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.

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.

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.

Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract.

Camellia japonica L. is a flowering tree with several medicinal and cosmetic applications. Here, we investigated the efficacy of C. japonica placenta extract (CJPE) as a potential therapeutic agent for promotion of hair growth and scalp health by using various in vitro and in vivo assays. Moreover, we performed transcriptome analysis to examine the relative expression of human follicle dermal papilla cells (HFDPC) in response to CJPE by RNA-sequencing (RNA-seq). In vitro assays revealed upregulation of the expression of hair growth marker genes in HFDPC after CJPE treatment. Moreover, in vivo clinical tests with 42 adult female participants showed that a solution containing 0.5% CJPE increased the moisture content of the scalp and decreased the scalp's sebum content, dead scalp keratin, and erythema. Furthermore, RNA-seq analysis revealed key genes in HFDPC which are associated with CJPE. Interestingly, genes associated with lipid metabolism and cholesterol efflux were upregulated. Genes upregulated by CJPE are associated with several hormones, including parathyroid, adrenocorticotropic hormone, α-melanocyte-stimulating hormone (alpha-MSH), and norepinephrine, which are involved in hair follicle biology. Furthermore, some upregulated genes are associated with the regulation of axon guidance. In contrast, many genes downregulated by CJPE are associated with structural components of the cytoskeleton. In addition, CJPE suppressed genes associated with muscle structure and development. Taken together, this study provides extensive evidence that CJPE may have potential as a therapeutic agent for scalp treatment and hair growth promotion.

Feature-Based Molecular Networks Identification of Bioactive Metabolites from Three Plants of the Polynesian Cosmetopoeia Targeting the Dermal Papilla Cells of the Hair Cycle.

The term cosmetopoeia refers to the use of plants in folks' cosmetics. The aerial parts of Bidens pilosa L., the leaves of Calophyllum inophyllum L. and the fruits of Fagraea berteroana A.Gray ex Benth are traditionally used in French Polynesia for hair and skin care. During the hair cycle, dermal papilla cells and their interaction with epithelial cells are essential to promote hair follicle elongation. The aim of our investigations was the identification of metabolites from these three plants and chemical families responsible for their hair growth activity. A bioactivity-based molecular network was produced by mapping the correlation between features obtained from LC-MS/MS data and dermal papilla cell proliferation, using the Pearson correlation coefficient. The analyses pointed out glycosylated flavonols and phenolic acids from B. pilosa and C. inophyllum, along with C-flavonoids, iridoids and secoiridoids from F. berteroana, as potential bioactive molecules involved in the proliferation of hair follicle dermal papilla cells. Our results highlight the metabolites of the plant species potentially involved in the induction of hair follicle growth and support the traditional uses of these plants in hair care.

Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.

Hair Growth Activity of Three Plants of the Polynesian Cosmetopoeia and Their Regulatory Effect on Dermal Papilla Cells.

Hair loss is becoming increasingly prevalent as dietary and living habits change. The search for natural products to limit hair loss has led to tapping into traditional cosmetic knowledge. We studied three plants of the Polynesian cosmetopoeia, Bidens pilosa, Calophyllum inophyllum and Fagraea berteroana, to determine their ability to promote hair growth. Their chemical content was characterized by liquid chromatography coupled to mass spectrometry (LC-MS). Their proliferative activity on dermal papilla cells (DPCs) was assessed via MTT assay and molecular targets were evaluated by RT-qPCR analysis of seven factors involved in the modulation of the hair cycle, CCND1, LEF1, DKK1, WNT5A PPARD, TGFΒ1, PPARD and RSPO2. Our results show that our extracts significantly increased proliferation of dermal papilla cells. Furthermore, LC-MS/MS analysis revealed a diversity of molecules, flavonoids, iridoids and organic acids, some known for hair-inducing properties. Finally, specific extracts and fractions of all three plants either upregulated CCND1, LEF1 and PPARD involved in stimulating hair follicle proliferation and/or lowered the gene expression levels of hair growth inhibiting factors, DKK1 and TGFB1. Our findings suggest that extracts from B. pilosa, C. inophyllum and F. berteroana are interesting candidates to stimulate hair growth.

