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

IF 4.3 3区医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2024-09-23 DOI:10.3390/ph17091252

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

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Abstract

Background: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves β-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. Ferula 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 Ferula samarcandica. Feshurin was shown to induce GSK-3β phosphorylation, resulting in the translocation of β-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.

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阿魏中提取的Feshurin的体外抗白癜风作用及其作用机制

背景白癜风是一种以皮肤脱色为特征的复杂疾病；涉及β-catenin的典型Wnt信号通路在促进黑色素细胞产生黑色素方面起着至关重要的作用。靶向抑制 Janus 激酶 JAK-STAT 通路可有效减少趋化因子 C-X-C motif 配体 CXCL10 的分泌，从而保护黑色素细胞。阿魏作为一种治疗方案已经应用了很长时间，但用于治疗白癜风的方法还未见记载：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、Western 印迹法、qRT-PCR 法和 ELISA 法。通过分子对接验证了飞鹤灵对 JAK1 的抑制作用：结果：从阿魏中分离出倍半萜香豆素 feshurin。结果表明，Feshurin 能诱导 GSK-3β 磷酸化，导致 β-catenin 转位至细胞核。这种转位随后会上调小眼症相关转录因子（MITF）的转录，导致酪氨酸酶活性和黑色素生成增加。此外，费舒林还能通过 JAK-STAT 信号通路抑制趋化因子 CXCL10 的产生，这一点已通过分子对接得到验证：根据这些研究结果，可以得出结论：飞鹤素在开发新型抗白癜风疗法方面具有巨大潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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