In Vitro and In Vivo Models for the Development of Hair Growth Materials By Regulating the ß-Catenin Signaling Pathways.

Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of ß-catenin. We confirmed that 100 nM tegatrabetan (TG), a ß-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3ß and Akt, translocation of ß-catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, ß-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing ß-catenin-mediated hair growth.

Examining the Effect of Notocactus ottonis Cold Vacuum Isolated Plant Cell Extract on Hair Growth in C57BL/6 Mice Using a Combination of Physiological and OMICS Analyses.

The biological and psychological importance of hair is recognized worldwide. Molecules that can promote the activation of hair follicle stem cells and the initiation of the growth phase have been subjects of research. Clarifying how hair regeneration is regulated may help to provide hair loss treatments, including cosmetic and even psychological interventions. We examined the hair-growing effects of a cell extract (CE) obtained from cactus Notocactus ottonis by the cold vacuum extraction protocol, by investigating its hair-growing effects, relevant mechanisms, and potential factors therein. Using male C57BL/6 mice, vehicle control (VC: propylene glycol: ethanol: water), MXD (minoxidil, positive control), and N. ottonis CE (N-CE, experimental) were applied topically to the backs of mice. The results showed that MXD and N-CE were more effective in promoting hair growth than VC. An increase in number of hair follicles was observed with N-CE in hematoxylin-eosin-stained skin tissue. The metabolite composition of N-CE revealed the presence of growth-promoting factors. Using mouse back whole-skin tissue samples, whole-genome DNA microarray (4 × 44 K, Agilent) and proteomics (TMT-based liquid chromatography-tandem mass spectrometry) analyses were carried out, suggesting the molecular factors underlying hair-promoting effects of N-CE. This study raises the possibility of using the newly described N. ottonis CE as a hair-growth-promoting agent.

Vitamins and their derivatives synergistically promote hair shaft elongation ex vivo via PlGF/VEGFR-1 signalling activation.

BACKGROUND: Although vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, and pyridoxine, have been widely used in topical hair care products, their efficacy and mode of action have been insufficiently studied. OBJECTIVE: To elucidate the biological influence of Vits on hair follicles and determine the underlying mechanisms. METHODS: A mouse vibrissa hair follicle organ culture model was utilized to evaluate the effects of Vits on hair shaft elongation. Gene and protein expression analyses and histological investigations were conducted to elucidate the responsible mechanisms. A human hair follicle cell culture was used to assess the clinical relevance. RESULTS: In organ culture models, the combination of panthenyl ethyl ether, tocopherol acetate, and pyridoxine (namely, PPT) supplementation significantly promoted hair shaft elongation. PPT treatment enhanced hair matrix cell proliferation by 1.9-fold compared to controls, as demonstrated by Ki67-positive immunoreactivity. PPT-treated mouse dermal papillae exhibited upregulated Placental growth factor (Plgf) by 1.6-fold compared to controls. Importantly, the addition of PlGF neutralizing antibodies to the ex vivo culture diminished the promotive effect on hair growth and increase in VEGFR-1 phosphorylation achieved by PPT. A VEGFR-1 inhibitor also inhibited the promotion of hair growth. Microarray analysis suggested synergistic summation of individual Vits' bioactivity, putatively explaining the effect of PPT. Moreover, PPT increased PlGF secretion in cultured human dermal papilla cells. CONCLUSION: Our findings suggested that PPT promoted hair shaft elongation by activating PlGF/VEGFR-1 signalling. The current study can shed light on the previously underrepresented advantage of utilizing Vits in hair care products.

Methionine can subside hair follicle development prejudice of heat-stressed rex rabbits.

In the present experiment, we study the function of methionine on hair follicle development in heat-stressed Rex Rabbits and its potential molecular mechanism. Rex rabbits were randomly divided into 5 groups (30 replicates per group): control group (20-25°C, fed basic diet), heat stress group (30-34°C, fed basic diet), heat stress + methionine group (30-34°C, fed 0.15% methionine in addition to the basic diet). fed basic diet (control), heat stress + methionine group (30-34°C, fed 0.3% methionine in addition to the basic diet), heat stress + methionine group (30-34°C, fed 0.45% methionine in addition to the basic diet). The results show that heat stress decreases the hair follicle density of Rex rabbits, and the diet methionine addition significantly increases the hair follicle density of heat-stressed Rabbits (p < .05). Heat stress increased serum HSP70 concentration and skin HSP70 gene expression, 0.15%-0.3% methionine but not 0.45% addition alleviated the effect of heat stress. Dietary 0.15% methionine addition significantly increases the gene expression of Wnt10b, ß-catenin, LEF, FZD4, LRP6, Shh, HGF, EGF, and Noggin in heat-stressed Rex rabbits and observably decreases the gene expression of BMP2/4 and TGFb. There was no significant effect of methionine on the expression of IGF1 and FGF5/7 gene expression. In conclusion, methionine maybe promotes hair follicle development via TGFß-BMP/Shh-Noggin, Wnt10b/ß-catenin, EGF, and HGF signaling pathways in heat-stressed rabbits.

