Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner (p<0.05), and 100 ppm of DA-5512 and 1 μM minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group (p<0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p<0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD (p<0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

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Nature-derived lignan compound VB-1 exerts hair growth-promoting effects by augmenting Wnt/β-catenin signaling in human dermal papilla cells

PeerJ ◽

10.7717/peerj.4737 ◽

2018 ◽

Vol 6 ◽

pp. e4737 ◽

Cited By ~ 8

Author(s):

Jieshu Luo ◽

Mengting Chen ◽

Yingzi Liu ◽

Hongfu Xie ◽

Jian Yuan ◽

...

Keyword(s):

Hair Growth ◽

Dermal Papilla ◽

Hair Shaft ◽

Cell Counting ◽

Dependent Manner ◽

Rt Pcr ◽

Concentration Dependent Manner ◽

Dermal Papilla Cells ◽

Growth Promoting

Background Vitexin is a kind of lignan compound which has been shown to possess a variety of pharmacological effects, such as anti-inflammatory, anti-oxidative and anti-cancer activities. However the effect of vitexin on hair regeneration has not been elaborated. Methods The proliferation of human dermal papilla cells (hDPCs) was examined by cell counting and continuous cell culture after vitexin compound 1 (VB-1) was treated. The expression of lef1, wnt5a, bmp2, bmp4, alpl and vcan was examined by RT-PCR. The expression of dkk1, tgf-β1, active-β-Catenin, and AXIN2 was examined by RT-PCR or immunoblotting. Hair shaft growth was measured in the absence or presence of VB-1. Results We demonstrated that VB-1 significantly promotes the proliferation of hDPCs in a concentration-dependent manner within a certain concentration range. Among the hair growth-related genes investigated, dkk1 was clearly down-regulated in hDPCs treated with VB-1. The increased active β-Catenin and decreased AXIN2 protein levels suggest that VB-1 facilitates Wnt/β-catenin signaling in hDPCs in vitro. The expression of DP signature genes was also upregulated after VB-1 treatment. Our study further indicated that VB-1 promotes human hair follicle (HF) growth by HF organ culture assay. Discussion VB-1 may exert hair growth-promoting effects via augmenting Wnt/β-catenin signaling in hDPCs.

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Tectoridin Stimulates the Activity of Human Dermal Papilla Cells and Promotes Hair Shaft Elongation in Mouse Vibrissae Hair Follicle Culture

Molecules ◽

10.3390/molecules27020400 ◽

2022 ◽

Vol 27 (2) ◽

pp. 400

Author(s):

Gary Ka-Wing Yuen ◽

Bryan Siu-Yin Ho ◽

Lish Sheng-Ying Lin ◽

Tina Ting-Xia Dong ◽

Karl Wah-Keung Tsim

Keyword(s):

Hair Growth ◽

Nuclear Translocation ◽

Ethanolic Extract ◽

Dermal Papilla ◽

Hair Shaft ◽

Herbal Extract ◽

Dependent Manner ◽

Dermal Papilla Cells ◽

Growth Promoting ◽

Screening Platform

To search hair growth-promoting herbal extract, a screening platform of having HEK293T fibroblast being transfected with pTOPFLASH DNA construct was developed over a thousand of herbal extracts and phytochemicals were screened. One of the hits was ethanolic extract of Rhizoma Belamcandae, the rhizome of Belamcanda chinensis (L.) DC. Tectoridin, an isoflavone from Rhizoma Belamcandae, was shown to be responsible for this activation of promoter construct, inducing the transcription of pTOPFLASH in the transfected fibroblasts in a dose-dependent manner. The blockage by DKK-1 suggested the action of tectoridin could be mediated by the Wnt receptor. The hair growth-promoting effects of tectoridin were illustrated in human follicular dermal papilla cells and mouse vibrissae organ cultures. In tectoridin-treated dermal papilla cultures, an activation of Wnt signaling was demonstrated by various indicative markers, including TCF/LEF1 transcriptional activity, nuclear translocation of β-catenin, expressions level of mRNAs encoding axin-related protein, (AXIN2), β-catenin, lymphoid enhancer-binding factor-1 (LEF-1), insulin-like growth factor 1 (IGF-1) and alkaline phosphatase (ALP). In addition, an increase of hair shaft elongation was observed in cultured mouse vibrissae upon the treatment of tectoridin. Tectoridin, as well as the herbal extract of Rhizoma Belamcandae, possesses hair promoting activity, which deserves further development.

