• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.933-941
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• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.168-177
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• 2020

Background: Ginseng has been widely used as a health-promoting tonic. Gintonin present in ginseng acts as a lysophosphatidic acid (LPA) receptor ligand that activates six LPA receptor subtypes. The LPA6 subtype plays a key role in normal hair growth, and mutations in the LPA6 receptor impair normal human hair growth. Currently, human hair loss and alopecia are concerning issues that affect peoples' social and day-to-day lives. Objective: We investigated the in vitro and in vivo effects of a gintonin-enriched fraction (GEF) on mouse hair growth. Methods: Human hair follicle dermal papilla cells (HFDPCs) and six-week-old male C57BL/6 mice were used. The mice were divided into the four groups: control, 1% minoxidil, 0.75% GEF, and 1.5% GEF. The dorsal hair was removed to synchronize the telogen phase. Each group was treated topically, once a day, for 15 days. We analyzed hair growth activity and histological changes. Results: GEF induced transient [Ca²⁺]_i, which stimulated HFDPC proliferation and caused 5-bromo-2'-deoxyuridine (BrdU) incorporation in a concentration-dependent manner. GEF-mediated HFDPC proliferation was blocked by the LPA receptor antagonist and Ca²⁺ chelator. HFDPC treatment with GEF stimulated vascular endothelial growth factor release. Topical application of GEF and minoxidil promoted hair growth in a dose-dependent manner. Histological analysis showed that GEF and minoxidil increased the number of hair follicles and hair weight. Conclusion: Topical application of GEF promotes mouse hair growth through HFDPC proliferation. GEF could be one of the main components of ginseng that promote hair growth and could be used to treat human alopecia.

• Journal of Life Science
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• v.29 no.4
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• pp.455-460
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• 2019

In previous studies, we confirmed the effective antimicrobial activity of fermented Dendropanax morbifera leaf/branch extracts with Lactobacillus plantarum ilchiwhangchil 1785 and Lactobacillus plantarum ilchiwhangchil 2020. In this study, we investigated the hair growth effect of D. morbifera leaf/branch extracts fermented with L. plantarum ilchiwhangchil 1785 and L. plantarum ilchiwhangchil 2020 on human hair dermal papilla cells. The growth rate of human hair dermal papilla cells treated with fermented extracts in the range of 1 to $10{\mu}g/ml$ significantly increased in a concentration-dependent manner, without increasing cell death. Double staining studies showed that the growth of cells treated with fermented D. morbifera leaf/branch extracts was more active than that of control cells. Moreover, the cells treated with the fermented D. morbifera leaf/branch extracts exhibited a 18.84% and 23.31% increase in cell mobility, respectively, as compared with that of the untreated cells. High-performance liquid chromatography (HPLC) was used to determine the active agents responsible for hair growth. The results showed that the content of ${\beta}$-sitosterol, which is known to affect hair growth, increased about 10 times in the fermentation process of D. morbifera leaf/branch extracts. Taken together, the findings confirm that fermented Dendropanax morbifera leaf/branch extracts promote hair growth.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.3
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• pp.167-172
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• 2017

In this study, we investigated the effect of Puerariae Radix ethanol extracts (EPR). The effect of the EPR on proliferation of human hair dermal papilla cells(HHDPCs) by MTT assay and observed Expression of mechanisms that regulate cell proliferation extracellular signal-regulated kinase(ERK) and Akt by western blot. The results showed EPR increased the proliferation of HHDPCs and up-regulation phosphorylation of ERK and Akt. ERK and Akt increased by EPR inhibited phosphorylation by PD98059 (ERK inhibitor) and LY294002 (Akt inhibitor), and cell proliferation was also inhibited. These results suggested EPR increases the proliferation of HHDPCs through phosphorylation of ERK and Akt, and therefore is a beneficial effect for the alopecia treatment.

• BMB Reports
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• v.45 no.4
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• pp.253-258
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• 2012

The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically-validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.

• Journal of Life Science
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• v.33 no.3
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• pp.234-241
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• 2023

At present, many countries around the world are legalizing cannabis and its products, and research on various treatments using cannabis is being actively conducted. However, the cannabis plant contains other compounds whose biological effects have not yet been established. We investigated the effect of cannabidiol (CBD) on hair growth in human dermal papilla cells (HDPCs). 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of CBD. The HDPCs viability of CBD was examined via water-soluble tetrazolium salt (WST-1) assay. The expression of hair-loss-related markers in HDPCs by CBD treatment was analyzed by real-time PCR and western blotting. The DPPH, ABTS radical scavenging activity assay showed that CBD had superior antioxidant activities. In HDPCs, CBD increased cellular proliferation at concentrations without cytotoxicity. It also increased the expressions of fibroblast growth factor 1 (FGF1), fibroblast growth factor 7 (FGF7), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF). These results correlated with a decrease in the expression of inhibition-related factors, such as androgen receptor (AR) and transforming growth factor beta 1 (TGF-B1). Moreover, CBD resulted in a significant increase in the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). Therefore, it is suggested that CBD may be a potential remedy for the treatment of alopecia.