An extract of Leontopodium alpinum inhibits catagen development ex vivo and increases hair density in vivo.

OBJECTIVES: Hair loss and reduction in hair volume are hallmarks of hair disorders, such as telogen effluvium, or male or female pattern hair loss, and hair ageing, which can cause severe distress in both men and women. Common anti-hair loss drugs carry some side effects; therefore, novel, safer approaches targeting milder phenotypes are highly advocated. In this context, we investigated an extract of the alpine plant Edelweiss, Leontopodium alpinum var. Helvetia, for its ability to modulate hair follicle (HF) growth ex vivo and inhibit hair loss while increasing hair regeneration in vivo. METHODS: Human amputated HFs were microdissected from three donors, two women and one man, and cultured ex vivo for 6 days. After treatment with 0.001% Edelweiss extract (EWDE), we investigated hair shaft production and anagen/catagen conversion, and measured known parameters associated with hair growth, that is hair matrix keratinocyte proliferation and apoptosis, dermal papilla inductivity, and growth factors, by quantitative (immuno)histomorphometry. To assess the anti-hair loss potential of the alpine plant compound, we performed a randomized, placebo-controlled human study enrolling Caucasian women and men, aged 18 to 65 years, with normal hair loss. After 5 months' daily use of an extract containing leave-on serum, we analysed hair density and anagen-to-catagen/telogen ratio by the Trichogram analysis. RESULTS: Our results revealed a significant prolongation in the anagen phase in HFs treated with 0.001% Edelweiss, as indicated by an increase in HFs remaining in anagen and a significant decrease in hair cycle score. In line with this effect, EWDE significantly stimulated hair matrix (HM) keratinocyte proliferation, and dermal papilla inductivity, as shown by a significant up-regulation of versican expression and alkaline phosphatase activity, and a tendential increase in FGF7 immunoreactivity in the dermal papilla of all HFs or only anagen VI HFs. Corroborating the ex vivo results, we observed a significant increase in growing hair shaft numbers (hair density) after treatment with Edelweiss extract formulation, and a tendential up-regulation in the anagen-to-catagen/telogen ratio. CONCLUSIONS: We show here, through several lines of evidence, that the selected extract of the alpine plant Leontopodium alpinum var Helvetia (Edelweiss) inhibits premature catagen induction, possibly by stimulating dermal papilla inductivity. It is therefore worth exploiting this extract clinically as an anti-hair loss agent, both for preventing ageing-associated hair shedding and as an adjuvant therapy for hair loss disorders.

