• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.374-379
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• 2017

Hair loss affects interpersonal relationships and causes psychological stress. In this study, we investigated the antioxidant activity of Cynanchi Wilfordii Radix (CWR) and its effects on dermal papilla (DP) cells. Antioxidant efficacy was examined by ABTS assay. To confirm the effect on cell activity, MTS assay was performed and cell count was directly measured by hemocytometer. The mRNA expression of genes involved in hair formation and hair loss formation was confirmed by quantitative RT-PCR. CWR has a strong antioxidant activity. Cell viability of DP cells was increased to 118.5% by treatment of 0.5 mg/ml CWR for 24 hours, but the effect on the cell number was insignificant. These results suggest that CWR increases mitochondrial activity without promoting cell proliferation. Treatment of DP cells with 0.5 mg/ml CWR resulted in 48.5% reduction of mRNA expression of type 2 $5{\alpha}$-reductase, a major cause of male hair loss. In addition, mRNA expression of bone morphogenetic pretein (BMP), fibroblast growth factor (FGF)7, and FGF10, which are closely related to hair growth, was also decreased. Reactive oxygen species (ROS) acts as a cause of hair loss. The excellent antioxidant efficacy of CWR is thought to be able to effectively remove ROS. The dihydrotestosterone produced by type 2 $5{\alpha}$-reductase in DP cells is a potent inducer of male pattern hair loss. The inhibitory effect of type 2 $5{\alpha}$-reductase mRNA on DP cells induced by CWR may induce a positive therapeutic effect of male pattern hair loss.

• Journal of Life Science
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• v.27 no.11
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• pp.1269-1275
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• 2017

Tenebrio molitor samples were investigated as novel biomaterials and sources of food in several recent studies. However, the insects' effects on hair growth were not sufficiently researched. To develop novel and natural materials for preventing alopecia and promoting hair growth, this study investigated the antioxidant activities and hair-growth promotion effects of TMEs. To determine the antioxidant activities, the TMEs' DPPH radical- and nitrite-scavenging activities were examined. To determine hair-growth promotion effects, proliferations of human dermal papilla cells (DPCs) and the murine fibroblast cell line NIH3T3 were evaluated by using an MTS assay. In addition, estimations were made for cell viabilities against cell death induced by dihydrotesterone (DHT) in DPCs and inhibitory effects against potassium channel blocking induced by tolbutamide (TBM) in NIH3T3 cells. The DPPH radical scavenging activity was 81.17%, and the nitrite scavenging activity was 43.69%; the activities were similar to the activities of blueberry extracts. Moreover, the TMEs promoted the proliferation of human DPCs and NIH3T3 cells, which were concentrated dependently. The TMEs prevented not only DHT-induced DPC cytotoxicity but also TBM's action as a potassium channel blocker in NIH3T3 cells. The results suggested that TME could be used as a functional therapeutic alopecia reagent, to prevent hair loss and to promote hair growth.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.4
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• pp.385-392
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• 2022

In this study, keratin peptides were produced through high-temperature anaerobic fermentation of keratin, a protein contained in deer antler, with Fervidobacterium islandicum AW-1, and factors related to human hair, confirming the possibility of keratin peptides as cosmetic ingredients. As a result of the cytotoxicity and proliferation of deer antler fermented keratin peptide according to the concentration in the dermal papilla cell line, cytotoxicity was not observed and the cell proliferation effect was shown. For human dermal papilla cells, statistically significant increasing in growth factors according to the deer antler fermented keratin peptide was determined possiblity of effects on hair growth. Cosmetic products containing deer antler fermented keratin peptides were manufactured and skin safety and anti hair loss efficacy clinical tests were conducted. As a result, after 12 weeks of use, the total number of hairs statistically significant increased compared to before using the product and the difference in total number of hairs compared to the control group was found. In conclusion, we suggest that the possibility of fermented deer antler keratin peptide as a cosmeceutical ingredient as well as a health functional food material was confirmed.

• 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.

• Journal of Plant Biotechnology
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• v.49 no.4
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• pp.316-324
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• 2022

Hair loss causes psychological stress due to its effect on appearance. Therefore, the global market for hair loss treatment products is rapidly growing. The present study demonstrated that ginseng berry-derived and sequence-modified peptides promoted the proliferation rate of dermal papilla (DP) cells and keratinocytes, in addition to having antioxidant properties. Moreover, the potential role of these ginseng berry peptides as TGF-β2 antagonists was confirmed through in silico computer docking. In addition to promoting the growth of ,the ginseng berry-derived peptides also promoted the proliferation of keratinocytes experimental Particularly, an unmodified ginseng berry-derived peptide (GB-1) and two peptides with sequence modifications (GB-2 and GB-3) decreased ROS generation and exhibited a protective effect on damaged HaCaT keratinocytes. Computer-aided peptide discovery was conducted to identify the potential interactions of important proteins with transforming growth factor-beta 2 (TGF-β2), a key protein that plays a crucial role in the human hair growth cycle. Our results demonstrated that MAGH, an amino acid sequence present in herbal supplements and plant-based natural compounds, can inhibit TGF-β2.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.144-151
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• 2019