Hair growth potential of Salvia plebeia extract and its associated mechanisms.

Context: Although Salvia plebeia (SP) R. Brown (Labiatae) is known to possess various biological activities, the effects of SP on hair growth have not been elucidated.Objective: To investigate the hair growth potential of SP extract by using human dermal papilla cells (hDPCs) and C57BL/6 mice.Materials and methods: The entire SP plant sample was ground into powder and extracted with 99.9% methyl alcohol. Various concentrations of SP extract were added to hDPCs to evaluate the proliferation, migration, and factors related to hair growth and cycling. Effect of topical SP administration on hair regrowth was tested in vivo in male C57BL/6 mice for 21 days.Results: SP extract significantly increased the proliferation of cultured hDPCs at doses of 15.6 and 31.3 µg/mL compared to control group by 123% and 132%, respectively. Expression of hepatocyte growth factor increased while the level of TGF-ß1 and SMAD2/3 decreased when treated with SP extract. At the molecular level, the extract activated Wnt/ß-catenin signalling by raising ß-catenin and phospho-GSK3ß expression. SP extract also exerted anti-apoptotic and proliferative effects in hDPCs by increasing the Bcl-2/Bax ratio and activating cell proliferation-related proteins, ERK and Akt. Finally, the extract caused an induction of the anagen phase leading to significantly enhanced hair growth in treated male mice.Discussion and conclusion: Our results indicate that SP extract has the capacity to activate hDPCs into a proliferative state to promote hair growth. Further research is necessary to determine the bioactive components and their mechanisms of action responsible for SP-related hair growth effect.

Induction of Hair Keratins Expression by an Annurca Apple-Based Nutraceutical Formulation in Human Follicular Cells.

Hair disorders may considerably impact the social and psychological well-being of an individual. Recent advances in the understanding the biology of hair have encouraged the research and development of novel and safer natural hair growth agents. In this context, we have previously demonstrated-at both preclinical and clinical level-that an Annurca apple-based dietary supplement (AMS), acting as a nutraceutical, is endowed with an intense hair-inductive activity (trichogenicity), at once increasing hair tropism and keratin content. Herein, in the framework of preclinical investigations, new experiments in primary human models of follicular keratinocytes and dermal papilla cells have been performed to give an insight around AMS biological effects on specific hair keratins expression. As well as confirming the biocompatibility and the antioxidant proprieties of our nutraceutical formulation, we have proven an engagement of trichokeratins production underlying its biological effects on human follicular cells. Annurca apples are particularly rich in oligomeric procyanidins, natural polyphenols belonging to the broader class of bioflavonoids believed to exert many beneficial health effects. To our knowledge, none of the current available remedies for hair loss has hitherto shown to stimulate the production of hair keratins so clearly.

The peptide AC 2 isolated from Bacillus-treated Trapa japonica fruit extract rescues DHT (dihydrotestosterone)-treated human dermal papilla cells and mediates mTORC1 signaling for autophagy and apoptosis suppression.

The Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).

Hair Growth Promoting Effect of Hottuynia cordata Extract in Cultured Human Hair Follicle Dermal Papilla Cells.

