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

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.

We aimed to evaluate the therapeutic efficacy of CCL against vitiligo, elucidate its underlying pharmacological mechanisms, and identify its potential active monomer.

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.

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.

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.