Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.

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 unde...

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Main Authors: Hirokazu Kubo, Mariko Moriyama, Saya Goto, Yuko Miyake, Maki Nakamura, Yuki Ozeki, Yukio Nakamura, Hiroyuki Moriyama
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0325242
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author Hirokazu Kubo
Mariko Moriyama
Saya Goto
Yuko Miyake
Maki Nakamura
Yuki Ozeki
Yukio Nakamura
Hiroyuki Moriyama
author_facet Hirokazu Kubo
Mariko Moriyama
Saya Goto
Yuko Miyake
Maki Nakamura
Yuki Ozeki
Yukio Nakamura
Hiroyuki Moriyama
author_sort Hirokazu Kubo
collection DOAJ
description 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.
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spelling doaj-art-94aeb4c1cbde4c8ba8c24d2e436dce232025-08-20T03:20:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032524210.1371/journal.pone.0325242Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.Hirokazu KuboMariko MoriyamaSaya GotoYuko MiyakeMaki NakamuraYuki OzekiYukio NakamuraHiroyuki MoriyamaSalvia 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.https://doi.org/10.1371/journal.pone.0325242
spellingShingle Hirokazu Kubo
Mariko Moriyama
Saya Goto
Yuko Miyake
Maki Nakamura
Yuki Ozeki
Yukio Nakamura
Hiroyuki Moriyama
Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
PLoS ONE
title Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
title_full Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
title_fullStr Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
title_full_unstemmed Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
title_short Sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte-derived GM-CSF.
title_sort sage extract and ascorbic acid derivative inhibit melanogenesis via downregulating keratinocyte derived gm csf
url https://doi.org/10.1371/journal.pone.0325242
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