notes
                [* ]Correspondence: sang@ 123456knu.ac.kr ; Tel.: +82-53-950-7754
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8509-6827
                https://orcid.org/0000-0002-2343-7315
                Article
                nutrients-11-01341
                10.3390/nu11061341
                6627339
                31207929
                c913398d-5b58-4be6-bdbf-672ed7608da5
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 April 2019
                : 07 June 2019
                Categories
                Article

                Nutrition & Dietetics
                anti-aging,spatholobus suberectus,matrix metalloproteinases (mmps),collagen type i alpha 1 (col1a1),elastin (eln),mitogen-activated protein kinase (mapk)

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