Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle

Mira Choi,Sunhyae Jang,Ohsang Kwon,Soon-Jin Choi,Hye-In Choi,Sungjoo Tommy Hwang,Bo-Mi Kang

doi:10.1038/s41598-019-53612-5

Mira Choi, Sunhyae Jang + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-53612-5

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Abstract

Shikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.

Highlights

Shikimic acid (SA) has recently been found to be a major component of plant stem cells
In this study, we investigated the effect of SA on hair growth in vivo, confirmed using the anagen induction assay in C57BL/6 mice as well as in cultured human dermal papilla cells, outer root sheath cells, and ex vivo human hair follicles (HFs) organ culture
Our study demonstrated that SA treatment for human dermal papilla cells (hDPCs) significantly increased mRNA expression of c-myc, HGF, keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), which are known to stimulate hair growth[28,29,30]

Summary

Introduction

Shikimic acid (SA) has recently been found to be a major component of plant stem cells. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. Stem cells have the ability to differentiate into various cells with specific functions depending on the environment; they have the ability to repeatedly divide and renew[1] Because of these characteristics, active research is underway on the use of stem cells to restore function to organs and tissues in various diseases; some clinical application has been achieved[2]. Stem cell treatment has been extensively studied and proved effective in various hair loss diseases[3,4]. It has been reported that SA is a major component of plant stem cells or callus that induces tissue regeneration when a plant is injured[9]. It was seen that SA induced mRNA expression of insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and vascular endothelial growth factor (VEGF) in the mouse hair follicle[12]

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