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The Anti-Vitiligo Effects of Feshurin In Vitro from Ferula samarcandica and the Mechanism of Action
Mayire Nueraihemaiti1,2, Zang Deng1, Khamidulla Kamoldinov3
1State 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.
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.
Insights
Feshurin, derived from Ferula samarcandica, promotes melanin production by activating the Wnt/β-catenin pathway and inhibits inflammation via the JAK-STAT pathway, showing potential as a novel vitiligo therapeutic.
Area of Science:
- Pharmacology
- Dermatology
- Natural Products Chemistry
Background:
- Vitiligo is a depigmentation disorder where Wnt/β-catenin signaling promotes melanogenesis.
- The Janus kinase (JAK)-STAT pathway regulates inflammation by controlling chemokine (C-X-C motif) ligand 10 (CXCL10) secretion.
- Ferula species have traditional uses, but their application in vitiligo is undocumented.
Purpose of the Study:
- To investigate the potential of feshurin, a compound from Ferula samarcandica, as a therapeutic agent for vitiligo.
Main Methods:
- Feshurin was isolated and its effects were analyzed using CCK-8, melanin content, tyrosinase activity, Western blotting, qRT-PCR, and ELISA.
- Molecular docking was employed to verify the inhibitory effects of feshurin on JAK1.
Main Results:
- Feshurin induced GSK-3β phosphorylation, leading to β-catenin nuclear translocation, MITF upregulation, and increased melanin production.
- Feshurin inhibited CXCL10 production through the JAK-STAT pathway, confirmed by molecular docking.
Conclusions:
- Feshurin demonstrates significant potential for developing novel therapeutics against vitiligo.
