Nu Skin Enterprises, Personal Care Products Division, Provo, Utah 84604, USA.
Biofactors. 2012 Jan-Feb;38(1):44-52. doi: 10.1002/biof.191. Epub 2012 Jan 27.
The purpose of this study was to investigate the effects of equol, a plant and intestinal flora derived isoflavonoid molecule on the expression of skin genes and proteins using human dermal models. As equol has been shown to mimic 17β-estradiol and bind specifically to 5α-dihydrotestostone (5α-DHT), these agents were used (in addition to equol) to determine whether equol may play important and beneficial roles in the extracellular matrix (ECM). Equol at 0.3 or 1.2% in qPCR experiments using a human skin barrier model examined ECM gene expression. Equol, 5α-DHT, and 17β-estradiol at 10 nM were studied in human monolayer fibroblasts cultures (hMFC) for ECM protein expression. Human fibroblast three-dimensional organotypic cultures revealed equol's influence (@ 10 nM) on ECM proteins via fluorescent-activated cell sorting (FACS) analysis. In qPCR experiments, equol significantly increased collagen, elastin (ELN), and tissue inhibitor of metalloprotease and decreased metalloproteinases (MMPs) gene expression and caused significant positive changes in skin antioxidant and antiaging genes. In hMFC, equol significantly increased collagen type I (COL1A1), whereas, 5α-DHT significantly decreased cell viability that was blocked by equol. FACS analysis showed equol and 17β-estradiol significantly stimulated COL1A1, collagen type III (COL3A1), and ELN while MMPs were significantly decreased compared with control values. Finally, tamoxifen blocked the positive influences of equol on ECM proteins via FACS analysis. These findings suggest that equol has the potential to be used topically for the treatment and prevention of skin aging, by enhancing ECM components in human skin.
本研究旨在探讨植物和肠道菌群衍生的异黄酮分子雌马酚对人皮肤模型中皮肤基因和蛋白表达的影响。由于雌马酚已被证明能模拟 17β-雌二醇并特异性结合 5α-二氢睾酮(5α-DHT),因此我们使用了这些物质(除了雌马酚之外),以确定雌马酚是否可能在细胞外基质(ECM)中发挥重要且有益的作用。在使用人皮肤屏障模型的 qPCR 实验中,我们检测了 0.3%或 1.2%的雌马酚对 ECM 基因表达的影响。在人单层成纤维细胞培养物(hMFC)中,研究了 10 nM 的雌马酚、5α-DHT 和 17β-雌二醇对 ECM 蛋白表达的影响。人成纤维细胞三维器官培养物通过荧光激活细胞分选(FACS)分析揭示了雌马酚(@10 nM)对 ECM 蛋白的影响。在 qPCR 实验中,雌马酚显著增加了胶原蛋白、弹性蛋白(ELN)和组织金属蛋白酶抑制剂,减少了金属蛋白酶(MMPs)的基因表达,并导致皮肤抗氧化和抗衰老基因的显著正向变化。在 hMFC 中,雌马酚显著增加了胶原蛋白 I(COL1A1),而 5α-DHT 则显著降低了细胞活力,而雌马酚则阻断了这一作用。FACS 分析表明,与对照值相比,雌马酚和 17β-雌二醇显著刺激了 COL1A1、胶原蛋白 III(COL3A1)和 ELN 的表达,同时 MMPs 的表达显著降低。最后,通过 FACS 分析,他莫昔芬阻断了雌马酚对 ECM 蛋白的正向影响。这些发现表明,雌马酚有可能通过增强人皮肤中的 ECM 成分,用于皮肤衰老的治疗和预防。