Improvement of androgenic alopecia by extracellular vesicles secreted from hyaluronic acid-stimulated induced mesenchymal stem cells.

BACKGROUND: Androgenetic alopecia (AGA) is a common form of hair loss. Androgens, such as testosterone and dihydrotestosterone, are the main causes of AGA. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can reduce AGA. However, preparing therapeutic doses of MSCs for clinical use is challenging. Induced pluripotent stem cell-derived MSCs (iMSCs) are homogenous and easily expandable, enabling scalable production of EVs. Hyaluronic acid (HA) can exert various functions including free radical scavenging, immune regulation, and cell migration. Herein, we examined whether hyaluronic acid (HA) stimulation of iMSCs could produce EVs with enhanced therapeutic outcomes for AGA. METHODS: EVs were collected from iMSCs primed with HA (HA-iMSC-EVs) or without HA (iMSC-EVs). The characteristics of EVs were examined using dynamic light scattering, cryo-transmission electron microscopy, immunoblotting, flow cytometry, and proteomic analysis. In vitro, we compared the potential of EVs in stimulating the survival of hair follicle dermal papilla cells undergoing testosterone-mediated AGA. Additionally, the expression of androgen receptor (AR) and relevant growth factors as well as key proteins of Wnt/ß-catenin signaling pathway (ß-catenin and phosphorylated GSK3ß) was analyzed. Subsequently, AGA was induced in male C57/BL6 mice by testosterone administration, followed by repeated injections of iMSC-EVs, HA-iMSC-EVs, finasteride, or vehicle. Several parameters including hair growth, anagen phase ratio, reactivation of Wnt/ß-catenin pathway, and AR expression was examined using qPCR, immunoblotting, and immunofluorescence analysis. RESULTS: Both types of EVs showed typical characteristics for EVs, such as size distribution, markers, and surface protein expression. In hair follicle dermal papilla cells, the mRNA levels of AR, TGF-ß, and IL-6 increased by testosterone was blocked by HA-iMSC-EVs, which also contributed to the augmented expression of trophic genes related to hair regrowth. However, no notable changes were observed in the iMSC-EVs. Re-activation of Wnt/ß-catenin was observed in HA-iMSC-EVs but not in iMSC-EVs, as shown by ß-catenin stabilization and an increase in phosphorylated GSK3ß. Restoration of hair growth was more significant in HA-iMSC-EVs than in iMSC-EVs, and was comparable to that in mice treated with finasteride. Consistently, the decreased anagen ratio induced by testosterone was reversed by HA-iMSC-EVs, but not by iMSC-EVs. An increased expression of hair follicular ß-catenin protein, as well as the reduction of AR was observed in the skin tissue of AGA mice receiving HA-iMSC-EVs, but not in those treated with iMSC-EVs. CONCLUSIONS: Our results suggest that HA-iMSC-EVs have potential to improve AGA by regulating growth factors/cytokines and stimulating AR-related Wnt/ß-catenin signaling.

Panax notoginseng saponins loaded W/O microemulsion for alopecia therapy with panthenol as cosurfactant to reduce skin irritation.

The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of ß-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/ß-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.

Cedrol in ginger (Zingiber officinale) as a promising hair growth drug: The effects of oral and external administration on hair regeneration and its mechanism.

Ginger is an important cooking spice and herb worldwide, and scientific research has gradually confirmed the effect of ginger on preventing hair loss. Cedrol (CE) is a small sesquiterpene molecule in ginger and its external administration (EA) has shown hope in promoting hair growth, and alternative administration mode has become a potential treatment scheme to improve the efficacy of CE. The purpose of this study is to evaluate the effects of oral administration (OA) and EA of CE on hair regeneration of C57BL/6 alopecia areata (AA) mice induced by cyclophosphamide (CP) and to clarify the potential hair growth mechanism of CE in AA model in vitro and in vivo. The results showed that CE-OA has a shorter hair-turning black time and faster hair growth rate, and can lessen hair follicle damage induced by CP and promote hair follicle cell proliferation. Its effect is superior to CE-EA. At the same time, CE can increase the cytokines IFN-γ, IL-2, and IL-7 in the serum of mice, and decrease the expression of adhesion factors ICAM-1 and ELAM-1, thus alleviating the immunosuppression induced by CP. Mechanism research shows that CE regulates the JAK3/STAT3 signaling pathway, activates the Wnt3α/ß-catenin germinal center, and ameliorates oxidative stress induced by CP, thus promoting the proliferation of hair follicle cells and reversing AA. These results provide a theoretical basis for understanding the anti-AA mechanism of CE-OA, indicating that CE can be used as raw material for developing oral hair growth drugs.

The synergistic effect of phototherapy and active substances on hair growth.

