The detection of apoptosis and bcl2 in isolated secondary mohair follicles (growing and quiescent), cultured in vitro in the presence or absence of biotin

Apoptosis is a physiologically active process whereby cells die in a programmed manner (Stenn et al 1993). Growth of hair occurs as a consequence of proliferation and differentiation of the epidermal cells in the bulb of the hair follicles. Reduction of hair growth or loss of follicle viability may arise from reduction in proliferation, and also from apoptosis of epidermal hair shaft-forming cells. Increases in apoptosis have been associated with reduction in expression of the apoptosis inhibitor bcl2 (Lindner et al 1997). Previous studies (Tahmasbi et al 1998) have shown that biotin deficiency reduced the viability of mohair follicles and thymidine uptake in vitro. The aim of this work was to investigate the presence of apoptosis and bcl2 in follicles which maintained growth or were quiescent following culture in media unsupplemented or supplemented with biotin.

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CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth

Biochemical Journal ◽

10.1042/bcj20160466 ◽

2016 ◽

Vol 473 (19) ◽

pp. 3291-3305 ◽

Cited By ~ 4

Author(s):

Linli Zhou ◽

Kun Yang ◽

April Carpenter ◽

Richard A. Lang ◽

Thomas Andl ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Proliferation And Differentiation ◽

Wnt Ligands ◽

Epithelial Compartment ◽

Hair Follicle Growth

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.

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Annurca Apple Polyphenols Protect Murine Hair Follicles from Taxane Induced Dystrophy and Hijacks Polyunsaturated Fatty Acid Metabolism toward β-Oxidation

Nutrients ◽

10.3390/nu10111808 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1808 ◽

Cited By ~ 8

Author(s):

Gennaro Riccio ◽

Eduardo Sommella ◽

Nadia Badolati ◽

Emanuela Salviati ◽

Sara Bottone ◽

...

Keyword(s):

Fatty Acid ◽

Hair Loss ◽

Hair Growth ◽

Treatment Options ◽

Pentose Phosphate ◽

Hair Follicles ◽

Common Side Effect ◽

Safe Alternative ◽

Polyphenolic Extract

Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols from Malus Pumila Miller cv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrial β-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward β-oxidation.

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Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.774583 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jawaria Iltaf ◽

Sobia Noreen ◽

Muhammad Fayyaz ur Rehman ◽

Shazia Akram Ghumman ◽

Fozia Batool ◽

...

Keyword(s):

In Silico ◽

Hair Growth ◽

De Novo ◽

Growth Promotion ◽

Hair Follicles ◽

Binding Energies ◽

Ficus Benghalensis ◽

Rp Hplc

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle’s anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss.

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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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Integrin-linked kinase is required for epidermal and hair follicle morphogenesis

The Journal of Cell Biology ◽

10.1083/jcb.200608125 ◽

2007 ◽

Vol 177 (3) ◽

pp. 501-513 ◽

Cited By ~ 73

Author(s):

Katrin Lorenz ◽

Carsten Grashoff ◽

Robert Torka ◽

Takao Sakai ◽

Lutz Langbein ◽

...

Keyword(s):

Hair Follicle ◽

Leading Edge ◽

Hair Shaft ◽

Hair Follicles ◽

Membrane Dynamics ◽

Epidermal Keratinocytes ◽

Outer Root Sheath ◽

Root Sheath ◽

Integrin Linked Kinase

Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal–dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers. The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4395638 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Jae Young Yu ◽

Biki Gupta ◽

Hyoung Geun Park ◽

Miwon Son ◽

Joon-Ho Jun ◽

...

Keyword(s):

Clinical Study ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

Herbal Extract ◽

Control Group ◽

Dependent Manner ◽

Ki 67 ◽

Dermal Papilla Cells

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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Human hair growth in vitro

Journal of Cell Science ◽

10.1242/jcs.97.3.463 ◽

1990 ◽

Vol 97 (3) ◽

pp. 463-471

Author(s):

M.P. Philpott ◽

M.R. Green ◽

T. Kealey

Keyword(s):

Hair Follicle ◽

Human Hair ◽

Subcutaneous Fat ◽

Hair Shaft ◽

Hair Follicles ◽

Anagen Hair ◽

Scalpel Blade ◽

Thymidine Autoradiography

We report for the first time the successful maintenance and growth of human hair follicles in vitro. Human anagen hair follicles were isolated by microdissection from human scalp skin. Isolation of the hair follicles was achieved by cutting the follicle at the dermo-subcutaneous fat interface using a scalpel blade. Intact hair follicles were then removed from the fat using watchmakers' forceps. Isolated hair follicles maintained free-floating in supplemented Williams E medium in individual wells of 24-well multiwell plates showed a significant increase in length over 4 days. The increase in length was seen to be attributed to the production of a keratinised hair shaft, and was not associated with the loss of hair follicle morphology. [methyl-3H]thymidine autoradiography confirmed that in vitro the in vivo pattern of DNA synthesis was maintained; furthermore, [35S]methionine labelling of keratins showed that their patterns of synthesis did not change with maintenance. The importance of this model to hair follicle biology is further demonstrated by the observations that TGF-beta 1 has a negative growth-regulatory effect on hair follicles in vitro and that EGF mimics the in vivo depilatory effects that have been reported in sheep and mice.

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