Iwahashi Hiroyasu, Kawashima Yoshihito, Masaki Hitoshi, Taga Atsushi
Research Center, Maruzen Pharmaceuticals Co., Ltd., Hiroshima, Japan.
Laboratory of Photoaging Research, School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
Photodermatol Photoimmunol Photomed. 2025 Mar;41(2):e70006. doi: 10.1111/phpp.70006.
The collagen receptor Endo180 participates in extracellular matrix remodeling by clearing the pericellular environment and recognizing and internalizing collagen degradation products. In photoaged skin, Endo180 expression in fibroblasts is decreased, and collagen fragments accumulate in the pericellular environment, leading to a decrease in type I collagen production and an increase in matrix metalloproteinase 1 production. This suggests that a decrease in Endo180 production may promote wrinkle formation by decreasing the dermal collagen fibril volume. Therefore, this study aimed to identify materials that promote Endo180 production in vitro and investigate whether promoting Endo180 production could prevent and improve wrinkles in vivo.
Endo180 gene expression and protein production in fibroblasts were evaluated after screening 71 natural extracts. The conditioned medium of UVB-irradiated keratinocytes and Endo180 production-promoting extract were added to fibroblasts, and Endo180 and type I collagen production were evaluated. In a double-blind, randomized, placebo-controlled study, a cream formulated with an Endo180 production-promoting extract or placebo was topically administered to each side of the face of 20 healthy women twice daily for 8 weeks.
Screening results showed that 50 μg/mL of lemon balm (Melissa officinalis L.) leaf extract (MOLE) resulted in the highest levels of both Endo180 mRNA and protein at 178.1% and 127.4%, respectively. Its major component rosmarinic acid also promoted Endo180 production by 143.9% at a concentration of 20 μg/mL. MOLE at 200 μg/mL almost completely inhibited the decrease in Endo180 and type I collagen production in UVB-irradiated keratinocyte-conditioned medium. Furthermore, eye-corner wrinkles were reduced by treatment with the MOLE formulation compared to that in response to the placebo formulation.
MOLE may act as an antiwrinkle agent that inhibits the decline in collagen levels by promoting Endo180 production.
胶原蛋白受体Endo180通过清除细胞周围环境以及识别和内化胶原蛋白降解产物参与细胞外基质重塑。在光老化皮肤中,成纤维细胞中Endo180的表达降低,胶原蛋白片段在细胞周围环境中积累,导致I型胶原蛋白生成减少,基质金属蛋白酶1生成增加。这表明Endo180生成减少可能通过降低真皮胶原纤维体积促进皱纹形成。因此,本研究旨在体外鉴定能促进Endo180生成的物质,并研究促进Endo180生成是否能在体内预防和改善皱纹。
在筛选71种天然提取物后,评估成纤维细胞中Endo180基因表达和蛋白质生成。将紫外线B照射的角质形成细胞的条件培养基和促进Endo180生成的提取物添加到成纤维细胞中,评估Endo180和I型胶原蛋白生成。在一项双盲、随机、安慰剂对照研究中,将含有促进Endo180生成提取物或安慰剂的乳膏每天两次局部涂抹于20名健康女性面部两侧,持续8周。
筛选结果显示,50μg/mL的香蜂花叶提取物(MOLE)使Endo180 mRNA和蛋白质水平分别达到最高,分别为178.1%和127.4%。其主要成分迷迭香酸在浓度为20μg/mL时也使Endo180生成增加了143.9%。200μg/mL的MOLE几乎完全抑制了紫外线B照射的角质形成细胞条件培养基中Endo180和I型胶原蛋白生成的减少。此外,与安慰剂制剂相比,MOLE制剂治疗可减少眼角皱纹。
MOLE可能作为一种抗皱剂,通过促进Endo180生成来抑制胶原蛋白水平下降。