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  2. The critical role of glutathione redox homeostasis towards oxidation in ermanin-induced melanogenesis

The critical role of glutathione redox homeostasis towards oxidation in ermanin-induced melanogenesis

  • Free Radic Biol Med. 2021 Nov 20;176:392-405. doi: 10.1016/j.freeradbiomed.2021.09.017.
Qiong Ding 1 Lin Luo 2 Lan Yu 2 Si-Lu Huang 2 Xiao-Qin Wang 1 Bo Zhang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, PR China.
  • 2 Pharmacology Department, School of Pharmacy, Shihezi University, Shihezi, 832002, PR China.
  • 3 Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, PR China; Pharmacology Department, School of Pharmacy, Shihezi University, Shihezi, 832002, PR China. Electronic address: bozhang_lzu@126.com.
Abstract

Vitiligo is a depigmented disease featured as diagnosis simplicity and cure difficulty. Its occurrence and development are associated with a variety of factors, including oxidative stress, heredity and immunity, etc. Existing drugs for the treatment of vitiligo are to reduce the death of melanocytes and induce pigment accumulation as the main treatment strategy. Ermanin, a member of the Flavonoids, is extracted from bee glue which is wildly used to treat vitiligo in traditional Chinese medicine. Therefore, this article discusses the relationship between melanogenesis and glutathione redox homeostasis by ermanin via biochemical and free radical approaches in vivo and in vitro. In this study, we found that ermanin effectively increased the melanin content at the in vivo model (zebrafish). Moreover, the melanin levels at the in vitro models (B16F10 cells and primary melanocytes) were also increased significantly accompanied with a shift of glutathione redox homeostasis towards oxidation. Ermanin also significantly enhanced the activity of Tyrosinase. Meanwhile, ermanin increased the expression levels of TYR, TRP-1, and DCT genes, while ROS accumulation and glutathione depletion mediated the accumulation of Pigments caused by ermanin, which increased the production of Pigments and regulated the expression mRNA levels of TYR and DCT genes. From the perspective of pigment production regulation pathways, western blot showed that the pigment accumulation caused by ermanin was closely related to the CREB-MITF pathways, it activated CREB, TYR, TRP-1, and DCT proteins. The use of CREB specific inhibitor 666-15 and MITF inhibitor ML329 confirmed that the pigment accumulation caused by ermanin was positively correlated with CREB and MITF proteins. Our findings revealed the potential mechanisms by which ermanin promoted the production of melanin through activated CREB-MITF signaling pathway and glutathione redox homeostasis towards oxidation function as a signal are beneficial to melanin production and will help develop novel therapeutic approaches for vitiligo.

Keywords

CREB-MITF pathway; Ermanin; Melanogenesis; ROS; Redox homeostasis.

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