Biswas Kazal Boron, Kawai Yuka, Nakagawa Satoshi, Kanai Kyoko, Kojima Hiroyuki, Masutani Teruaki, Oyama Masayoshi, Iddamalgoda Arunasiri, Sakamoto Kotaro
Department of Research and Development, Ichimaru Pharcos Co. Ltd., Motosu, Gifu, Japan.
Laboratory of Pharmacognosy, Gifu Pharmaceutical University, Gifu, Japan.
Sci Rep. 2025 Jan 15;15(1):2042. doi: 10.1038/s41598-025-86320-4.
Hyaluronic acid (HA) is an important component of the skin's extracellular matrix, and its degradation leads to wrinkles. Hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID) is the main factor responsible for HA degradation in dermis. This study aimed to identify natural plant materials that can effectively suppress HYBID expression and protect HA from degradation. Screening of various plant extracts was performed for the inhibition of histamine-induced mRNA expression of HYBID in normal human dermal fibroblasts (NHDF). The molecular size distribution of HA was evaluated by incubating fluorescein isothiocyanate (FITC)-labeled large HA (1200-1600 kDa) in NHDF for certain time followed by measuring different sizes of FITC-labeled HA in the cultured medium by HPLC. Among 380 plant extracts, we found that Artemisia capillaris flower extract (ACFE) was the most effective agent in both suppressing HYBID expression as well as protecting large HA from degradation. Subsequent mechanism elucidation studies showed that ACFE epigenetically regulates the expression of HYBID by modulating the expression of a specific miRNA, miR-486-5p, which is known to directly target and inhibit HYBID expression. Our active compound search identified 1-caffeoyl-3-hydroxybutane and 3-caffeoyl-1-hydroxybutane in ACFE as new compounds, which we named Kawarayomogin I and Kawarayomogin II, respectively. This is the first report to show that Artemisia capillaris with two novel active compounds inhibits HYBID expression as well as hyaluronic acid degradation, and therefore, could be used as possible agent for cosmeceutical potential.
透明质酸（HA）是皮肤细胞外基质的重要组成部分，其降解会导致皱纹产生。参与透明质酸解聚的透明质酸结合蛋白（HYBID）是真皮中HA降解的主要负责因素。本研究旨在鉴定能够有效抑制HYBID表达并保护HA不被降解的天然植物材料。对各种植物提取物进行筛选，以检测其对正常人皮肤成纤维细胞（NHDF）中组胺诱导的HYBID mRNA表达的抑制作用。通过在NHDF中孵育异硫氰酸荧光素（FITC）标记的大分子HA（1200 - 1600 kDa）一定时间，然后用高效液相色谱法测量培养基中不同大小的FITC标记的HA，来评估HA的分子大小分布。在380种植物提取物中，我们发现茵陈花提取物（ACFE）是抑制HYBID表达以及保护大分子HA不被降解方面最有效的试剂。后续的机制阐释研究表明，ACFE通过调节特定miRNA miR - 486 - 5p的表达，对HYBID的表达进行表观遗传调控，已知该miRNA可直接靶向并抑制HYBID的表达。我们的活性化合物搜索在ACFE中鉴定出1 - 咖啡酰 - 3 - 羟基丁烷和3 - 咖啡酰 - 1 - 羟基丁烷这两种新化合物，我们分别将其命名为川七香薷素I和川七香薷素II。这是首次有报告表明含有两种新型活性化合物的茵陈可抑制HYBID表达以及透明质酸降解，因此，可作为具有潜在药妆用途的可能试剂。