OBJECTIFS: La perte de cheveux et la réduction du volume des cheveux sont caractéristiques des troubles capillaires, tels que l'effluvium télogène, ou la calvitie chez l'homme ou la femme, et le vieillissement des cheveux, qui peuvent causer une certaine détresse chez les hommes et les femmes. Les médicaments courants contre la chute des cheveux ont des effets secondaires, par conséquent, de nouvelles approches plus sûres ciblant des phénotypes légers sont fortement recommandées. Dans ce contexte, nous avons étudié un extrait de la plante alpine Edelweiss, Leontopodium alpinum var. Helvetia, pour sa capacité à stimuler la croissance du follicule pileux (HF) ex vivo et à inhiber la chute des cheveux tout en augmentant la régénération des fibres capillaires in vivo. MÉTHODES: Les follicules pileux (HF) humains prélevés ont été microdisséqués chez trois donneurs, deux femmes et un homme, et cultivés ex vivo pendant 6 jours. Après le traitement avec l'extrait d'Edelweiss à 0,001 % (EWDE), nous avons étudié la production de fibre capillaire et la conversion anagène/catagène, ainsi que mesuré les paramètres connus associés à la croissance des cheveux, à savoir, la prolifération des kératinocytes dans la matrice capillaire et l'apoptose, l'induction des papilles dermiques, et des facteurs de croissance, par (immuno-)histomorphométrie quantitative. Pour évaluer le potentiel des propriétés anti-chute du cheveu de l'extrait de plante alpine, nous avons réalisé une étude clinique aléatoire avec placebo, sur des femmes et des hommes de type caucasien âgés de 18 à 65 ans présentant une perte de cheveux normale. Après cinq mois d'utilisation quotidienne d'un sérum sans rinçage contenant l'extrait de plante, nous avons analysé la densité capillaire et le rapport anagène à catagène/télogène par trichogramme. RÉSULTATS: Nos résultats ont révélé une prolongation significative de la phase anagène dans les HF traités avec 0,001% d'Edelweiss, comme l'indique une augmentation des HF restant en phase anagène et une diminution significative du « hair cycle score ¼. En ligne avec cet effet, EWDE a stimulé de façon significative la matrice du cheveux (HM), la prolifération des kératinocytes, et l'induction de la papille dermique, comme le montre une augmentation significative de l'expression du versican et de l'activité de la phosphatase alcaline, et une augmentation tendancielle de l'immunoréactivité FGF7 dans la papille dermique de tous les HF ou seulement des HF anagènes VI. Corroborant les résultats ex vivo, nous avons observé une augmentation significative du nombre de fibres capillaires (densité de cheveux) après le traitement avec la formulation d'extrait d'Edelweiss, et une augmentation tendancielle dans le rapport anagène à catagène/télogène. CONCLUSIONS: Nous montrons ici, à travers plusieurs éléments de preuve, que l'extrait sélectionné de la plante alpine Leontopodium alpinum var Helvetia (Edelweiss) inhibe l'induction prématurée de la phase catagène, en stimulant la papille dermique. Il est donc possible d'utiliser cet extrait comme un agent anti-chute, à la fois pour prévenir la chute des cheveux associée au vieillissement mais aussi comme une thérapie complémentaire pour les troubles liés à la perte des cheveux.

The effects of centipedegrass extract on hair growth via promotion of anagen inductive activity.

To investigate the CGE on hair growth and to explore the mechanism that is involved in the acceleration of anagen induction, we investigated the effects of CGE studied on cell proliferation and molecular mechanism in human hair dermal papilla cells (hDPCs) and keratinocytes (HaCaT cells). Additionally, hair growth evaluation was carried out following topical treatment of the dorsal skin of telogen C57BL/6 mice with CGE for 14 days. As result, CGE increased cell viability and ALP activity in hDPCs. Moreover, CGE increased the expression of catenin beta 1 (CTNNB1), ALP, sex-determining region Y-box 2 (SOX2), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor A (VEGFA) genes in hDPCs. CGE increased the expression of proteins such as ALP, ß-catenin, and phosphorylation of glycogen synthase kinase 3ß (pGSK3ß), and protein kinase B (pAKT) in hDPCs. Furthermore, CGE induced the proliferation of HaCaT cells and up-regulated AKT-ERK-GSKß-ß-catenin signaling in HaCaT cells. Additionally, the anagen induction effects of CGE were confirmed on the telogen-anagen transition mice model. these findings demonstrated that CGE promoted the entering the growth phase of hair follicle via activation of ß-catenin signaling pathways in vivo. Thus, this study suggests that CGE might be a potential therapeutic reagent for hair growth.

Regulation of Cytokines and Dihydrotestosterone Production in Human Hair Follicle Papilla Cells by Supercritical Extraction-Residues Extract of Ulmus davidiana.

This study was conducted to examine the anti-hair loss mechanism of the supercritical fluid extraction-residues extract of Ulmus davidiana by the regulation of cytokine production and hormone function in human dermal follicle papilla cells (HDFPCs). To investigate the modulatory effects on H2O2-induced cytokines, we measured transforming growth factor-beta and insulin-like growth factor 1 secreted from HDFPCs. To investigate the regulatory effects of supercritical extraction-residues extract of Ulmus davidiana on dihydrotestosterone hormone production, cells were co-incubated with high concentrations of testosterone. The supercritical extraction-residues extract of Ulmus davidiana significantly inhibited the secretion of transforming growth factor-beta but rescued insulin-like growth factor 1 in a dose-dependent manner. The supercritical extraction-residues extract of Ulmus davidiana markedly reduced dihydrotestosterone production. These results suggest that the supercritical fluid extract residues of Ulmus davidiana and their functional molecules are candidates for preventing human hair loss.