Houttuynia cordata (HC) is a traditional oriental herbal medicinal plant widely used as a component of complex prescriptions in Asia for alopecia treatment. The effect of HC on hair growth and its underlying mechanism, however, have not been demonstrated or clarified. In this study, we investigated the hair growth promoting effect of HC in cultured human dermal papilla cells (hDPCs). HC extract was found to stimulate the proliferation of hDPCs and this stimulation might be in part a consequence of activated cellular energy metabolism, because treatment of HC extract increased the generation of nicotinamide adenine dinucleotide (NADH) and ATP through increasing the mitochondrial membrane potential (ΔΨ). In the context of cell cycle, HC extract increased the expression of CDK4 and decreased the expression of CCNA2 and CCNB1, implying that HC extract might induce G1 phase progression of DPCs which resulted in enhanced proliferation. HC extract increased the expression of Bcl2 essential for maintaining hair follicle anagen stage and cell survival. On the contrary, the expression of p16 and p21 was down-regulated by HC extract. In addition, HC extract enhanced the secretion of platelet-derived growth factor (PDGF)-aa and vascular endothelial growth factor (VEGF) and induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Furthermore, HC extract prolonged anagen stage in organ cultured human hair follicles. Our data strongly suggest that HC extract could support hair growth by stimulating proliferation of DPCs and elongating anagen stage, resulted from enhanced cellular energy metabolism and modulation of gene expression related to cell cycle, apoptosis, and growth factors.

NANOG Alleviates the Damage of Human Hair Follicle Mesenchymal Stem Cells Caused by H2O2 through Activation of AKT Pathway.

OBJECTIVE: To explore the protective effect of NANOG against hydrogen peroxide (H2O2) -induced cell damage in the human hair follicle mesenchymal stem cells (hHF-MSCs). METHODS: NANOG was expressed from a lentiviral vector, pLVX-IRES-ZsGreen. NANOG hHF-MSCs and vector hHF-MSCs were treated with 400 µmol/L hydrogen peroxide (H2O2) for 2 h, the cell survival rate, cell morphology, ROS production, apoptosis and expression of AKT, ERK, and p21 were determined and compared. RESULTS: Our results showed that NANOG could activate AKT and upregulate the expression of p-AKT, but not p-ERK. When treated with 400 µmol/L H2O2, NANOG hHF-MSCs showed higher cell survival rate, lower ROS production and apoptosis, higher expression of p-AKT, higher ratio of p-AKT/AKT. CONCLUSION: Our results suggest that NANOG could protect hHF-MSCs against cell damage caused by H2O2 through activating AKT signaling pathway.

Bacillus/Trapa japonica Fruit Extract Ferment Filtrate enhances human hair follicle dermal papilla cell proliferation via the Akt/ERK/GSK-3ß signaling pathway.

BACKGROUND: Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, creating a need for new treatments to control hair loss and prevent balding. Treatments based on plant-derived compounds could potentially prevent hair loss. Human hair follicle dermal papilla (HDP) cells, a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions such as androgenic alopecia. We examined the effect of Bacillus/Trapa japonica fruit ferment filtrate extracts (TJFs) on HDP cells to determine whether activation of the Akt/ERK/GSK-3ß signaling pathway improved HDP cell proliferation. METHODS: We prepared TJFs using various methods. The extract properties were analyzed using WST-1, Lowry, and cell migration assays as well as immunofluorescence staining. We also determined the cell cycle stage and performed western blotting and an in ovo chick chorioallantoic membrane assay. Last, we constructed an organotypic three-dimensional cell culture model for immunohistochemical use. RESULTS: Our study confirmed that the TJFs contained numerous peptides and five unknown fractions. The TJFs stimulated HDP cell proliferation and migration via the Akt/ERK/GSK-3ß signaling pathway. To verify that the Akt/ERK/GSK-3ß pathway affected HDP cell proliferation, we treated HDP cells with LY294002 (an Akt inhibitor), BIO (a GSK-3ß inhibitor), and PD98059 (an ERK inhibitor). The TJFs also induced cell cycle progression, inhibited type І 5α-reductase, decreased apoptosis, and enhanced angiogenesis (vascular expansion). In addition to these signaling pathways, proteins including insulin-like growth factor-1 and keratinocyte growth factor, stimulating hair growth, were detected in the three-dimensional cell culture model. CONCLUSIONS: Our results confirmed that TJFs enhance HDP cell proliferation via the Akt/ERK/GSK-3ß signaling pathway, suggesting a potential treatment for alopecia.

