Background 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. 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. Methods We 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. Results Our 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. Conclusions Our results confirmed that TJFs enhance HDP cell proliferation via the Akt/ERK/GSK-3β signaling pathway, suggesting a potential treatment for alopecia.

We have previously shown that Trapa japonica fruit extract (TJE) as well as its fermented extract (FTJ) can be potentially used to treat alopecia. In the current study, a newly synthesized peptide (PEP) was detected in an active compound isolated from FTJ. Several biological assays were conducted to verify the antiaging effects of TJE, FTJ, and PEP on the skin. We examined the effects of TJE, FTJ, and PEP on cell viability, collagen synthesis, and inhibition of mRNA expression of matrix metalloproteinases (MMPs), induced by tumor necrosis factor alpha (TNF-α), in human dermal fibroblasts (HDFs). In addition, a wound-healing assay of the human keratinocyte cell line (HaCaT) and a clinical study of antiaging activity were conducted. The findings confirmed that PEP exerted an effect on cell proliferation in a dose-dependent manner. Treatment with TJE, FTJ, and PEP increased collagen synthesis but inhibited TNF-α-induced mRNA expression of MMPs. Compared with TJE and FTJ, PEP promoted a significant level of wound recovery in HaCaT cells and also exhibited antiaging effect, as demonstrated by a clinical study. These results suggest that PEP shows potential as a skin antiaging cosmetic product.

The Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).

In this study, Eucommia ulmoides Oliver extracts was studied in order to see any effects on the β-hexosaminidase release suppression of RBL-2H3 cells and on the expression of filaggrin, transglutaminase-1 (TGase-1) and cornified cell envelope (CE) related to the recovery of HaCaT keratinocyte skin barrier. Results showed that Eucommia ulmoides Oliver extracts reduced β-hexosaminidase release in RBL-2H3 cells and increased the effects of Eucommia ulmoides Oliver extract on the expression of filaggrin, transglutaminase-1 (TGase-1) and cornified cell envelope (CE) in HaCaT keratinocytes. Taken together, these results suggested that Eucommia ulmoides Oliver extract may be applicable for keratinocyte differentiation.

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