Effects of Macelignan Isolated from <i>Myristica fragrans</i> (Nutmeg) on Expression of Matrix Metalloproteinase-1 and Type I Procollagen in UVB-Irradiated Human Skin Fibroblasts

Abstract

Exposure to ultraviolet (UV) light causes premature skin aging that is associated with upregulated matrix metalloproteinases (MMPs) and decreased collagen synthesis. Macelignan, a natural lignan compound isolated from Myristica fragrans HOUTT. (nutmeg), has been reported to possess antioxidant and antiinflammatory activities. This study assessed the effects of macelignan on photoaging and investigated its mechanisms of action in UV-irradiated human skin fibroblasts (Hs68) by reverse transcription-polymerase chain reaction, Western blot analysis, 2′,7′-dichlorofluorescein diacetate assay, and enzyme-linked immunosorbent assay. Our results show that macelignan attenuated UV-induced MMP-1 expression by suppressing phosphorylation of mitogen-activated protein kinases (MAPKs) induced by reactive oxygen species. Macelignan also increased type I procollagen expression and secretion through transforming growth factor β (TGF-β)/Smad signaling. These findings indicate that macelignan regulates the expression of MMP-1 and type I procollagen in UV-irradiated human skin fibroblasts by modulating MAPK and TGF-β/Smad signaling, suggesting its potential as an efficacious antiphotoaging agent.Key words macelignan; matrix metalloproteinase-1; type I procollagen; mitogen-activated protein kinase; UV irradiation; reactive oxygen species Skin aging, which causes wrinkling, sagging and roughness, can be divided into two distinct processes: intrinsic aging and photoaging. Photodamage and premature skin aging is caused by ultraviolet (UV) irradiation, which increases the synthesis of matrix metalloproteinases (MMPs).1) MMP upregulation in skin fibroblasts accelerates the degradation of dermal collagen, which confers tensile strength.2) Skin aging is characterized by reductions in type I collagen, the primary component of the extracellular matrix (ECM), which provides structural support to the skin dermis.3) Therefore, natural compounds that decrease the MMP production and increase procollagen synthesis may have potential for the prevention and treatment of photoaging. Most are secreted as inactive proenzymes (proMMPs) that are activated primarily by proteolytic cascades, generally catalyzed by neutral proteinases. MMP-1 is primarily responsible for degradation of ECM. 4)UV irradiation also leads to the generation of reactive oxygen species (ROS), direct or indirect DNA damage, and inflammatory response and damage to ECM integrity. 5)

Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg (Myristica fragrans Houtt.)

“…The use of macelignan as an antiphotoaging agent stems from its antioxidant, antionflammtory, as well as its documented ability to protect human skin fibroblasts against damaging effects of UVB irradiation. The observed protective effect is mediated by suppression of two cellular responses involved in premature skin aging: the upregulation of matrix metalloproteinases (MMPs) and reduced collagen synthesis (Lee et al 2012). Another potential skin application for macelignan was reported by Choi et al whereby the authors suggested the use of macelignan as a natural depigmenting agent based on its ability, at 10 M concentration, to inhibit melanosome transfer and dendrite formation in B16F10 melanoma cells (Choi et al 2011).…”

Ganoderma lucidum polysaccharides protect fibroblasts against UVB-induced photoaging

“…Previous studies have demonstrated the positive effects of herbal extracts in preventing skin photoaging: Sun et al (21) revealed that wild chrysanthemum extract downregulates ROS levels within HaCat cells and so reduces MMP-2 and MMP-9 expression by inhibiting UV-induced ERK1/2 and p38 phosphorylation to prevent UVB-related acute skin damage and photoaging. Lee et al (22) demonstrated that macelignan, an effective antioxidant found in the nutmeg, Myristica fragans , downregulates MMP-1 expression by reducing UV exposure-related ROS elevation and MAPK phosphorylation. In addition, it increases type I collagen expression by activating transforming growth factor β (TGF-β)/SMAD signaling to effectively prevent and treat skin photoaging.…”

Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice

“…UV irradiation induced protein expression of the AP-1 family members, c-Jun and c-Fos (Quan et al, 2005). Type I procollagen and elastin are elastic proteins that participate in organizational flexibility and elasticity (Lee et al, 2012;Zheng et al, 2012;Fan et al, 2013;Hwang et al, 2011;Devy et al, 2010). Transforming growth factor beta (TGF-β) is a protein that is involved with identity, function, and survival in cells.…”