The mechanism of activated platelet-rich plasma supernatant promotion of hair growth by cultured dermal papilla cells.

BACKGROUND: Platelet-rich plasma (PRP) is an innovative treatment of androgenic alopecia in the early stages of development, and its mechanism of action is not well investigated. OBJECTIVE: The objective was to investigate the promotion of hair growth by activated PRP supernatant in cultured dermal papilla cells (DPCs). METHODS AND MATERIALS: Human DPCs were isolated and grown in culture with or without activated PRP supernatant. The expression of phosphorylated growth factor receptors (GFRs) in cultured DPCs was assayed by immunofluorescence and Western blotting. Signal pathways mediated by GFRs were identified by a human phosphokinase array. RESULTS: Activated PRP supernatant enhanced the expression of phosphorylated fibroblast growth factor receptor (FGFR)-1, platelet-derived growth factor receptor (PDGFR)α, and PDGFRß in cultured DPCs. Activated PRP supernatant activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways that promoted proliferation of DPCs. Downregulation of glycogen synthase kinase-3 was consistent with the involvement of Wnt signaling. Activated PRP supernatant increased the hair growth promoting ability of DPCs by activating the Wnt signaling pathway. CONCLUSION: Autologous activated PRP supernatant promoted signaling in cultured human DPCs via pathways known to be involved in hair growth. The results warrant further study of PRP for the clinical treatment of androgenic alopecia.

Evaluating hair growth promoting effects of candidate substance: A review of research methods.

Androgenetic alopecia (AGA) is the most common form of hair loss disorder. As the prevalence of AGA rises, the demand for AGA treatments is rising accordingly, prompting research to identify therapeutic candidates to treat AGA. Because AGA is caused by crosstalk among multiple hair follicle (HF) cell components, understanding the effects of candidate molecules on HF cells is essential to determining therapeutic candidates for treatment. To date, research has centered on HF dermal papilla and outer root sheath cells and has indicated that the hair growth effects of candidate substances may be mediated via alterations in several signaling pathways and signature genes in these HF cells. In more integrative evaluations, the HF unit is used as an ex vivo organ culture model to verify the effects of therapeutic candidates. Animal models have also been used to evaluate the effects of candidate substances. The main outcomes used to evaluate the effects of candidate substances are 1) changes in HF growth rates in vitro, 2) anagen induction capabilities, and 3) the effects of androgen modulation. This article reviews a series of methods used to evaluate the hair growth-promoting effects of candidate substances, providing an overview of cell assays, organs, and animal models used in AGA research in order to facilitate AGA research moving forward.

Lanostane-type triterpenes from the sclerotium of Inonotus obliquus (Chaga mushrooms) as proproliferative agents on human follicle dermal papilla cells.

Chaga mushrooms, the sclerotium of Inonotus obliquus, have been used in Mongolia as a traditional hair shampoo to maintain healthy hair. Bioassay-guided fractionations of the extract of Chaga mushrooms using a proliferation assay on human follicle dermal papilla cells (HFDPCs) gave five lanostane-type triterpenes (1-5), whose structures were identified by spectroscopic evidence. Among these, lanosterol (1), inotodiol (3), lanost-8,24-diene-3ß,21-diol (4), and trametenolic acid (5) demonstrated proproliferative effects on HFDPCs more potent than minoxidil, an anti-alopecia agent, used as the positive control. The lanostane-type triterpenes (1, 3, 4, and 5) appeared to be potential candidates of new agents possibly used for hair-care with a stimulative effect on hair growth.

Serenoa repens and N-acetyl glucosamine/milk proteins complex differentially affect the paracrine communication between endothelial and follicle dermal papilla cells.

