Abstract
BACKGROUND: Costunolide (COS), a naturally occurring sesquiterpene lactone, is known to exert anti-inflammatory, antioxidant, and anticancer effects. This study was undertaken to investigate the effects of costunolide on the promotion of hair growth. METHODS: Real-time cell analyzer (RTCA), measurement of 5α-reductase activity, mRNA expression, and Western blotting were adopted to address whether COS can stimulate the proliferation of human hair follicle dermal papilla cells (hHFDPCs). The effect of COS on in vivo hair growth was examined by reconstitution assay and shaven dorsal skin in C57BL/6 mice. RESULTS: Costunolide significantly promoted the proliferation of hHFDPCs, which is comparable to that of tofacitinib. COS also inhibited the 5α-reductase activity in hHFDPCs. While COS increased the level of β-catenin and Gli1 mRNA and proteins, it suppressed transforming growth factor (TGF)-β1-induced phosphorylation of Smad-1/5 in hHFDPCs. COS increased the number of cultured hHFDPCs to induce hair follicles from mouse epidermal cells in Spheres formation of reconstitution assay. Topical application of COS on the shaven back of C57BL/6 mice significantly improved the hair growth. CONCLUSIONS: Our results illustrate that COS promotes hair growth in vitro and in vivo by regulating the amount of growth factors and/or the activity of cellular responses through coordination of the WNT-β-catenin, hedgehog-Gli, and TGF-β1-Smad pathways.