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

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.

Dexpanthenol Promotes Cell Growth by Preventing Cell Senescence and Apoptosis in Cultured Human Hair Follicle Cells.

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; ß-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-ß1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.

Hair Growth Stimulation Effect of Centipeda minima Extract: Identification of Active Compounds and Anagen-Activating Signaling Pathways.

Centipeda minima (L.) A. Braun & Asch is a well-studied plant in Chinese medicine that is used for the treatment of several diseases. A recent study has revealed the effects of extract of Cetipeda minima (CMX) standardized by brevilin A in inducing hair growth. However, the mechanism of action of CMX in human hair follicle dermal papilla cells (HFDPCs) has not yet been identified. We aimed to investigate the molecular basis underlying the effect of CMX on hair growth in HFDPCs. CMX induced the proliferation of HFDPCs, and the transcript-level expression of Wnt family member 5a (Wnt5a), frizzled receptor (FZDR), and vascular endothelial growth factor (VEGF) was upregulated. These results correlated with an increase in the expression of growth-related factors, such as VEGF and IGF-1. Immunoblotting and immunocytochemistry further revealed that the phosphorylation of ERK and JNK was enhanced by CMX in HFDPCs, and ß-catenin accumulated significantly in a dose-dependent manner. Therefore, CMX substantially induced the expression of Wnt signaling-related proteins, such as GSK phosphorylation and ß-catenin. This study supports the hypothesis that CMX promotes hair growth and secretion of growth factors via the Wnt/ß-catenin, ERK, and JNK signaling pathways. In addition, computational predictions of drug-likeness, together with ADME property predictions, revealed the satisfactory bioavailability score of CMX compounds, exhibiting high gastrointestinal absorption. We suggest that CMX could be used as a promising treatment for hair regeneration and minimization of hair loss.

Photobiomodulation therapy for hair regeneration: A synergetic activation of ß-CATENIN in hair follicle stem cells by ROS and paracrine WNTs.

Photobiomodulation therapy (PBMT) has shown encouraging results in the treatment of hair loss. However, the mechanism by which PBMT controls cell behavior to coordinate hair cycle is unclear. Here, PBMT is found to drive quiescent hair follicle stem cell (HFSC) activation and alleviate hair follicle atrophy. Mechanistically, PBMT triggers a new hair cycle by upregulating ß-CATENIN expression in HFSCs. Loss of ß-Catenin (Ctnnb1) in HFSCs blocked PBMT-induced hair regeneration. Additionally, we show PBMT-induced reactive oxygen species (ROS) activate the PI3K/AKT/GSK-3ß signaling pathway to inhibit proteasome degradation of ß-CATENIN in HFSCs. Furthermore, PBMT promotes the expression and secretion of WNTs in skin-derived precursors (SKPs) to further activate the ß-CATENIN signal in HFSCs. By contrast, eliminating ROS or inhibiting WNT secretion attenuates the activation of HFSCs triggered by PBMT. Collectively, our work suggests that PBMT promotes hair regeneration through synergetic activation of ß-CATENIN in HFSCs by ROS and paracrine WNTs by SKPs.

Micro-Current Stimulation Has Potential Effects of Hair Growth-Promotion on Human Hair Follicle-Derived Papilla Cells and Animal Model.

Recently, a variety of safe and effective non-pharmacological methods have been introduced as new treatments of alopecia. Micro-current electrical stimulation (MCS) is one of them. It is generally known to facilitate cell proliferation and differentiation and promote cell migration and ATP synthesis. This study aimed to investigate the hair growth-promoting effect of MCS on human hair follicle-derived papilla cells (HFDPC) and a telogenic mice model. We examined changes in cell proliferation, migration, and cell cycle progression with MCS-applied HFDPC. The changes of expression of the cell cycle regulatory proteins, molecules related to the PI3K/AKT/mTOR/Fox01 pathway and Wnt/ß-catenin pathway were also examined by immunoblotting. Subsequently, we evaluated the various growth factors in developing hair follicles by RT-PCR in MCS-applied (MCS) mice model. From the results, the MCS-applied groups with specific levels showed effects on HFDPC proliferation and migration and promoted cell cycle progression and the expression of cell cycle-related proteins. Moreover, these levels significantly activated the Wnt/ß-catenin pathway and PI3K/AKT/mTOR/Fox01 pathway. Various growth factors in developing hair follicles, including Wnts, FGFs, IGF-1, and VEGF-B except for VEGF-A, significantly increased in MCS-applied mice. Our results may confirm that MCS has hair growth-promoting effect on HFDPC as well as telogenic mice model, suggesting a potential treatment strategy for alopecia.