Current treatments for hair follicle (HF) disruption are based on 5-α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens ( SR) and N-acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both SR and NAG/Lac-induced endothelial tubulogenesis were enhanced by FDPC. SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by SR, was further augmented by FDPC. In FDPC 5-α reductase-II and ß-catenin expressions were modified by SR and less by NAG/Lac, with no additional effect by HMVEC. SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1ß production. Finally, SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.

From stem cells protection to skin microbiota balance: Orobanche rapum extract, a new natural strategy.

BACKGROUND: Healthy skin is a delicate balance between skin renewal and microbiota homeostasis, and its imbalance promotes premature aging and dermatological disorders. Skin stem cells are key actors in this process but their sensitivity to aging and external stressors such as UV reduces the skin renewal power. The skin microbiota has been recently described as active in the healthy skin, and its imbalance could trigger some disorders. AIMS: We hypothesized that reactivation of stem cells and maintenance of microbiota could be a disruptive strategy for younger and healthier skin. We thus developed a new plant extract that restores the entire skin renewal process by sequential activation from stem cells stimulation to microbiota protection. METHODS: We studied stem cells comportment in the presence of Orobanche rapum extract by survivin immunocytochemistry and caspases 3 and 9 dosages. We also analyzed epidermal differentiation markers by immunohistochemistry and lipids organization by GC/MS At the clinical level, we investigated the impact of O. rapum extract on microbiota and on skin aspect. RESULTS: We demonstrated an active protection of skin stem cells through the maintenance of their clone-forming capacity and resistance to UV through the overexpression of survivin coupled to caspases inhibition. Furthermore, we showed the restoration of epidermal differentiation markers and ceramide biosynthesis favorable to orthorhombic organization. Clinical studies, including microbiota analysis, showed an active skin surface renewal coupled with microbiota protection. CONCLUSION: We evidenced that our active ingredient is able to stimulate skin rejuvenation while protecting the cutaneous microbiota, creating healthier skin and thereby beauty.

Effects of all-trans retinoic acid on goat dermal papilla cells cultured in vitro

Background: All-trans retinoic acid (ATRA), a vitamin A-derived active metabolite, exerts important functions in hair biology. Previous studies indicated that excess ATRA hampered hair follicle morphogenesis and cyclic regeneration in adulthood, but other studies stated that ATRA promoted hair growth. Dermal papilla (DP), a cluster of specialized fibroblasts, plays pivotal roles in controlling development and regeneration of hair follicle. Several lines of evidence indicated that DP might be the target cells of ATRA in the hair follicle. To confirm this hypothesis, the present study was performed to explore the biological effects of ATRA on goat dermal papilla cells (DPCs) and clarify the roles of ATRA in hair biology. Results: Our experimental results indicated that key signaling transducers of ATRA were dynamically expressed in distinct stages of goat cashmere growth cycle, and high-dose ATRA treatment (10-5 M) significantly impaired the viability of goat DPCs and lowered the ratio of proliferating cells. Otherwise, goat DPCs were stimulated to enter apoptosis and their cell cycle progression was severely blocked by ATRA. Moreover, the expression of fibroblast growth factor 7 (Fgf7), one of the potent hair growth stimulators secreted by DPCs, was transcriptionally repressed following ATRA treatment. Conclusion: DPCs are the targets of ATRA in the hair follicle, and ATRA negatively regulates hair growth by the targeted suppression of cell viability and growth factor expression of goat DPCs. Through these observations, we offer a new mechanistic insight into the roles of ATRA in hair biology.

Baicalin increases hair follicle development by increasing canonical Wnt/ß­catenin signaling and activating dermal papillar cells in mice.

Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/ß­catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3ß degradation complex, leading to accumulation of ß­catenin and activation of Wnt/ß­catenin signaling. In addition, baicalin was observed to increase the alkaline phosphatase levels in dermal papillar cells, a process which was dependent on Wnt pathway activation. Given its non­toxicity and ease of topical application, baicalin represents a promising treatment for alopecia and other forms of hair loss. Further studies of baicalin using human hair follicle transplants are warranted in preparation for future clinical use.