费舒林体外抗白癜风作用及其作用机制

The Anti-Vitiligo Effects of Feshurin In Vitro from and the Mechanism of Action.

作者信息

Nueraihemaiti Mayire, Deng Zang, Kamoldinov Khamidulla, Chao Niu, Habasi Maidina, Aisa Haji Akber

机构信息

State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.

University of Chinese Academy of Sciences, Beijing 100039, China.

出版信息

Pharmaceuticals (Basel). 2024 Sep 23;17(9):1252. doi: 10.3390/ph17091252.

DOI:10.3390/ph17091252

PMID:39338414

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11434855/

Abstract

BACKGROUND

Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves -catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented.

METHODS

CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1.

RESULTS

The sesquiterpene coumarin feshurin was separated from . Feshurin was shown to induce GSK-3 phosphorylation, resulting in the translocation of -catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking.

CONCLUSIONS

Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics.

摘要

背景

白癜风是一种以皮肤色素脱失为特征的复杂疾病；涉及β-连环蛋白的经典Wnt信号通路在促进黑素细胞产生黑色素方面起着关键作用。靶向抑制Janus激酶JAK-STAT通路可有效减少趋化因子C-X-C基序配体CXCL10的分泌，从而保护黑素细胞。[某种物质]长期以来一直被用作一种治疗方案；然而，其用于治疗白癜风此前尚无文献记载。

方法

采用CCK-8检测法、细胞内黑色素含量检测法、酪氨酸酶活性检测法、蛋白质免疫印迹法、实时荧光定量聚合酶链反应法和酶联免疫吸附测定法。使用分子对接验证了呋甾醇对JAK1的抑制作用。

结果

从[某种物质]中分离出倍半萜香豆素呋甾醇。呋甾醇被证明可诱导糖原合酶激酶-3磷酸化，导致β-连环蛋白易位至细胞核。这种易位随后上调了小眼相关转录因子（MITF）的转录，导致酪氨酸酶活性和黑色素生成增加。此外，呋甾醇通过JAK-STAT信号通路抑制趋化因子CXCL10的产生，这一点通过分子对接得到了验证。