Many traditional Chinese medicines (TCMs) with skin-whitening properties have been recorded in the Ben-Cao-Gang-Mu and in folk prescriptions, and some literature confirms that their extracts do have the potential to inhibit pigmentation. However, no systematic studies have identified the specific regulatory mechanisms of the potential active ingredients. The aim of this study was to screen the ingredients in TCMs that inhibit skin pigmentation through a network pharmacology system and to explore underlying mechanisms. We identified 148 potential active ingredients from 14 TCMs, and based on the average “degree” of the topological parameters, the top five TCMs (Fructus Ligustri Lucidi, Hedysarum multijugum Maxim., Ampelopsis japonica, Pseudobulbus Cremastrae Seu Pleiones, and Paeoniae Radix Alba) that were most likely to cause skin-whitening through anti-inflammatory processes were selected. Sitogluside, the most common ingredient in the top five TCMs, inhibits melanogenesis in human melanoma cells (MNT1) and murine melanoma cells (B16F0) and decreases skin pigmentation in zebrafish. Furthermore, mechanistic research revealed that sitogluside is capable of downregulating tyrosinase (TYR) expression by inhibiting the ERK and p38 pathways and inhibiting TYR activity. These results demonstrate that network pharmacology is an effective tool for the discovery of natural compounds with skin-whitening properties and determination of their possible mechanisms. Sitogluside is a novel skin-whitening active ingredient with dual regulatory effects that inhibit TYR expression and activity.

中文翻译：

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通过网络药理学鉴定西托格鲁苷作为潜在的皮肤色素沉着减少剂

《本草纲目》和民间方剂中记载了许多具有美白功效的中药，一些文献证实其提取物确实具有抑制色素沉着的潜力。然而，尚无系统研究确定潜在活性成分的具体调控机制。本研究旨在通过网络药理学系统筛选抑制皮肤色素沉着的中药成分，并探索其潜在机制。我们从 14 种中药中鉴定出 148 种潜在活性成分，根据拓扑参数的平均“度数”，排名前 5 的中药（女贞子、黄花菜、蛇尾草）, Pseudobulbus Cremastrae Seu Pleiones和Paeoniae Radix Alba) 选择了最有可能通过抗炎过程引起皮肤美白的物质。Sitogluside 是前五种中药中最常见的成分，可抑制人黑色素瘤细胞 (MNT1) 和鼠黑色素瘤细胞 (B16F0) 的黑色素生成，并减少斑马鱼的皮肤色素沉着。此外，机理研究表明，西格鲁苷能够通过抑制 ERK 和 p38 通路并抑制 TYR 活性来下调酪氨酸酶 (TYR) 的表达。这些结果表明，网络药理学是发现具有皮肤美白特性的天然化合物并确定其可能机制的有效工具。Sitogluside 是一种新型的美白活性成分，具有抑制 TYR 表达和活性的双重调节作用。