Bacillus/Trapa japonica Fruit Extract Ferment Filtrate enhances human hair follicle dermal papilla cell proliferation via the Akt/ERK/GSK-3\u03b2 signaling pathway

Gun-He Nam,Je-Geun Yoo,Ye-Seul Park,Kyung-Jo Jo,Jin Dong Jang,Sang-Yong Kim,Hye Won Kawk,Sang Moon Kang,Young-Min Kim

doi:10.1186/s12906-019-2514-8

Abstract

BackgroundDespite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, creating a need for new treatments to control hair loss and prevent balding. Treatments based on plant-derived compounds could potentially prevent hair loss. Human hair follicle dermal papilla (HDP) cells, a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions such as androgenic alopecia. We examined the effect of Bacillus/Trapa japonica fruit ferment filtrate extracts (TJFs) on HDP cells to determine whether activation of the Akt/ERK/GSK-3β signaling pathway improved HDP cell proliferation.MethodsWe prepared TJFs using various methods. The extract properties were analyzed using WST-1, Lowry, and cell migration assays as well as immunofluorescence staining. We also determined the cell cycle stage and performed western blotting and an in ovo chick chorioallantoic membrane assay. Last, we constructed an organotypic three-dimensional cell culture model for immunohistochemical use.ResultsOur study confirmed that the TJFs contained numerous peptides and five unknown fractions. The TJFs stimulated HDP cell proliferation and migration via the Akt/ERK/GSK-3β signaling pathway. To verify that the Akt/ERK/GSK-3β pathway affected HDP cell proliferation, we treated HDP cells with LY294002 (an Akt inhibitor), BIO (a GSK-3β inhibitor), and PD98059 (an ERK inhibitor). The TJFs also induced cell cycle progression, inhibited type І 5α-reductase, decreased apoptosis, and enhanced angiogenesis (vascular expansion). In addition to these signaling pathways, proteins including insulin-like growth factor-1 and keratinocyte growth factor, stimulating hair growth, were detected in the three-dimensional cell culture model.ConclusionsOur results confirmed that TJFs enhance HDP cell proliferation via the Akt/ERK/GSK-3β signaling pathway, suggesting a potential treatment for alopecia.

Highlights

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, creating a need for new treatments to control hair loss and prevent balding
We investigated the effect of Trapa japonica fruit ferment filtrate extracts (TJFs) on Human hair Follicle dermal papilla cells (HDPs) cells both in vitro and ex vivo to identify and isolate new substances for alopecia treatment
The results from this study have demonstrated that the treatment of HDP cells with TJFs promoted hair growth activity, cell cycle progression, and vascular expansion

Summary

Introduction

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, creating a need for new treatments to control hair loss and prevent balding. Reducing HDP apoptosis and inhibiting the production of type I 5α-reductase is effective in preventing alopecia, and inducing HDP growth is critical for its treatment. The Akt/ ERK/GSK-3β pathway in HDP cells promotes hair growth [13,14,15,16]. A serine/threonine kinase, is a critical protein that acts downstream of the P13K pathway to modulate the response of cells to external stimuli and regulate cell proliferation and survival by controlling various internal signals [17]. The ERK signaling pathway controls the cell cycle of proliferation, differentiation, and apoptosis [20]. The growth of HDP cells via vascular expansion and hair via potassium channels is promoted through the Akt/ ERK/GSK-3β signaling pathway [21]

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Discussion

Conclusion