Androgenic alopecia (AGA) typically manifests post-puberty, resulting in decreases in hair density, disruptions in the hair growth cycle, and alterations in hair follicle micro structure. Dihydrotestosterone (DHT) is a key hormone implicated in hair loss, especially on male. In this study, we found that each of arginine (Arg), arterial extract (AE) or biotin tripeptide-1 (BT-1), when combined with low level light therapy (LLLT, at 630 nm, 2 J/cm2), showed the efficacy in enhancing mitochondrial functions, cell proliferation and collagen synthesis in fibroblasts. Additionally, CARRIPOWER (the complexes of AE, BT-1, Arg, and Diaminopyrimidine derivatives), in conjunction with LLLT (630 nm, 2 J/cm2), showed promising results in dermal papilla cells (DPCs). The promising results contained not also inflammatory cytokines (IL-1ß and IL-6) and cell pro apoptotic factor (TGF-ß2) reduction, but also Wnt pathway inhibition by decreasing DKK1 level, and pro-hair growth factors (vascular endothelial growth factor (VEGF) and ß-catenin) increase. This innovative combination therapy offers a potential solution for the treatment of AGA, addressing both hormonal and cellular factors involved in hair loss.

Cellulose nanocrystal-stabilized Pickering emulsion gels as vehicles for follicular delivery of minoxidil.

Minoxidil (MXD) is the only topical over-the-counter medicine approved by the United States Food and Drug Administration for the treatment of androgenetic alopecia. For the purpose of targeting the delivery of MXD to dermal papilla in the hair follicle, MXD Pickering emulsion gels were fabricated based on the designability of deep eutectic solvent (DES) and the versatility of cellulose nanocrystal (CNC) and sodium carboxymethyl cellulose (CMC-Na). Structural studies and theoretical calculations results suggest that CNC can stabilize the interface between the MXD-DES and water, leading to the formation of Pickering emulsions. The rheological properties and stabilities of MXD Pickering emulsions were enhanced through gelation using CMC-Na, which highlights the good compatibility and effectiveness of natural polysaccharides in emulsion gels. Due to the particle size of emulsion droplets (679 nm) and the rheological properties of emulsion gel, the fabricated MXD formulations show in vivo hair regrowth promotion and hair follicle targeting capabilities. Interestingly, the MXD Pickering emulsion-based formulations exert therapeutic effects by upregulating the expression of hair growth factors. The proposed nanodrug strategy based on supramolecular strategies of CNC and CMC-Na provides an interesting avenue for androgenetic alopecia treatment.

Effects of Nannochloropsis salina Fermented Oil on Proliferation of Human Dermal Papilla Cells and Hair Growth.

The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H2O2-mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss.

Efficacy of type A botulinum toxin treatment for androgenetic alopecia using ultrasound combined with trichoscopy.

OBJECTIVE: This study aimed to assess the efficacy of type A botulinum toxin treatment for androgenetic alopecia (AGA) using a combination of ultrasound and trichoscopy. METHODS: Ninety patients with AGA who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to December 2022 were prospectively selected. These patients met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The alopecia severity in the male patients ranged between grades 2 and 4 on the Norwood-Hamilton Scale. The patients were randomly assigned to receive injections of the same type of biological agent in a double-blind manner, with injection sites being the vertex or bilateral temporal-frontal hairline. In this study, the botulinum toxin group comprised 72 patients who received a biological agent with 100 units of type A botulinum toxin. The control group included 18 patients, and the biological agent administered to them contained 0 units of type A botulinum toxin. The patients were observed using 22-MHz ultrasound and trichoscopy before treatment, and 1 month and 3 months after treatment to compare the differences in various parameters at the injection sites. The ultrasound parameters included average follicle width, length, and count. The trichoscopy parameters were the number of hairs within a 1-cm2 area on the counting scale. No artificial interventions were performed at the injection sites, and all examination conditions were consistent. RESULTS: The patients in the botulinum toxin group had wider and longer average follicle width and length at the vertex 1 month and 3 months after treatment (p < 0.05), and wider and longer average follicle width and length in the left frontal area 3 months after treatment (p < 0.05) compared with those in the control group. The average follicle width and length gradually increased after treatment in the botulinum toxin group (p < 0.05), but no statistically significant differences were found in the control group (p > 0.05). The patients in the botulinum toxin group exhibited greater average follicle lengths after treatment at the vertex compared with the left frontal area (p < 0.05). No statistically significant differences were found in follicle count (p > 0.05) or hair count (p > 0.05) between the botulinum toxin and control groups after injection treatment. CONCLUSIONS: The follicle width and length are effective parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA. Ultrasound revealed that the changes in follicles at the vertex occurred earlier than those in the left frontal area following treatment. Additionally, the changes in follicles were detected earlier than the changes in hair count using ultrasound. Ultrasound combined with trichoscopy provided more parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA, resulting in a more comprehensive evaluation.

Assessing the efficacy of mesotherapy products: Ultra Exo Booster, and Ultra S Line Plus in hair growth: An ex vivo study.

