AVR Consulting Ltd., Northwich, UK.
DSM Nutritional Products Ltd., Kaiseraugst, Switzerland.
Int J Cosmet Sci. 2021 Oct;43(5):619-626. doi: 10.1111/ics.12730. Epub 2021 Sep 5.
We report on the in vitro and ex vivo effects of chiral (R)-10-hydroxystearic acid (10-HSA) compared with other mono-hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol.
Following treatment with hydroxystearic acids peroxisomal proliferator-activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast collagen proteome was studied by mass-spectrometry-based proteomics and collagen type III was assessed by immunohistochemistry on human ex vivo skin.
10-HSA was the most effective PPARα agonist (15.7× induction; p < 0.001), followed by 9-HSA (10.1× induction) and then 12-HSA (4.9× induction) with 17-HSA (1.7× induction) being similar to the effects of stearic acid (1.8× induction). Collagen type I levels were increased in primary human fibroblasts by 2.12× and 1.56× for 10-HSA and 9-HSA, respectively, in vitro with the10-HSA being significant (p < 0.05), whereas 12-HSA and SA had no statistical effect over the untreated control. 10-HSA and 12-HSA modified the intracellular fibroblast collagen proteome slightly with significant increases in collagen alpha-1 (VI) and alpha-3 (VI) proteins but only 10-HSA increased levels of collagen alpha-2 (V), alpha-1 (III), alpha-1 (I) and alpha-2 (I) (all p < 0.05) with the increases being significantly different between 10-HSA and 12-HSA for collagen alpha-1 (I), collagen-3 (VI) and collagen alpha-2 (I) (p < 0.01). Collagen type III in ex vivo skin was increased +47% (p < 0.05) by 0.05% (1.7 mM) retinol, +70% (p < 0.01) by 0.01% (0.33 mM) 10-HSA and the combination increased levels by +240% (p < 0.01 for either ingredient).
Chiral (R)-10-HSA has been shown to be superior to 9, 12 and 17-HSA as a PPARα agonist. Moreover, 10-HSA stimulated collagen synthesis in monolayer fibroblast culture as assessed by proteomics and immunohistochemically. Furthermore, we also show the synergistic effects of 10-HSA with retinol on collagen III synthesis in skin explants. These results further highlight the efficacy of 10-HSA as a cosmetically acceptable PPARα agonist and anti-ageing ingredient.
我们报告了手性（R）-10-羟基硬脂酸（10-HSA）与其他单羟基硬脂酸区域异构体和硬脂酸（SA）以及与视黄醇联合使用的体外和离体效果。
用羟硬脂酸处理后，通过荧光素酶报告基因测定法测定过氧化物酶体增殖物激活受体α（PPARα）的活性，用免疫组织化学法测定原代人真皮成纤维细胞中的 I 型胶原，通过基于质谱的蛋白质组学研究细胞内成纤维胶原蛋白质组的修饰，并用免疫组织化学法评估人离体皮肤中的 III 型胶原。
10-HSA 是最有效的 PPARα 激动剂（诱导 15.7 倍；p < 0.001），其次是 9-HSA（诱导 10.1 倍），然后是 12-HSA（诱导 4.9 倍），17-HSA（诱导 1.7 倍）与硬脂酸的效果相似（诱导 1.8 倍）。10-HSA 和 9-HSA 在体外分别使原代人成纤维细胞中的 I 型胶原水平增加了 2.12 倍和 1.56 倍，10-HSA 具有统计学意义（p < 0.05），而 12-HSA 和 SA 对未经处理的对照组没有统计学影响。10-HSA 和 12-HSA 略微改变了细胞内成纤维胶原蛋白质组，使胶原 alpha-1（VI）和 alpha-3（VI）蛋白显著增加，但只有 10-HSA 增加了 alpha-2（V）、alpha-1（III）、alpha-1（I）和 alpha-2（I）的水平（均 p < 0.05），10-HSA 和 12-HSA 之间在 alpha-1（I）、collagen-3（VI）和 alpha-2（I）的胶原水平上存在显著差异（p < 0.01）。在离体皮肤中，0.05%（1.7 mM）视黄醇增加了 III 型胶原的水平+47%（p < 0.05），0.01%（0.33 mM）10-HSA 增加了+70%（p < 0.01），联合使用增加了+240%（p < 0.01）。
手性（R）-10-HSA 已被证明是比 9、12 和 17-HSA 更好的 PPARα 激动剂。此外，10-HSA 通过蛋白质组学和免疫组织化学法刺激单层成纤维细胞培养中的胶原合成。此外，我们还显示了 10-HSA 与视黄醇在皮肤外植体中 III 型胶原合成方面的协同作用。这些结果进一步强调了 10-HSA 作为一种可接受的美容用 PPARα 激动剂和抗衰老成分的功效。
