Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation

Abstract 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 natu...

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Main Authors: Kazal Boron Biswas, Yuka Kawai, Satoshi Nakagawa, Kyoko Kanai, Hiroyuki Kojima, Teruaki Masutani, Masayoshi Oyama, Arunasiri Iddamalgoda, Kotaro Sakamoto
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86320-4
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author Kazal Boron Biswas
Yuka Kawai
Satoshi Nakagawa
Kyoko Kanai
Hiroyuki Kojima
Teruaki Masutani
Masayoshi Oyama
Arunasiri Iddamalgoda
Kotaro Sakamoto
author_facet Kazal Boron Biswas
Yuka Kawai
Satoshi Nakagawa
Kyoko Kanai
Hiroyuki Kojima
Teruaki Masutani
Masayoshi Oyama
Arunasiri Iddamalgoda
Kotaro Sakamoto
author_sort Kazal Boron Biswas
collection DOAJ
description Abstract 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.
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spelling doaj-art-28a3674eadd74fbb971224b9913931ff2025-01-19T12:19:54ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-86320-4Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradationKazal Boron Biswas0Yuka Kawai1Satoshi Nakagawa2Kyoko Kanai3Hiroyuki Kojima4Teruaki Masutani5Masayoshi Oyama6Arunasiri Iddamalgoda7Kotaro Sakamoto8Department of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Laboratory of Pharmacognosy, Gifu Pharmaceutical UniversityDepartment of Research and Development, Ichimaru Pharcos Co. Ltd.Department of Research and Development, Ichimaru Pharcos Co. Ltd.Abstract 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.https://doi.org/10.1038/s41598-025-86320-4Artemisia capillaris flower extractHYBIDHyaluronic acidKawarayomoginmiR-486-5p
spellingShingle Kazal Boron Biswas
Yuka Kawai
Satoshi Nakagawa
Kyoko Kanai
Hiroyuki Kojima
Teruaki Masutani
Masayoshi Oyama
Arunasiri Iddamalgoda
Kotaro Sakamoto
Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
Scientific Reports
Artemisia capillaris flower extract
HYBID
Hyaluronic acid
Kawarayomogin
miR-486-5p
title Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
title_full Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
title_fullStr Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
title_full_unstemmed Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
title_short Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
title_sort artemisia capillaris with two novel active compounds kawarayomogin i and ii inhibits hybid kiaa1199 expression as well as hyaluronic acid degradation
topic Artemisia capillaris flower extract
HYBID
Hyaluronic acid
Kawarayomogin
miR-486-5p
url https://doi.org/10.1038/s41598-025-86320-4
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