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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Elsevier
2025-02-01
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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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