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In Vitro Hair Growth Promoting Effect of a Noncrosslinked Hyaluronic Acid in Human Dermal Papilla Cells

BioMed Research International ◽

10.1155/2021/5598110 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Nicola Zerbinati ◽

Sabrina Sommatis ◽

Cristina Maccario ◽

Maria C. Capillo ◽

Serena Di Francesco ◽

...

Keyword(s):

Hyaluronic Acid ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

In Vitro Assays ◽

Promoting Effect ◽

Dermal Papilla Cells ◽

Clinical Investigations ◽

Endothelial Growth Factor

Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations.

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Hormones and Hair Growth: Variations in Androgen Receptor Content of Dermal papilla Cells Cultured from Human and Red Deer (Cervus Elaphus) Hair Follicles.

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12363039 ◽

1993 ◽

Vol 101 (s1) ◽

pp. 114S-120S ◽

Cited By ~ 24

Author(s):

Valerie Anne Randall ◽

Margaret Julie Thornton ◽

Andrew Guy Messenger ◽

Nigel Andrew Hibberts ◽

Andrew Stewart Irving Loudon ◽

...

Keyword(s):

Androgen Receptor ◽

Cervus Elaphus ◽

Hair Growth ◽

Red Deer ◽

Dermal Papilla ◽

Hair Follicles ◽

Dermal Papilla Cells ◽

Cells Cultured

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Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro

Journal of Cell Science ◽

10.1242/jcs.99.3.627 ◽

1991 ◽

Vol 99 (3) ◽

pp. 627-636 ◽

Cited By ~ 2

Author(s):

C.A. Jahoda ◽

A.J. Reynolds ◽

C. Chaponnier ◽

J.C. Forester ◽

G. Gabbiani

Keyword(s):

Smooth Muscle ◽

Hair Follicle ◽

Dermal Papilla ◽

Hair Follicles ◽

Dermal Papilla Cells ◽

Smooth Muscle Alpha Actin ◽

Actin Expression ◽

Alpha Actin ◽

Sheath Cells

We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing.

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HERBAL CREAMS OF REISHI EXTRACT AND TEA TREE OIL FOR HIRSUTISM–AN IN VIVO STUDY

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i5.39781 ◽

2020 ◽

pp. 106-110

Author(s):

SANGEETA CHOUDHURY ◽

BLR MADHAVI

Keyword(s):

Topical Application ◽

Hair Growth ◽

Ethanolic Extract ◽

Hair Follicles ◽

In Vivo Studies ◽

Control Group ◽

Tea Tree Oil ◽

Tea Tree

Objective: The aim of this work to formulate, evaluate and compare the effectiveness of herbal creams containing extract of reishi and tea tree oil for treating hirsutism. Methods: Herbal ingredients were authenticated. Cream base was initially formulated. Three formulations of herbal cream were prepared. Reishi ethanolic extract, tea tree oil, and combination of tea tree oil and reishi extract were added to the cream base and formulated cream were named as RHC, THC and RTC respectively. In vitro evaluations on herbal creams were done for the physicochemical characteristics. In vivo studies were carried out on female Swiss Albino mice for the activity against hair growth by topical application of cream to shaved skin. The histological and morphometric evaluation was carried out. Skin irritancy study was conducted. Results: The herbal creams showed desirable physicochemical properties like pH, viscosity and spreadability. Statistical analysis for the length of hair was performed by using one way ANOVA followed by DUNNET’S post hoc test where THC and RTC were found to be significant whereas RHC showed no significant reduction of hair growth compared to control. RTC showed a significant effect at p<0.05 and hair growth reduction was significant for THC at p<0.001 compared to the control group. RTC and THC showed mild to moderate reduction in the size of the hair follicles with a reduction of sebaceous gland size in the histological analysis. Conclusion: Topical application of herbal creams to mice showed that hair growth was fastest in group RHC and was slowest in group THC and intermediate with RTC. It can be concluded that these herbal actives can be used as an effective treatment against hirsutism. Within the study period, tea tree oil was found to be more effective than reishi extract and the combination product. Further formulation studies and in vivo studies need to be carried out on reishi to assess its effectiveness against hirsutism.

