Costunolide promotes the proliferation of human hair follicle dermal papilla cells and induces hair growth in C57BL/6 mice

J Cosmet Dermatol. 2019 Feb;18(1):414-421. doi: 10.1111/jocd.12674. Epub 2018 May 28.

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.

Keywords: TGF; BMP/Smad; Shh/Gli; WNT/ β-catenin; costunolide; human hair follicle dermal papilla cells; mouse hair growth.

MeSH terms

  • 5-alpha Reductase Inhibitors / administration & dosage
  • 5-alpha Reductase Inhibitors / pharmacology*
  • Administration, Cutaneous
  • Animals
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Cholestenone 5 alpha-Reductase / metabolism
  • Female
  • Gene Expression / drug effects
  • Hair / growth & development*
  • Hair Follicle / cytology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Random Allocation
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / pharmacology*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Wnt Signaling Pathway / drug effects
  • Zinc Finger Protein GLI1 / genetics
  • Zinc Finger Protein GLI1 / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • 5-alpha Reductase Inhibitors
  • GLI1 protein, human
  • Sesquiterpenes
  • Smad Proteins
  • Transforming Growth Factor beta1
  • Zinc Finger Protein GLI1
  • beta Catenin
  • costunolide
  • Cholestenone 5 alpha-Reductase