Kubo Hirokazu, Moriyama Mariko, Goto Saya, Miyake Yuko, Nakamura Maki, Ozeki Yuki, Nakamura Yukio, Moriyama Hiroyuki
R&D Headquarters, KOBAYASHI Pharmaceutical Co., Ltd., Ibaraki, Osaka, Japan.
Pharmaceutical Research and Technology Institute, Kindai University, Higashi-Osaka, Osaka, Japan.
PLoS One. 2025 Jun 10;20(6):e0325242. doi: 10.1371/journal.pone.0325242. eCollection 2025.
Salvia officinalis (sage) extract has demonstrated potential as a functional ingredient for skin care application. However, its effect and mechanism in regulating skin pigmentation remain largely unclear. This study investigated the effects of sage ethanol extract (SGE) on melanogenesis and its underlying molecular mechanisms. Treatment with SGE in a human skin equivalent model (3D-skin) suppressed melanin production. To clarify the mechanism of action, the study focused on senescence-associated secretory phenotype (SASP) factors, which are implicated in age-related pigmentation changes. q-PCR and ELISA analyses showed that SGE inhibits melanogenesis by suppressing the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), a known SASP factor in keratinocytes. Interestingly, a similar effect was observed with L-ascorbic acid 2-glucoside (AG), previously identified as a tyrosinase inhibitor. Importantly, p38 and JNK MAP-kinase were identified as upstream regulators of GM-CSF that are suppressed by SGE. These findings provide new insights into how SGE and AG regulate pigmentation via keratinocyte-derived GM-CSF, highlighting their potential in modulating skin tone and pigmentation through cellular signaling pathways.
鼠尾草提取物已显示出作为皮肤护理应用功能成分的潜力。然而，其调节皮肤色素沉着的作用和机制仍不清楚。本研究调查了鼠尾草乙醇提取物（SGE）对黑素生成的影响及其潜在分子机制。在人皮肤等效模型（3D皮肤）中用SGE处理可抑制黑色素生成。为阐明作用机制，该研究聚焦于与衰老相关的分泌表型（SASP）因子，其与年龄相关的色素沉着变化有关。q-PCR和ELISA分析表明，SGE通过抑制角质形成细胞中已知的SASP因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）的表达来抑制黑素生成。有趣的是，之前被鉴定为酪氨酸酶抑制剂的L-抗坏血酸2-葡萄糖苷（AG）也观察到类似效果。重要的是，p38和JNK丝裂原活化蛋白激酶被确定为GM-CSF的上游调节因子，且被SGE抑制。这些发现为SGE和AG如何通过角质形成细胞衍生的GM-CSF调节色素沉着提供了新见解，突出了它们通过细胞信号通路调节肤色和色素沉着的潜力。
