Thonthula Sreelatha, Sousa Sandra De, Dubuis Alexis, Boudah Samia, Mehta Richa, Singh Akanksha, Eilstein Joan, Tabet Jean-Claude, John Sherluck, Roy Dhimoy, Pannakal Steve Thomas
L'Oréal Research and Innovation, Bangalore 560067, India.
L'Oréal Research and Innovation, 93600 Aulnay-Sous-Bois, France.
Int J Mol Sci. 2024 Nov 27;25(23):12770. doi: 10.3390/ijms252312770.
The skin hydration level is a key factor that influences the physical and mechanical properties of the skin. The stratum corneum (SC), the outermost layer of the epidermis, is responsible for the skin's barrier function. In this study, we investigated the role of a unique composition of extract for its ability to activate CD44, a cell-surface receptor of hyaluronic acid, and aquaporin-3, a water-transporting protein, in human keratinocytes (HaCaT). An ELISA assay evaluating the protein expression levels of CD44, aquaporin-3 (AQP3), filaggrin, and keratin-10 revealed that extract upregulated the levels of CD44 and AQP3 by 15% and 78%, respectively. Additionally, extract demonstrated a comparative effect on water vapor flux in TEWL and lipid perturbation in DSC versus the reference, glycerin. In light of this new biological efficacy, a detailed phytochemical characterization was undertaken using an integrated LC-HRMS/MS-based metabolomics approach, which provided further insights on the chemistry of . This led to the identification of 29 secondary metabolites, 14 of which are reported here for the first time, including esculetin, aesculin, apigenin and kaempferol C-glycosides, megastigmane glycosides, roseoside, platanionoside B, and an eriojaposide B isomer, along with the rare, calenduloside F and esculetin diglucoside, which are reported for the first time from the genus, . Notably, two active components identified in the extract, namely, aesculin and schaftoside, showed an upregulation of the protein expression of CD44 in HaCaT cells by 123% and 193% within 24 h of treatment, respectively, while aesculin increased AQP3 levels by 46%. Aesculin and schaftoside also significantly upregulated the expression of K-10 levels by 299% and 116%, which was considerably higher than sodium hyaluronate, the positive control. The rationale used to characterize the new structures is outlined along with the related biosynthetic pathways envisioned to generate roseoside and Eriojaposide B. These findings provide new molecular insights to deepen the understanding of how extract, along with the biomarkers aesculin and schaftoside, restores the skin barrier and skin hydration benefits.
皮肤水合水平是影响皮肤物理和机械性能的关键因素。角质层（SC）是表皮的最外层，负责皮肤的屏障功能。在本研究中，我们研究了一种独特提取物组合物在人角质形成细胞（HaCaT）中激活透明质酸的细胞表面受体CD44和水转运蛋白水通道蛋白-3的能力所起的作用。一项评估CD44、水通道蛋白-3（AQP3）、丝聚合蛋白和角蛋白-10蛋白表达水平的ELISA分析表明，提取物分别使CD44和AQP3的水平上调了15%和78%。此外，与参考物甘油相比，提取物在经表皮水分流失（TEWL）中的水蒸气通量和差示扫描量热法（DSC）中的脂质扰动方面表现出类似的效果。鉴于这种新的生物学功效，我们采用基于液相色谱-高分辨质谱/质谱的综合代谢组学方法进行了详细的植物化学表征，这为该提取物的化学性质提供了进一步的见解。这导致鉴定出29种次生代谢产物，其中14种在此首次报道，包括七叶亭、七叶苷、芹菜素和山奈酚C-糖苷、大牻牛儿烯糖苷、玫瑰糖苷、悬铃木苷B和一种毛蕊花糖苷B异构体，以及罕见的金盏花苷F和七叶亭二葡萄糖苷，它们首次从该属中报道。值得注意的是，在提取物中鉴定出的两种活性成分，即七叶苷和schaftoside，在处理24小时内分别使HaCaT细胞中CD44的蛋白表达上调了123%和193%，而七叶苷使AQP3水平提高了46%。七叶苷和schaftoside还分别使K-10水平的表达显著上调了299%和116%，这大大高于阳性对照透明质酸钠。阐述了用于表征新结构的基本原理以及设想生成玫瑰糖苷和毛蕊花糖苷B的相关生物合成途径。这些发现提供了新的分子见解，以加深对提取物以及生物标志物七叶苷和schaftoside如何恢复皮肤屏障和皮肤水合益处的理解。