• Korea Journal of Cosmetic Science
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• v.1 no.1
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• pp.11-18
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• 2019

Caffeine is widely used in cosmetics and hair care products. Although its efficacy in stimulating hair growth has been confirmed in recent studies, its mechanism of action remains unelucidated. The present study aimed to determine the effects of caffeine on hair growth, with a focus on intracellular hair follicle activity. Experiments included in vitro and ex vivo tests, and a clinical study. Caffeine enhanced the cellular activity and potassium channel opening. It also promoted human hair follicle elongation. Immunohistochemical staining showed that the Ki-67 signal was significantly higher in cells treated with caffeine. These efficacies of caffeine were comprehensively demonstrated in clinical results, wherein caffeine-containing shampoo improved hair density after 24 weeks of testing. Collectively, the results of this study demonstrated that caffeine promoted hair growth and inhibited the progression of hair loss by enhancing intracellular activity of hair follicles.

• The Korea Journal of Herbology
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• v.39 no.1
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• pp.23-29
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• 2024

Objectives : Polyporus umbellatus is a medicinal mushroom that has been used for over thousands years in Chinese medicine as a powerful diuretic to relieve fluid retention and edema. Dermal papilla is located at the bottom of the hair follicle and connected to the blood vessels where it gets the nutrients and oxygen to nurture hair follicle. This study examined the mechanism through which the ethanol extract of Polyporus umbellatus (EPU) promoted the proliferation of human dermal papilla cells (HHDPCs). Methods : To estimate the proliferative effects of EPU on HHDPCs, cell viability was estimated by thiazolyl blue tetrazolium bromide (MTT) assay. Western blotting was used to investgate the activation of ERK, phosphoinositide 3-kinase (PI3K)/Akt, β-catenin, GSK-3β and heme oxygenase-1 (HO-1). Cells were treated with inhibitors of ERK and Akt prior to EPU treatment. Results : EPU promoted the proliferation of HHDPCs and the phosphorylation of ERK and Akt in dose dependent manner. However, the proliferative effect of EPU on HHDPCs was inhibited by pre-treatment of ERK inhibitor (PD98059) and Akt inhibitor (LY294002). Furthermore, EPU respectively stimulated the protein expression of β-catenin and phosphorylated GSK-3β. EPU significantly increased the protein expression levels of proliferation and cytoprotection related genes such as Bcl-2, SIRT-1, and HO-1 in cells. Conclusion : This results suggest that EPU promoted the proliferation of HHDPCs via activating PI3K/Akt and Wnt/β-catenin signaling pathway in HHDPCs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.671-680
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• 2017

This study was conducted to examine the effects and potential mechanisms of action of black soybean extracts and fermented black soybean extracts by Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animals subsp. lactis BB-12 (BB-12) on proliferation of human follicle dermal papilla cells (HFDPC). We examined changes in pH, total polyphenol, sugar, and reducing sugar contents according to fermentation period of black soybean extracts. Assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was performed to determine cell toxicity levels of the four black soybean extracts [black soybean water extract (BWE), black soybean ethanol extract (BEE), fermented BWE (F-BEW), and fermented BEE (F-BEE)]. Changes in mRNA expression levels of hair growth promoting factors and hair growth inhibiting factors by the four black soybean extracts were measured by real-time PCR. In addition, phosphorylation levels of mitogen-activated protein kinase family proteins were measured by western blot analysis. As a result, fermentation of black soybeans significantly reduced pH, total polyphenols, and sugar/reducing sugar contents. All four black soybean extracts showed no cellular toxicity in HFDPC. In fact, BEE significantly enhanced cell viability of HFDPC at $100{\mu}g/mL$ compared to control. BWE, BEE, and BWE-F significantly increased mRNA expression of vascular endothelial growth factor, and all four extracts increased mRNA expression of fibroblast growth factor. However, mRNA expression levels of apoptosis-related genes were not affected by black soybean extracts in HFDPC. Furthermore, BWE, BEE, and BWE-F significantly increased phosphorylation levels of extracellular signal-regulated kinase compared to control. Taken together, we demonstrated that black soybean extracts enhanced proliferation of human follicle dermal papilla cells partially via activation of hair growth promoting factors, although no particular significant effects on proliferation were observed by fermentation of black soybeans.