Alopecia has emerged as one of the biggest interests in modern society. Many studies have focused on the treatment of alopecia, such as transplantation of hair follicles or inhibition of the androgen pathway. Hair growth is achieved through proper proliferation of the components such as keratinocytes and dermal papilla cells (DPCs), movement, and interaction between the two cells. The present study examined the effect of the hedgehog (Hh) signaling pathway, which is an important and fundamental signal in the cell, on the morphology and the viability of human keratinocytes and DPCs. Upregulation of Hh signaling caused a morphological change and an increase in epithelium-mesenchymal transition-related gene expression but reduced the viability of keratinocytes, while the alteration of Hh signaling did not cause any change in DPCs. The results show the possibility that the regulation of Hh signaling can be applied for the treatment of alopecia.

• KSBB Journal
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• v.31 no.4
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• pp.237-245
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• 2016

Hair loss affects both men and women of all ages and often significantly affects social and psychologic health. Recent therapeutic approach for hair loss such as finasteride and minoxidil focused on regulation of hormonal system blood flow. However, long-term use of these drugs caused adverse effects. To develop herbal medicine for therapeutic effect on hair growth, here we screened the 10 medicinal herbs (Red ginseng, Licorice, Ulmus, Barberry root, Lycium root, Rehmanniae radix crudus, Sophora root, Sweet flag, Polygala root, Achyranthes) based on oriental medicine literature. We measured cytotoxicity, anti-oxidant activity, and $5-{\alpha}$ reductase inhibitory effect of the herbal medicine on human dermal papilla (DP) cells to investigate therapeutic effect of the herbal medicine. Treatment of the 1% herbal medicine did not show any cytotoxic effects, and cell growth was increased by treatment of the 0.1% herbal medicine. In addition, the herbal medicine showed stronger antioxidant activity than resveratrol and comparable inhibitory activity of $5-{\alpha}$ reductase with finasteride. Furthermore, when applied to in vivo mouse model, we also observed increases in the number and length of hair of the herbal medicine-treated group. These results suggest that the herbal medicine promotes hair growth by its antioxidant activity and inhibitory activity of $5-{\alpha}$ reductase and might therefore be a promising hair growth-promoting agent.

• Development and Reproduction
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• v.25 no.4
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• pp.279-291
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• 2021

Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient's psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.1
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• pp.75-85
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• 2023

This study was conducted to assess the effect of heptapeptide, composed of seven amino acids, on the activation of human hair cells isolated from human hair follicles. We have confirmed that the heptapeptide could bind to Lgr5 from the results of surface plasmon resonance (SPR) analysis. Heptapeptide enhanced the proliferation of human hair follicle dermal papilla cells (HHFDPCs) in a dose dependent manner. It induced the protein level of nuclear β-catenin, and the expressions of β-catenin downstream target genes, including LEF1, Cyc-D1 and c-Myc, in HHFDPCs. Heptapeptide significantly induced the phosphorylation of Akt and ERK, and the mRNA expressions of growth factors, including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), in HHFDPCs. In addition, heptapeptide significantly increased mRNA expression levels of differentiation-related transcription factors of human hair germinal matrix cells (HHGMCs) and differentiation markers of human hair outer root sheath cells (HHORSCs). Additionally, we investigated the effect of heptapeptide on human hair follicle stem cells (HHFSCs) differentiation and found that the heptapeptide reduced the mRNA and protein levels of stem cell markers, while it increased those levels of differentiation markers. These results have indicated that the heptapeptide promotes proliferation or differentiation of various types of hair follicle constituent cells through the induction of Wnt/β-catenin signaling. From the results, we have suggested that the heptapeptide in this study could be applied as a new functional material for the improvement of hair growth and alopecia.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.413-421
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• 2014

Corticotropin-releasing factor (CRF) is involved in the stress response and there is increasing evidence that stress influences skin disease such as hair loss. In cultured human hair follicles, CRF inhibits hair shaft elongation, induces premature regression and promotes the apoptosis of hair matrix keratinocytes. We investigated whether CRF influences the dermal papilla cells (DPC) that play pivotal roles in hair growth and cycling. Human DPCs were treated with CRF, adrenocorticotropic hormone (ACTH) and cortisol, key stress hormones along the hypothalamic-pituitary -adrenal (HPA) axis for 1-24 h. Interestingly, CRF modulated the expression of cytokines related to hair growth (KGF, Wnt5a, $TGF{\beta}-2$, Nexin) and increased cAMP production in cultured DPCs. CRF receptors were down-regulated by negative feedback systems. Pretreatment of CRF receptor antagonists or protein kinase A (PKA) inhibitor prevented the CRF-induced modulation. Since the CRF induces proopiomelanocortin (POMC) expression through the cAMP/PKA pathway, we analyzed POMC mRNA. CRF stimulated POMC expression in cultured human DPCs, yet we were unable to detect ACTH levels by western blot. These results indicate that CRF operates within DPCs through CRF receptors along the classical CRF signaling pathway and CRF receptor antagonists could serve as potential therapeutic and cosmetic agents for stress-induced hair loss.