Abstract

Reactive oxygen species (ROS) are generated during intrinsic (chronological aging) and extrinsic (photoaging) skin aging. Therefore, antioxidants that inhibit ROS production may be involved in delaying skin aging. In this study, we investigated the potential effects of compounds isolated from black ginger, Kaempferia parviflora, a traditional medicinal plant, on normal human dermal fibroblasts in the context of inflammation and oxidative stress. The isolated compounds were structurally characterized as 5-hydroxy-7-methoxyflavone (1), 3,7-dimethoxy-5-hydroxyflavone (2), 5-hydroxy-3,7,3,4-tetramethoxyflavone (3), 7,4-dimethylapigenin (4), 3,7,4-trimethylkaempferol (5), and 3,5,7-trimethoxyflavone (6), using nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC/MS) analyses. These flavonoids were first evaluated for their ability to suppress extracellular matrix degradation in normal human dermal fibroblasts. Of these, 3,5,7-trimethoxyflavone (6) significantly inhibited the tumor necrosis factor (TNF)-α-induced high expression and secretion of matrix metalloproteinase (MMP)-1 by cells. We further found that 3,5,7-trimethoxyflavone suppressed the excessive increase in ROS, mitogen-activated protein kinases (MAPKs), Akt, and cyclooxygenase-2 (COX-2)and increased heme oxygenase (HO)-1 expression. The expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, was also suppressed by 3,5,7-trimethoxyflavone (6). Taken together, our results indicate that 3,5,7-trimethoxyflavone (6) isolated from K. parviflora is a potential candidate for ameliorating skin damage.

Highlights

  • The skin is a major defensive organ formed from the human ectoderm; it performs sensory, control, and protective functions when in direct contact with latent harmful factors [1]

  • Effect of Flavonoids 1–6 Isolated from K. parviflora on Viability of normal human dermal fibroblasts (NHDFs)

  • We studied the effects of methoxyflavones isolated from black ginger (K. parviflora), including 5-hydroxy-7-methoxyflavone (1), 3,7-dimethoxy-5hydroxyflavone (2), 5-hydroxy-3,7,3,4-tetramethoxyflavone (3), 7,4-dimethylapigenin (4), 3,7,4-trimethylkaempferol (5), and 3,5,7-trimethoxyflavone (6) on tumor necrosis factor (TNF)-α-induced damage to normal human dermal fibroblasts (NHDF) with the measurement of matrix metalloproteinase (MMP)-1 and COLIA1 expression

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Summary

Introduction

The skin is a major defensive organ formed from the human ectoderm; it performs sensory, control, and protective functions when in direct contact with latent harmful factors [1]. Intrinsic aging appears with a gradual decrease in cell activity of skin with age, and is caused by reactive oxygen species (ROS) produced from the cell metabolic process [2,3]. External aging and skin damage occur upon direct exposure to the external environment and are caused by environmental hazards, such as pollution, chemicals, smoking, and ultraviolet (UV) radiation [4,5]. UV radiation substantially contributes to various skin injuries and diseases, including skin aging and inflammatory skin diseases [6,7]. UV radiation induces intracellular ROS formation, causing widespread inflammatory damage from the epidermis to the dermis, resulting in accumulative skin damage, such as skin pigmentation and photoaging [8,9]. ROS generation causes intracellular oxidative damage and changes, 4.0/)

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