The extract of Cyperus rotundus L. rhizome promotes hair growth and modulates hair cycle in vivo and in vitro.

Hair loss, a multifactorial disorder characterized by follicular miniaturization and excessive shedding, significantly impacts psychological well-being and quality of life. Cyperus rotundus L. rhizome, a traditional Chinese medicine, has been used for various ailments; however, its efficacy in hair loss remains unexamined. This study is the first to evaluate the hair growth-promoting effects of ethanol extract from C. rotundus L. rhizomes (CR) on mouse primary dermal papilla cells (MDPCs) and human immortalized hair DPCs (IHHDPCs) using CCK-8, scratch assay, RT-qPCR, and Western blot (WB). CR treatment enhanced Wnt/β-Catenin signaling by upregulating Wnt10b, increasing β-Catenin levels and nuclear translocation, while downregulating TGF-β1, BMP4, and DKK1 in MDPCs. These molecular events promoted cell proliferation and increased secretion of growth factors, including IGF-1, KGF, and VEGF, thereby stimulating hair growth and prolonging the anagen phase, and was validated in an ex-vivo hair follicle (HF) organ model. Chromatographic analysis identified the petroleum ether fraction (CRP), rich in sesquiterpenes, as the main bioactive component. Both CR and CRP enhanced IHHDPC proliferation, migration, and growth factor expression via the Wnt/β-Catenin pathway, with CRP demonstrating superior activity. Additionally, they stimulated HF cycling, increased follicular density, and upregulated Ki67 and β-Catenin expression in the dorsal skin of C57BL/6 mice. These findings suggest that CR and CRP promote hair growth and modulate hair cycle via enhanced Wnt/β-Catenin pathway, provide a scientific foundation for the potential clinical application of C. rotundus rhizomes in hair loss treatment and the development of related pharmaceuticals or cosmetics.