Macrophage-Stimulating Protein Promotes Hair Growth Ex Vivo and Induces Anagen from Telogen Stage Hair Follicles In Vivo

AbstractShikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.

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Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.582282 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qingmei Liu ◽

Xiangguang Shi ◽

Yue Zhang ◽

Yan Huang ◽

Kai Yang ◽

...

Keyword(s):

Stem Cell ◽

Hair Follicle ◽

Hair Growth ◽

Ex Vivo ◽

Cell Activity ◽

Hair Follicles ◽

Androgenetic Alopecia ◽

Pcr Analysis

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.

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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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Plakoglobin Suppresses Epithelial Proliferation and Hair Growth in Vivo

The Journal of Cell Biology ◽

10.1083/jcb.149.2.503 ◽

2000 ◽

Vol 149 (2) ◽

pp. 503-520 ◽

Cited By ~ 80

Author(s):

Emmanuelle Charpentier ◽

Robert M. Lavker ◽

Elizabeth Acquista ◽

Pamela Cowin

Keyword(s):

Hair Growth ◽

Cultured Cells ◽

Hair Follicles ◽

Tumor Formation ◽

Hair Cycle ◽

Epithelial Proliferation ◽

Desmosomal Cadherins ◽

Hair Follicle Cycle

Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein β-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of β-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH2-terminally truncated form of plakoglobin (ΔN80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999). Hair follicles from PG and ΔN80PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al. 1994). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.

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Formulation and Evaluation of Herbal Hair Gel Containing Fenugreek Seed Extract for Nourishment and Hair Growth

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst196416 ◽

2019 ◽

pp. 92-103

Author(s):

Suryawanshi Nishant C ◽

Vijayendra Swamy S. M. ◽

Nagoba Shivappa N. ◽

Wanje Vaijanti V.

Keyword(s):

Hair Loss ◽

Hair Growth ◽

Estrogen Therapy ◽

Hair Follicles ◽

Hormone Deficiency ◽

Gelling Agent ◽

Nutritional Deficiencies ◽

Topical Formulation ◽

Fenugreek Seed

The present study now a days many people face the major problem related to hair i.e. hair loss. There are many causes of hair loss physiological conditions, emotional or physical stress, nutritional deficiencies, hormonal disorders one of the due to hormone deficiency of estrogen. External administration of the estrogen could changes the hormonal cycle and increase cancer risk some natural alternative estrogen therapy can be found in the various plants containing natural products those having weak estrogen activity like Phyto-estrogen. Herbal drug has less side effects and more effective as comparative to synthetic drug. Phytoestrogen are competing with the estrogen by the binding to the estrogen receptor and produce estrogen effect, Phytoestrogen in the fenugreek seed. Family – Fabaceae Ethanolic extract of (Trigonella foenum-graecum) fenugreek seed prepared for the topical formulation of herbal hair gel formulation by using Carbopol 934 gelling agent, glycerin, pvp, methyl paraben, PEG, Triethanolamine Fenugreek was evaluated for its potency on hair growth activity by in vivo method. In vivo, study 2.5mg of fenugreek extract is used. That is applied on the shaved skin of mice to determine the length of hair and the different cyclic phase of hair follicles like anagen and s phases were will be grow after some time periods. From the study topical use of gel formulation were apply for 30 days .There are use of fenugreek extract containing gel formulation over the shaved skin of mice that shows the significant result by increase the hair growth. The prepared gel was characterized for their physicochemical constants, preliminary phyto-chemical analysis, quantitative analysis, Spread-ability, pH, viscosity, and stability study.

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Macrophage-Derived Extracellular Vesicle Promotes Hair Growth

Cells ◽

10.3390/cells9040856 ◽

2020 ◽

Vol 9 (4) ◽

pp. 856 ◽

Cited By ~ 5

Author(s):

Ramya Lakshmi Rajendran ◽

Prakash Gangadaran ◽

Chang Hoon Seo ◽

Mi Hee Kwack ◽

Ji Min Oh ◽

...

