Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice

Background Vitiligo is a depigmentation disorder with an undefined specific pathogenesis, with the autoimmune theory being a prominent etiology. Mycophenolate mofetil (MMF), a novel immunosuppressant, selectively inhibits inosine 5-monophosphate dehydrogenase (IMPDH), crucial for lymphocyte DNA synt...

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Main Authors: Yuan Guo, Yi-fei Yang, Yanhua-Li, Yun Zhang, Haixia-Shi
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2544880
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author Yuan Guo
Yi-fei Yang
Yanhua-Li
Yun Zhang
Haixia-Shi
author_facet Yuan Guo
Yi-fei Yang
Yanhua-Li
Yun Zhang
Haixia-Shi
author_sort Yuan Guo
collection DOAJ
description Background Vitiligo is a depigmentation disorder with an undefined specific pathogenesis, with the autoimmune theory being a prominent etiology. Mycophenolate mofetil (MMF), a novel immunosuppressant, selectively inhibits inosine 5-monophosphate dehydrogenase (IMPDH), crucial for lymphocyte DNA synthesis. Recent research has highlighted MMF’s efficacy in vitiligo treatment; however, the precise mechanism remains unclear. This study aimed to explore the therapeutic impact and mechanism of vitiligo.Methods We enrolled guinea pigs and C57/BL6 mice which were randomly divided into the hydroquinone group, the MMF & hydroquinone group, and the control group. Skin biopsy specimens were collected from designated areas which were stained using hematoxylin and eosin (H&E), Masson-Fontana (M-F), and immunofluorescence techniques. To elucidate the pharmacological mechanisms underlying the effects of MMF, real-time polymerase chain reaction (PCR) and western blotting analyses were performed.Results A comparative analysis revealed a notable enhanced pigmentation in the MMF-conjunction group. Subsequent to MMF application, there was a significant augmentation in both the number of melanocytes within the basal layer and melanin-containing hair follicles. MMF activated tyrosinase (TYR), which had been suppressed by hydroquinone, and led to an upregulation of melanin-associated genes such as TYR, TYRP-1, MITF, and SILV. Additionally, there was an increase in WNT pathway-related proteins, including β-catenin, GSK3β, Axin2, Dkk, and Dact2. MMF effectively mitigated the vitiligo-like increase in IFN-γ induced by hydroquinone safely.Conclusion MMF exhibits a notable capacity to ameliorate the pigment-loss effect associated with hydroquinone through the activation of the WNT signaling pathway. Consequently, MMF emerges as a promising therapeutic agent for mitigating skin pigmentation.
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spelling doaj-art-fe75f7b01eeb44a68fca8444340ec1412025-08-20T03:41:50ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2544880Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and miceYuan Guo0Yi-fei Yang1Yanhua-Li2Yun Zhang3Haixia-Shi4Department of Dermatology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Dermatology, The Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Dermatology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Dermatology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Dermatology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaBackground Vitiligo is a depigmentation disorder with an undefined specific pathogenesis, with the autoimmune theory being a prominent etiology. Mycophenolate mofetil (MMF), a novel immunosuppressant, selectively inhibits inosine 5-monophosphate dehydrogenase (IMPDH), crucial for lymphocyte DNA synthesis. Recent research has highlighted MMF’s efficacy in vitiligo treatment; however, the precise mechanism remains unclear. This study aimed to explore the therapeutic impact and mechanism of vitiligo.Methods We enrolled guinea pigs and C57/BL6 mice which were randomly divided into the hydroquinone group, the MMF & hydroquinone group, and the control group. Skin biopsy specimens were collected from designated areas which were stained using hematoxylin and eosin (H&E), Masson-Fontana (M-F), and immunofluorescence techniques. To elucidate the pharmacological mechanisms underlying the effects of MMF, real-time polymerase chain reaction (PCR) and western blotting analyses were performed.Results A comparative analysis revealed a notable enhanced pigmentation in the MMF-conjunction group. Subsequent to MMF application, there was a significant augmentation in both the number of melanocytes within the basal layer and melanin-containing hair follicles. MMF activated tyrosinase (TYR), which had been suppressed by hydroquinone, and led to an upregulation of melanin-associated genes such as TYR, TYRP-1, MITF, and SILV. Additionally, there was an increase in WNT pathway-related proteins, including β-catenin, GSK3β, Axin2, Dkk, and Dact2. MMF effectively mitigated the vitiligo-like increase in IFN-γ induced by hydroquinone safely.Conclusion MMF exhibits a notable capacity to ameliorate the pigment-loss effect associated with hydroquinone through the activation of the WNT signaling pathway. Consequently, MMF emerges as a promising therapeutic agent for mitigating skin pigmentation.https://www.tandfonline.com/doi/10.1080/07853890.2025.2544880Melanogenesismycophenolate mofetilWNT
spellingShingle Yuan Guo
Yi-fei Yang
Yanhua-Li
Yun Zhang
Haixia-Shi
Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
Annals of Medicine
Melanogenesis
mycophenolate mofetil
WNT
title Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
title_full Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
title_fullStr Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
title_full_unstemmed Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
title_short Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice
title_sort therapeutic effects of topical mycophenolate mofetil on hydroquinone induced depigmentation in guinea pigs and mice
topic Melanogenesis
mycophenolate mofetil
WNT
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2544880
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