• Applied Microscopy
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• v.27 no.3
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• pp.321-332
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• 1997

The dermal papilla is known to playa major role in influencing the form and dynamics of the hair follicle, which probably involves regulatory substances crossing the basal lamina. But little is known about the junctions between the dermal papilla and the surrounding epithelial cells of the hair bulb, or between the connective tissue and the epithelial cells on the outside of the hair follicle. This study was performed to identify the ultrastructural differences between dermoepidermal junction of the skin and connective tissue-epithelial junctions on the outside of the hair follicle and around the dermal papilla of normal anagen hair follicles in the human fetal scalp skin. Electron microscopic findings of dermoepidermal junction in scalp skin showed that basal lamina was very irregular and undulated, and it contained many attachment plaques of hemidesmosomes with sub-basal dense plates, tonofilaments, and anchoring filaments. Also invaginations of plasma membrane of basal keratinocytes were seen. There were clear differences both on the outside of the follicle and around the dermal papilla as compared with similar junction in the skin. In particular, neither hemidesmosomes nor tonofilaments, as seen in dermoepidermal junction, were observed in the dermal papilla. Also attachment plaque, sub-basal dense plate and anchoring filaments were not observed at the junction on the outside of the follicle and the dermal papilla. There were some differences between connective tissue-epithelial junctions on the outside of the hair follicle and around the dermal papilla, ie, smoothness of basal lamina and orthogonal arrangement of collagen fibers were seen in the outside of hair follicle, but not in the dermal papilla. These results indicate that the mechanical connection between the hair follicle and the connective tissue component is much weaker than that between the corresponding components in skin, and it reflects the dynamic processes during the anagen phase of the hair follicle compared to the relatively permanent state of the epidermis.

• Journal of Pharmacopuncture
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• v.24 no.2
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• pp.68-75
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• 2021

Objectives: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/β-catenin signaling pathway. We are to investigate β-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. Methods: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by β-catenin expression using RT-PCR and immunostaining experiment. Results: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of β-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that β-catenin expression is a key regulatory function during alopecia progression. Consistently, β-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that β-catenin expression was decreased in RNA level, as well as decreased β-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including β-catenin, but the decreased β-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. Conclusion: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.1-7
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• 2018

Objectives : Puerariae Radix extracts are a rich source of isoflavones that affect the activity of hepatic antioxidant enzymes. However, the effect of these extracts on hair growth in human dermal papilla (DP) cells is unknown. The purpose of this study is to compare the effects between juice and water extracts of Puerariae Radix on the mRNA expression levels of hair growth-related genes in dermal papilla (DP) cells. Methods : The antioxidant activity of juice and water extracts of Puerariae Radix was analyzed using an ABTS assay. The cytotoxicity was analyzed using the MTS assay in DP cells. mRNA expression levels of hair growth-related genes in dermal papilla (DP) cells were analyzed using quantitative RT-PCR analysis. Results : Juice and water extracts of Puerariae Radix showed strong antioxidant activity. The cytotoxicity was confirmed to be higher in the juice extract than the water extract, using the MTS assay on DP cells. The mRNA expression levels of CTNNB1, FGF7, and BMP6 were significantly increased after treatment with water extract, whereas the juice extract did not affect the expression of hair growth-related genes. Conclusions : Our study provides evidence that water extract of Puerariae Radix is effective at inducing hair growth, by promoting the mRNA expression levels of hair growth-related genes. Also in the future, studies should be conducted to investigate the effects of Puerariae radix extracts on the various hair growth mechanisms of dermal papilla cells.

• Korean Journal of Pharmacognosy
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• v.52 no.1
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• pp.34-40
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• 2021

Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

• The Korea Journal of Herbology
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• v.36 no.3
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• pp.39-46
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• 2021

Objectives : Mangifera indica leaves are well known for having a variety of benefits, including anti-inflammatory, anti-tumor, diabetic retinopathy and diabetic vasculosis. However, the effects of Mangifera indica leaves on hair loss inhibition have not been studied. In this study, we investigated to find out the activity of Mangifera indica leaves on hair loss. Methods : 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid(ABTS) analysis was performed to confirm the antioxidant efficacy of the water extract of Mangifera indica leaves (WEML). To examine the effect of WEML on cell viability in dermal papillar (DP) cells, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra Zolium (MTS) analysis was performed. The changes in the mRNA expression level of the hair loss and hair growth-related genes in dermal papilla cells by WEML treatment were confirmed by quantitative RT-PCR. Results : In dermal papilla (DP) cells, ABTS analysis and MTS analysis of WEML showed antioxidant efficacy and low cytotoxicity. As a result of gene expression analysis through Quantitative RT-PCR, no changes in hair growth-related genes BMP6 and CTNNB1 was confirmed. but inhibitory activity of WEML on hair loss-related genes EGR1, SGK, DKK1, SRD5A1 and SRD5A2 was confirmed. Conclusion : We confirmed that WEML has excellent antioxidant efficacy and a inhibitory activity of hair loss-related genes including 5α-reductase genes. These results suggest that Mangifera indica leaves have a potential activity as a hair loss treatment for hair loss and hair growth. Biochemical or molecular biological research on hair loss is needed.

• BMB Reports
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• v.46 no.9
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• pp.460-464
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• 2013

The progression of androgenetic alopecia is closely related to androgen-inducible transforming growth factor (TGF)-${\beta}1$ secretion by hair follicle dermal papilla cells (DPCs) in bald scalp. Physiological levels of androgen exposure were reported to increase reactive oxygen species (ROS) generation. In this study, rat vibrissae dermal papilla cells (DP-6) transfected with androgen receptor showed increased ROS production following androgen treatment. We confirmed that TGF-${\beta}1$ secretion is increased by androgen treatment in DP-6, whereas androgen-inducible TGF-${\beta}1$ was significantly suppressed by the ROSscavenger, N-acetyl cysteine. Therefore, we suggest that induction of TGF-${\beta}1$ by androgen is mediated by ROS in hair follicle DPCs.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.572-580
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• 2016

3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

• Korean Journal of Pharmacognosy
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• v.51 no.1
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• pp.41-48
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• 2020

This study was conducted to evaluate the effects of Padina arborescens and 1-O-myristoyl-2-O-oleoyl-3-O-(α-D-glucopyranosyl)-glycerol(MOGG), its active component, on the prevention of hair loss. The P. arborescens extract and MOGG inhibited the activity of 5α-reductase, which converts testosterone to dihydrotestosterone(DHT), a main cause of androgenetic alopecia. When immortalized rat vibrissa dermal papilla cells were treated with MOGG, the proliferation of dermal papilla cells significantly increased. In addition, we found that the P. arborescens extract and MOGG could open the K_ATP channel, which may contribute to increase hair growth. Furthermore, MOGG promoted PGE₂ production in HaCaT cells. The results suggest that MOGG from the P. arborescens extract has the potential to treat alopecia via 5α-reductase inhibition, the proliferation of dermal papilla, the opening of the K_ATP channel and/or increase of PGE₂ production.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.118-124
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• 2012

This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of $5{\alpha}$-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted $PGE_2$ production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-${\alpha}$ production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, $5{\alpha}$-reductase inhibition, increase of $PGE_2$ production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.440-447
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• 2023

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/β-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/β-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of β-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/β-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.