Research & Development Division, Oryza Oil & Fat Chemical Co., Ltd., Aichi, Japan.
Research Institute for Biological Functions, Chubu University, Aichi, Japan.
PLoS One. 2018 Oct 9;13(10):e0205061. doi: 10.1371/journal.pone.0205061. eCollection 2018.
The activation of peroxisomeproliferator-activated receptor (PPAR) α can stimulate the expression of ceramide-related enzymes, and a major component of strawberry seed extract (SSE) tiliroside enhances the expression of PPARα. We determined whether SSE and tiliroside may stimulate ceramide synthesis in the stratum corneum (SC) of the human epidermal equivalents (HEEs) culture model. Treatment with SSE at 1.0 and 3.0 μg/mL elicited a significant increase in the total ceramide content in the SC, which was accompanied by a significant increase in almost all ceramide species except for ceramide [EOS] and [AP]. Treatment with tiliroside at 0.3 μg/mL slightly accentuated the total ceramide content in the SC together with a significant increase in the ceramide [NS, NDS] content. Messenger RNA analysis demonstrated that SSE at 1 or 3 μg/mL significantly stimulated the gene expression of serine palmitoyltransferase (SPT) 2, ceramide synthase (CerS) 3, glucosylceramide synthase (GCS), and β-glucocerebrosidase (GBA) but not of SPT1, sphingomyelin synthase (SMS) 1/2 and acid sphingomyelinase (ASM). In contrast, tiliroside elicited significant increases in the gene expression levels of GCS and GBA only at 0.3 and/or 0.1 μg/mL. Western blotting analysis revealed that both SSE and tiliroside enhanced the protein expression levels of GCS and GBA but not of SPT2 at 1 or 3 and 0.1 or 0.3 μg/mL, respectively. These findings suggested that both SSE and tiliroside have a distinct potential to stimulate the level of ceramide [NS, NDS] in the SC by enhancing the expression of GCS and GBA. The higher stimulatory effect with SSE than tiliroside on SC ceramide synthesis correlates with the significant increase observed with SSE but not tiliroside in the gene expression levels of SPT2 and CerS3. Therefore, it is anticipated that SSE is effective in improving skin barrier function and moisture retention in several ceramide-deficit skin conditions, including surfactant-induced roughened skin, xerosis, and atopic dermatitis.
过氧化物酶体增殖物激活受体 (PPAR)α 的激活可以刺激神经酰胺相关酶的表达,而草莓种子提取物 (SSE) 中的主要成分虎杖苷可以增强 PPARα 的表达。我们确定 SSE 和虎杖苷是否可能刺激人表皮等效物 (HEE) 培养模型角质层 (SC) 中的神经酰胺合成。用 1.0 和 3.0μg/mL 的 SSE 处理可显著增加 SC 中的总神经酰胺含量,同时除神经酰胺 [EOS] 和 [AP] 外,几乎所有神经酰胺种类的含量都显著增加。用 0.3μg/mL 的虎杖苷处理可略微增加 SC 中的总神经酰胺含量,同时神经酰胺 [NS,NDS] 的含量显著增加。信使 RNA 分析表明,SSE 以 1 或 3μg/mL 显著刺激丝氨酸棕榈酰转移酶 (SPT)2、神经酰胺合酶 (CerS)3、葡萄糖神经酰胺合酶 (GCS) 和 β-葡萄糖脑苷脂酶 (GBA) 的基因表达,但 SPT1、神经酰胺合成酶 (SMS)1/2 和酸性神经酰胺酶 (ASM) 的基因表达不显著。相反,虎杖苷仅在 0.3 和/或 0.1μg/mL 时引起 GCS 和 GBA 的基因表达水平显著增加。Western blot 分析表明,SSE 和虎杖苷均增强了 GCS 和 GBA 的蛋白表达水平,但 SPT2 的蛋白表达水平没有增强,分别在 1 或 3 和 0.1 或 0.3μg/mL。这些发现表明,SSE 和虎杖苷均通过增强 GCS 和 GBA 的表达,具有刺激 SC 中神经酰胺 [NS,NDS] 水平的独特潜力。SSE 对 SC 神经酰胺合成的刺激作用强于虎杖苷,这与 SSE 而非虎杖苷显著增加 SPT2 和 CerS3 的基因表达水平有关。因此,预计 SSE 可有效改善几种神经酰胺缺乏皮肤状况(包括表面活性剂引起的粗糙皮肤、干燥和特应性皮炎)的皮肤屏障功能和保水能力。