Keyword(s):

Growth Factor ◽

Hair Loss ◽

Hair Growth ◽

Keratinocyte Growth Factor ◽

Hair Shaft ◽

Hair Follicles ◽

Wnt Proteins ◽

Short Period ◽

Phosphorylated Akt

Hair loss is a common medical problem affecting both males and females. Dermal papilla (DP) cells are the ultimate reservoir of cells with the potential of hair regeneration in hair loss patients. Here, we analyzed the role of macrophage-derived Wnts (3a and 7b) and macrophage extracellular vesicles (MAC-EVs) in promoting hair growth. We studied the proliferation, migration, and expression of growth factors of human-DP cells in the presence or absence of MAC-EVs. Additionally, we tested the effect of MAC-EV treatment on hair growth in a mouse model and human hair follicles. Data from western blot and flow cytometry showed that MAC-EVs were enriched with Wnt3a and Wnt7b, and more than 95% were associated with their membrane. The results suggest that Wnt proteins in MAC-EVs activate the Wnt/β-catenin signaling pathways, which leads to activation of transcription factors (Axin2 and Lef1). The MAC-EVs significantly enhanced the proliferation, migration, and levels of hair-inductive markers of DP cells. Additionally, MAC-EVs phosphorylated AKT and increased the levels of the survival protein Bcl-2. The DP cells treated with MAC-EVs showed increased expression of vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF). Treatment of Balb/c mice with MAC-EVs promoted hair follicle (HF) growth in vivo and also increased hair shaft size in a short period in human HFs. Our findings suggest that MAC-EV treatment could be clinically used as a promising novel anagen inducer in the treatment of hair loss.

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Cyclosporin A-loaded poly(d,l-lactide) nanoparticles: a promising tool for treating alopecia

Nanomedicine ◽

10.2217/nnm-2020-0089 ◽

2020 ◽

Vol 15 (15) ◽

pp. 1459-1469

Author(s):

Bruno Fernandes ◽

Teresa Matamá ◽

Andreia C. Gomes ◽

Artur Cavaco-Paulo

Keyword(s):

Cyclosporin A ◽

Ex Vivo ◽

Skin Permeation ◽

Hair Follicles ◽

Porcine Skin ◽

Skin Cell ◽

Promising Tool ◽

Physicochemical Stability ◽

New Strategy

Background: Alopecia treatments are scarce and lack efficacy. Cyclosporin A (CsA) has hair growth-inducing properties but its poor cutaneous absorption undermines its use in topical treatments. Aim: Development of a new potential topical treatment of alopecia with CsA. Materials & methods: CsA-loaded poly(d,l-lactide) (PLA) nanoparticles were obtained and characterized. Skin permeation was evaluated in ex vivo porcine skin. Results: Nanoparticles with good physicochemical stability increased CsA skin permeation/hair follicles accumulation, compared with a noncolloidal formulation. CsA biocompatibility in NCTC2455 keratinocytes (reference skin cell line) was clearly improved when encapsulated in PLA nanoparticles. Conclusion: This work fosters further in vivo investigation of CsA-loaded PLA nanoparticles as a promising new strategy to treat alopecia, a very traumatic, possibly autoimmune, disease.

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Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases

Pharmaceutics ◽

10.3390/pharmaceutics12121131 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1131 ◽

Cited By ~ 1

Author(s):

Rebekka Christmann ◽

Duy-Khiet Ho ◽

Jenny Wilzopolski ◽

Sangeun Lee ◽

Marcus Koch ◽

...

Keyword(s):

Targeted Delivery ◽

Drug Exposure ◽

Skin Diseases ◽

Kinase Inhibitor ◽

Ex Vivo ◽

Topical Therapy ◽

Hair Follicles ◽

Janus Kinase ◽

Inflammatory Skin Diseases

Tofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB’s safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles (NPs) can enhance targeted follicular drug delivery and minimize interfollicular permeation and thereby reduce systemic drug exposure. In this study, we report a facile method to assemble the stable and uniform 240 nm TFB loaded squalenyl derivative (SqD) nanoparticles (TFB SqD NPs) in aqueous solution, which allowed an excellent loading capacity (LC) of 20%. The SqD NPs showed an enhanced TFB delivery into HFs compared to the aqueous formulations of plain drug in an ex vivo pig ear model. Furthermore, the therapeutic efficacy of the TFB SqD NPs was studied in a mouse model of allergic dermatitis by ear swelling reduction and compared to TFB dissolved in a non-aqueous mixture of acetone and DMSO (7:1 v/v). Whereas such formulation would not be acceptable for use in the clinic, the TFB SqD NPs dispersed in water illustrated a better reduction in inflammatory effects than plain TFB’s aqueous formulation, implying both encouraging good in vivo efficacy and safety. These findings support the potential of TFB SqD NPs for developing a long-term topical therapy of AA.

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