Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways

Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At conce...

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Main Authors: Saki Okamoto, Saya Kakimaru, Mayuko Koreishi, Mika Sakamoto, Yoshimasa Nakamura, Hideya Ando, Yoshio Tsujino, Ayano Satoh
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Functional Foods
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Online Access:http://www.sciencedirect.com/science/article/pii/S1756464625000143
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author Saki Okamoto
Saya Kakimaru
Mayuko Koreishi
Mika Sakamoto
Yoshimasa Nakamura
Hideya Ando
Yoshio Tsujino
Ayano Satoh
author_facet Saki Okamoto
Saya Kakimaru
Mayuko Koreishi
Mika Sakamoto
Yoshimasa Nakamura
Hideya Ando
Yoshio Tsujino
Ayano Satoh
author_sort Saki Okamoto
collection DOAJ
description Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25–50 μM, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)-mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.
format Article
id doaj-art-b1191667c09c4b0aa75112adb5f16d17
institution Kabale University
issn 1756-4646
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series Journal of Functional Foods
spelling doaj-art-b1191667c09c4b0aa75112adb5f16d172025-02-09T04:59:55ZengElsevierJournal of Functional Foods1756-46462025-02-01125106672Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathwaysSaki Okamoto0Saya Kakimaru1Mayuko Koreishi2Mika Sakamoto3Yoshimasa Nakamura4Hideya Ando5Yoshio Tsujino6Ayano Satoh7Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-0082, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-0082, JapanGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-0082, JapanNational Institute of Genetics, ROIS, Yata 1111, Mishima, Shizuoka 411-8540, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanDepartment of Applied Chemistry and Biotechnology, Okayama University of Science, Okayama 700-0005, JapanGraduate School of Science, Technology, and Innovation, Kobe University, Rokkodai, Nada, Kobe 657-8501, Hyogo, Japan; Corresponding authors.Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-0082, Japan; Corresponding authors.Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25–50 μM, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)-mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.http://www.sciencedirect.com/science/article/pii/S1756464625000143AntioxidantLysosomesAutophagyResveratrolSkin fibroblastsBioactive compounds
spellingShingle Saki Okamoto
Saya Kakimaru
Mayuko Koreishi
Mika Sakamoto
Yoshimasa Nakamura
Hideya Ando
Yoshio Tsujino
Ayano Satoh
Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
Journal of Functional Foods
Antioxidant
Lysosomes
Autophagy
Resveratrol
Skin fibroblasts
Bioactive compounds
title Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
title_full Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
title_fullStr Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
title_full_unstemmed Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
title_short Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways
title_sort resveratrol a food derived polyphenol promotes melanosomal degradation in skin fibroblasts through coordinated activation of autophagy lysosomal and antioxidant pathways
topic Antioxidant
Lysosomes
Autophagy
Resveratrol
Skin fibroblasts
Bioactive compounds
url http://www.sciencedirect.com/science/article/pii/S1756464625000143
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