{"title":"Carum carvi L. alleviates skin depigmentation by suppressing STAT1-mediated inflammatory responses","authors":"Wancheng Sun, Wenjing Wei, Dengqiu Xu, Abudureyimu Alimujiang, Hongzhi Wang, Jingcheng Zhao, Xuehua Yan, Zhijian Li, Fan Zhou","doi":"10.1016/j.jep.2026.122555","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vitiligo is an acquired depigmenting disorder characterized by CD8<sup>+</sup> T cell-mediated melanocyte destruction. While JAK inhibitors exhibit efficacy, their clinical application is limited by adverse effects, high costs, and pediatric contraindications. <em>Carum carvi</em> L<em>.</em> (CCL), an esteemed medicinal plant in traditional Uyghur and Tibetan medicine, is frequently prescribed to treat refractory skin diseases, notably vitiligo.</div></div><div><h3>Aim of the study</h3><div>We aimed to evaluate the therapeutic efficacy of CCL against vitiligo, elucidate its underlying pharmacological mechanisms, and identify its potential active monomer.</div></div><div><h3>Methods and materials</h3><div>A monobenzone-induced vitiligo mouse model was utilized to assess macroscopic, histological, and molecular recovery following oral administration of the CCL. To elucidate the pharmacological mechanisms and identify key bioactive constituents, we integrated RNA-seq, UPLC-Orbitrap-MS/MS chemical profiling, network pharmacology, serum constituent screening, and molecular docking. The identified candidate monomer was subsequently validated through B16F10 cell assays, and an in vivo murine model.</div></div><div><h3>Results</h3><div>In vivo, both the CCL and Rob restored repigmentation, restoring melanin deposition and functional follicular melanocytes. In vitro and in vivo experiments confirmed that Rob inhibited STAT1 activation and attenuated the downstream CXCL9/10 chemokine cascade. This targeted modulation reduced localized inflammation, characterized by decreased macrophage infiltration and a phenotypic shift toward pro-repair (CD206<sup>+</sup>) macrophages, and restricted CD8<sup>+</sup> T cell recruitment.</div></div><div><h3>Conclusions</h3><div>CCL and its active monomer Rob effectively mitigates immune-mediated melanocyte destruction and promotes repigmentation. Rob drives targeted therapeutic intervention by suppressing the STAT1-macrophage-CD8<sup>+</sup> T cell inflammatory axis. These findings suggest CCL as a promising, multi-targeted natural therapy for vitiligo.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"374 ","pages":"Article 122555"},"PeriodicalIF":6.8000,"publicationDate":"2027-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874126014108","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/10/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance
Vitiligo is an acquired depigmenting disorder characterized by CD8+ T cell-mediated melanocyte destruction. While JAK inhibitors exhibit efficacy, their clinical application is limited by adverse effects, high costs, and pediatric contraindications. Carum carvi L. (CCL), an esteemed medicinal plant in traditional Uyghur and Tibetan medicine, is frequently prescribed to treat refractory skin diseases, notably vitiligo.
Aim of the study
We aimed to evaluate the therapeutic efficacy of CCL against vitiligo, elucidate its underlying pharmacological mechanisms, and identify its potential active monomer.
Methods and materials
A monobenzone-induced vitiligo mouse model was utilized to assess macroscopic, histological, and molecular recovery following oral administration of the CCL. To elucidate the pharmacological mechanisms and identify key bioactive constituents, we integrated RNA-seq, UPLC-Orbitrap-MS/MS chemical profiling, network pharmacology, serum constituent screening, and molecular docking. The identified candidate monomer was subsequently validated through B16F10 cell assays, and an in vivo murine model.
Results
In vivo, both the CCL and Rob restored repigmentation, restoring melanin deposition and functional follicular melanocytes. In vitro and in vivo experiments confirmed that Rob inhibited STAT1 activation and attenuated the downstream CXCL9/10 chemokine cascade. This targeted modulation reduced localized inflammation, characterized by decreased macrophage infiltration and a phenotypic shift toward pro-repair (CD206+) macrophages, and restricted CD8+ T cell recruitment.
Conclusions
CCL and its active monomer Rob effectively mitigates immune-mediated melanocyte destruction and promotes repigmentation. Rob drives targeted therapeutic intervention by suppressing the STAT1-macrophage-CD8+ T cell inflammatory axis. These findings suggest CCL as a promising, multi-targeted natural therapy for vitiligo.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.