Carum carvi L. alleviates skin depigmentation by suppressing STAT1-mediated inflammatory responses

IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL
Journal of ethnopharmacology Pub Date : 2027-02-10 Epub Date: 2026-10-20 DOI:10.1016/j.jep.2026.122555
Wancheng Sun, Wenjing Wei, Dengqiu Xu, Abudureyimu Alimujiang, Hongzhi Wang, Jingcheng Zhao, Xuehua Yan, Zhijian Li, Fan Zhou
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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.
Carum carvi .通过抑制stat1介导的炎症反应来减轻皮肤色素沉着。
民族药理学相关性:白癜风是一种以CD8+ T细胞介导的黑素细胞破坏为特征的获得性脱色疾病。虽然JAK抑制剂表现出疗效,但其临床应用受到不良反应、高成本和儿科禁忌症的限制。Carum carvi L. (CCL)是维吾尔和藏医学中备受推崇的药用植物,常被用于治疗难治性皮肤病,特别是白癜风。研究目的:我们旨在评估CCL对白癜风的治疗效果,阐明其潜在的药理机制,并确定其潜在的活性单体。方法和材料:采用单苯诱导的白癜风小鼠模型,评估口服CCL后的宏观、组织学和分子恢复情况。为了阐明其药理机制和鉴定关键生物活性成分,我们整合了RNA-seq、UPLC-Orbitrap-MS/MS化学分析、网络药理学、血清成分筛选和分子对接。鉴定的候选单体随后通过B16F10细胞测定和小鼠体内模型进行验证。结果:在体内,CCL和Rob均恢复了色素沉着,恢复了黑色素沉积和功能性滤泡黑色素细胞。体外和体内实验证实Rob抑制STAT1的激活并减弱下游CXCL9/10趋化因子级联。这种靶向调节减少了局部炎症,其特征是巨噬细胞浸润减少,表型向促修复(CD206+)巨噬细胞转移,并限制了CD8+ T细胞的募集。结论:CCL及其活性单体Rob可有效减轻免疫介导的黑素细胞破坏并促进色素沉着。Rob通过抑制stat1 -巨噬细胞- cd8 + T细胞炎症轴驱动靶向治疗干预。这些发现表明,CCL是一种有希望的、多靶点的白癜风自然疗法。
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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
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.
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