Activation of Hair Cell Growth Factors by Linoleic Acid in Malva verticillata Seed.

Hair loss by excessive stress from work and lifestyle changes has become a growing concern, particularly among young individuals. However, most drugs for alopecia impose a plethora of side effects. We have found the powerful impact of Malva verticillata seed extracts on alleviating hair loss. This study further isolated effective chemicals in M. verticillata seed extracts by liquid silica gel column chromatography. Under the screening for the growth rate (%) of human follicles dermal papilla cells (HFDPCs), we identified linoleic acid (LA) and oleic acid in n-hexane of M. verticillate (MH)2 fraction. LA treatment activated Wnt/ß-catenin signaling and induced HFDPCs growth by increasing the expression of cell cycle proteins such as cyclin D1 and cyclin-dependent kinase 2. LA treatment also increased several growth factors, such as vascular endothelial growth factor, insulin-like growth factor-1, hepatocyte growth factor, and keratinocyte growth factor, in a dose-dependent manner. Besides, LA significantly inhibited Dickkopf-related protein expression (DKK-1), a primary alopecia signaling by dihydrotestosterone. Our findings suggest that LA treatment may alleviate a testosterone-induced signaling molecule and induces HFDPCs growth by activating Wnt/ß-catenin signaling.

Ent-kaurane-type diterpenoids from Isodonis Herba activate human hair follicle dermal papilla cells proliferation via the Akt/GSK-3ß/ß-catenin transduction pathway.

A methanol extract from Isodonis Herba demonstrated significant proliferative effect on human hair follicle dermal papilla cells (HFDPC, % of control: 150.0 ± 2.0% at 20 µg/mL, p < 0.01). From the extract, 14 ent-kaurane-type diterpenoids (1-14), two abietane-type diterpenoids (15 and 16) and four triterpenoids (17-20) were isolated. Among the isolates, enmein (1, 160.9 ± 3.0% at 20 µM, p < 0.01), isodocarpin (2, 169.3 ± 4.9% at 5 µM, p < 0.01), nodosin (4, 160.5 ± 12.4% at 20 µM, p < 0.01), and oridonin (8, 165.4 ± 10.6% at 10 µM, p < 0.01) showed the proliferative effects. The principal component enmein (1) activated the expression of vascular endothelial growth factor (VEGF) mRNA, upregulated the production of VEGF and increased levels of phospho-Akt, phospho-GSK-3ß, and ß-catenin accumulation in HFDPC, which could be the mechanism of these activate proliferation activity.

The impact of skin massage frequency on the intrafollicular transport of silica nanoparticles: Validation of the ratchet effect on an ex vivo porcine skin model.

The human hair follicle (HF) represents a promising drug delivery target as an anatomical entity by itself, but also as a gateway enabling dermal or systemic bioavailability of active cosmetic and pharmaceutical ingredients. Due to its morphological characteristics, the HF provides a mechanically driven transport process of nanoparticles (NPs) when external forces are applied. This mechanism was presented as the so-called ratchet effect within the framework of an in silico study published recently. To investigate the influence of massage frequency on the penetration depth of NPs, and, by this, to validate the results obtained in silico, we implemented a corresponding application protocol on an ex vivo porcine skin model. In this connection, we compared three different skin massage frequencies (4.2 Hz, 50 Hz, 100 Hz) for the topical application of cyanine 5-labeled silica NPs (Cy5-SNPs). To elucidate the interplay of frequency and particle size, we furthermore applied Cy5-SNPs of three different diameters (300 nm, 676 nm, 1000 nm). Confocal laser scanning microscopy was utilized to investigate the follicular penetration depth of Cy5-SNPs on cryohistological slices. By this, we could demonstrate that the massage frequency and the follicular penetration depth exhibit an inverse relation pattern. Thus, the highest follicular penetration depth was observed within the 4.2 Hz group, while the lowest follicular penetration depth was found within the 100 Hz group for each Cy5-SNP size category. Additionally, we found that 676 nm Cy5-SNPs penetrated significantly deeper into HFs than 300 nm Cy5-SNPs and 1000 nm Cy5-SNPs, respectively. Summarizing, our results show that a low massage frequency including a dominant radial direction component leads to deeper follicular penetration depths of NPs than automated 3D-oscillation massage at 50 Hz or 100 Hz. Thus, our findings are in line with recent in silico results. Regarding translational purposes, our results are of high interest, since a massage executed at 250BPM (4.2 Hz) is within a realizable range for manual application, e.g. for the implementation into clinical routines or the domestic use of drugs or cosmetics. Furthermore, the application of different massage frequencies offers the opportunity of patho-specific targeting as different anatomical parts of the HF can be reached.