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Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

International Journal of Molecular Sciences ◽

10.3390/ijms21165672 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5672

Author(s):

Kyung-Eun Ku ◽

Nahyun Choi ◽

Jong-Hyuk Sung

Keyword(s):

Hair Growth ◽

Expression Patterns ◽

Dermal Papilla ◽

Hair Follicles ◽

Hair Cycle ◽

Outer Root Sheath ◽

Dermal Papilla Cells ◽

Root Sheath ◽

Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

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“Two-Cell Assemblage” Assay: A Simple in vitro Method for Screening Hair Growth-Promoting Compounds

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.581528 ◽

2020 ◽

Vol 8 ◽

Author(s):

Sunhyae Jang ◽

Jungyoon Ohn ◽

Bo Mi Kang ◽

Minji Park ◽

Kyu Han Kim ◽

...

Keyword(s):

Stem Cell ◽

Hair Growth ◽

Large Scale ◽

Cell Activation ◽

Imaging System ◽

Control Group ◽

Dependent Manner ◽

Growth Promoting ◽

Axis Length

Alopecia arises due to inadequate hair follicle (HF) stem cell activation or proliferation, resulting in prolongation of the telogen phase of the hair cycle. Increasing therapeutic and cosmetic demand for alleviating alopecia has driven research toward the discovery or synthesis of novel compounds that can promote hair growth by inducing HF stem cell activation or proliferation and initiating the anagen phase. Although several methods for evaluating the hair growth-promoting effects of candidate compounds are being used, most of these methods are difficult to use for large scale simultaneous screening of various compounds. Herein, we introduce a simple and reliable in vitro assay for the simultaneous screening of the hair growth-promoting effects of candidate compounds on a large scale. In this study, we first established a 3D co-culture system of human dermal papilla (hDP) cells and human outer root sheath (hORS) cells in an ultra-low attachment 96-well plate, where the two cell types constituted a polar elongated structure, named “two-cell assemblage (TCA).” We observed that the long axis length of the TCA gradually increased for 5 days, maintaining biological functional integrity as reflected by the increased expression levels of hair growth-associated genes after treatment with hair growth-promoting molecules. Interestingly, the elongation of the TCA was more prominent following treatment with the hair growth-promoting molecules (which occurred in a dose-dependent manner), compared to the control group (p < 0.05). Accordingly, we set the long axis length of the TCA as an endpoint of this assay, using a micro confocal high-content imaging system to measure the length, which can provide reproducible and reliable results in an adequate timescale. The advantages of this assay are: (i) it is physiologically and practically advantageous as it uses 3D cultured two-type human cells which are easily available; (ii) it is simple as it uses length as the only endpoint; and (iii) it is a high throughput system, which screens various compounds simultaneously. In conclusion, the “TCA” assay could serve as an easy and reliable method to validate the hair growth-promoting effect of a large volume of library molecules.

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Wnt10b promotes hair follicles growth and dermal papilla cells proliferation via Wnt/β-Catenin signaling pathway in Rex rabbits

Bioscience Reports ◽

10.1042/bsr20191248 ◽

2020 ◽

Vol 40 (2) ◽

Cited By ~ 4

Author(s):

Zhenyu Wu ◽

Yanli Zhu ◽

Hongli Liu ◽

Gongyan Liu ◽

Fuchang Li

Keyword(s):

Cell Cycle ◽

Signaling Pathway ◽

Cell Cycle Progression ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Dermal Papilla Cells ◽

Root Sheath ◽

Inner Root Sheath

Abstract Wnt signaling plays an important role in the growth and development of hair follicles (HFs). Among the signaling molecules, Wnt10b was shown to promote the differentiation of primary skin epithelial cells toward the hair shaft and inner root sheath of the HF cells in mice in vitro. Whisker HFs were isolated from Rex rabbits and cultured in vitro to measure hair shaft growth. Meanwhile, dermal papilla cells (DPCs) were isolated and cultured in vitro. Treatment with AdWnt10b or the Wnt/β-Catenin Pathway inhibitor, XAV939, assessed the DPCs proliferation by CCK-8 assay. And the cell cycle was also analyzed by flow cytometry. We found that Wnt10b could promote elongation of the hair shaft, whereas XAV-939 treatment could eliminated this phenomenon. AdWnt10b treatment promoted the proliferation and induced G1/S transition of DPCs. AdWnt10b stimulation up-regulated β-Catenin protein in DPCs. Inhibition of Wnt/β-Catenin signaling by XAV-939 could decreased the basal and Wnt10b-enhanced proliferation of DPCs. And could also suppress the cell cycle progression in DPCs. In summary, our study demonstrates that Wnt10b could promote HFs growth and proliferation of DPCs via the Wnt/β-Catenin signaling pathway in Rex rabbits.

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