Dietary Eriodictyon angustifolium Tea Supports Prevention of Hair Graying by Reducing DNA Damage in CD34+ Hair Follicular Keratinocyte Stem Cells.

Hair follicular keratinocyte stem cells (HFKSC) which provide a functional niche for melanocyte stem cells (MSC) are the primary target of hair graying. However, little research has been done on anti-hair graying medicines targeting HFKSC. We focused on Eriodictyon angustifolium (Ea), which reduces human hair graying when applied topically. To investigate the protective effect of dietary Ea tea (EaT) on hair pigmentation, we used an acute mouse model of hair graying that mimics X-ray-induced DNA damage associated with age-related hair graying. Our results suggest that dietary EaT maintained the niche HFKSC function against X-ray-induced DNA damage and hair graying. These results indicate that dietary EaT may prevent age-related hair graying and serve as an anti-hair graying herbal medicine.

Study on the chemical constituents of nut oil from Prunus mira Koehne and the mechanism of promoting hair growth.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunus mira Koehne (P. mira, Tibetan name: ཁམབུ།) is a kind of medicinal plant commonly used in Tibetan areas. The classic Tibetan medicine book Jingzhu Materia Medica records that "the nut oil from P. mira is used to cure loss of hair, eyebrows, beards, etc." but the clinical experience has not been explored. Hair loss (alopecia) is a skin disease that becomes a common concern in Chinese society since it affects the appearance of a person. This paper studies the effectiveness of nut oil from P. mira in promoting hair growth and its working mechanism. MATERIALS AND METHODS: The content of different components in the nut oil from P. mira was determined by HPLC. Two hair removal methods (sodium sulfide and hair removal cream) were used to study the effect of different doses on hair growth in KM mice. Then select the effective group, and use C57BL/6 mice to determine the number of hair follicles, dermal thickness, ß-catenin, GSK3ß and Wnt10 b mRNA and protein expression. RESULTS: The contents of α-tocopherol, ß-sitosterol, Vitamin E, Oleic acid and linoleic acid in nut oil from P. mira growing in 12 different regions were determined by HPLC. The linearity reached 0.999. The RSD of precision, stability, repeatability, and sample recovery was less than 3%. The dose-effect relationship suggested that 30.13 and 14.07 mg medicinal material·(cm2·d)-1 oil promoted hair growth and the dose effect was positively correlated. 30.13 mg medicinal material·(cm2·d)-1 nut oil from P. mira can accelerate hair follicles into the anagen, increasing Wnt 10 b mRNA expression, ß-catenin mRNA and protein expression, and GSK-3 ß protein expression. CONCLUSION: This study improved the quality control of nut oil from P. mira and found that it has the effect of promoting hair growth in mice. The working mechanism may be related to Wnt/ß-catenin signaling pathway.

Pigmentation Effect of Rice Bran Extract in Hair Follicle-Like Tissue and Organ Culture Models.

BACKGROUND: Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury and determines the hair and skin color. Melanin has the ability to block ultraviolet radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. Hence, various approaches have been proposed to increase the synthesis of melanin. METHODS: The current study aimed to develop a three-dimensional hair follicle-like tissue (HFLT) model with human dermal papilla, melanocytes, and outer root sheaths cells. This model showed enhanced melanogenesis-related protein expression after rice bran ash extract (RBE) treatment. Next, we investigated the melanogenic effect of RBE in the HFLT and compared the results to those of hair follicle (HF) organ culture model. RESULTS: RBE was found to significantly increase the expression of microphthalmia-associated transcription factor, a key transcription factor involved in melanin production, in both HFLT and organ culture models. Results showed that melanogenesis-related protein expression levels were higher in the RBE group compared to those in the control group. Similar results were obtained by immunohistochemistry. CONCLUSION: Our data suggested that RBE promotes melanin biosynthesis. Taken together, this simple in vitro HFLT model system has the potential to provide significant insights into the underlying molecular mechanisms of HF melanogenesis, and hence can be used for controlled evaluation of the efficacy of new materials for melanogenesis.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.