In this study, scalp tissues from Korean adults between 20 and 80 without skin disease were used. Scalp tissues were processed, and hair follicles were isolated and cultured with different treatments (including Bioscalp, Ultra Exo Booster, and Ultra S Line Plus) from Ultra V company. Over 12 days, observations and measurements of hair follicle characteristics were recorded at intervals (Days 0, 3, 6, 9, and 12). The study assessed the impact of these substances on hair follicle growth and morphology. Bioscalp, combined with Ultra Exo Booster and Ultra S Line Plus, showed significant hair elongation in ex vivo. Preservation of hair bulb diameter was observed, indicating potential for sustained hair growth by exosome-based products. The hair growth cycle analysis suggested a lower transition to the catagen stage in test products from Ultra V compared to non-treated groups. The research findings indicated that the tested formulations, especially the combination of Bioscalp, Ultra Exo Booster, and Ultra S Line Plus, demonstrated significant effectiveness in promoting hair growth, maintaining the integrity of the hair bulb, and reducing the transition to the catagen stage. The study suggests promising alternative treatments for hair loss, illustrating results that were as good as those of the conventional testing product groups.

Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne.

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

18-ß-Glycyrrhetinic Acid Promotes Hair Growth by Stimulating the Proliferation of Dermal Papilla Cells and Outer Root Sheath Cells, and Extends the Anagen Phase by Inhibiting 5α-Reductase.

18-ß-Glycyrrhetinic acid, a major component of licorice, stimulated the proliferation of both dermal papilla cells and outer root sheath cells isolated from human hair follicles. Thus, suggesting that this compound promotes hair growth. Furthermore, this compound inhibited the activity of testosterone 5α-reductase, an enzyme responsible for converting androgen to dihydroandrogen, with an IC50 of 137.1 µM. 18-ß-Glycyrrhetinic acid also suppressed the expression of transforming growth factor-ß1 (TGF-ß1), which shifts the hair cycle from the anagen phase to the telogen phase. It suggested that this compound may prolong the anagen phase. Based on these findings, this compound could be a potentially effective treatment for androgenetic alopecia.

Necrosulfonamide promotes hair growth and ameliorates DHT-induced hair growth inhibition.

BACKGROUND: Alopecia affects patients' appearance and psychology. Mixed-lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis plays a role in various skin diseases, but its effect on hair growth is unclear. OBJECTIVE: To investigate the effects of MLKL on hair growth and its regulatory mechanisms and to determine the potential clinical value of Necrosulfonamide (NSA, a MLKL-targeting inhibitor) in promoting hair growth and counteracting dihydrotestosterone (DHT) inhibition of hair growth. METHODS: The expression level of MLKL was detected in the scalp of androgenetic alopecia (AGA) patients and the skin tissues of mice. Knock down MLKL expression or use NSA to observe hair growth in vivo and in vitro. RESULTS: In AGA patients, MLKL expression is elevated in the alopecia areas. In mice, MLKL is significantly expressed in the outer root sheath (ORS) cells of hair follicles, peaking during the catagen phase. Knockdown expression of MLKL in mice skin promoted hair growth. NSA enhanced hair growth and prevented hair follicle regression via the Wnt signaling. Reduced MLKL boosts ORS cell proliferation without directly impacting DPCs' growth. Interestingly, NSA boosts DPCs' proliferation and induction when co-cultured with ORS cells. Besides, NSA alleviated the inhibition of DHT on hair growth in vivo and vitro. CONCLUSION: NSA inhibited the activation of MLKL in ORS cells, promoted the activation of Wnt signal in DPC cells, and improved the inhibition of hair growth by DHT, illuminating a new alopecia mechanism and aiding anti-alopecia drug development.

A Novel 3D Printed Model of Infected Human Hair Follicles to Demonstrate Targeted Delivery of Nanoantibiotics.

Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle's microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment's critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.

Effects of Biomaterials Derived from Germinated Hemp Seeds on Stressed Hair Stem Cells and Immune Cells.

Androgenetic alopecia is a genetic disorder that commonly causes progressive hair loss in men, leading to diminished self-esteem. Although cannabinoids extracted from Cannabis sativa are used in hair loss treatments, no study has evaluated the effects of germinated hemp seed extract (GHSE) and exosomes derived from the calli of germinated hemp seeds on alopecia. Therefore, this study aimed to demonstrate their preventive effects against alopecia using various methodologies, including quantitative PCR, flow cytometry, ELISA, and immunocytochemistry. Our research highlights the preventive functions of GHSE (GE2000: 2000 µg/mL) and exosomes from the calli of germinated hemp seeds (E40: 40 µg/mL) in three biochemical categories: genetic modulation in hair follicle dermal papilla stem cells (HFDPSCs), cellular differentiation, and immune system modulation. Upon exposure to dihydrotestosterone (DT), both biomaterials upregulated genes preventing alopecia (Wnt, ß-catenin, and TCF) in HFDPSCs and suppressed genes activating alopecia (STAT1, 5α-reductase type 1, IL-15R). Additionally, they suppressed alopecia-related genes (NKG2DL, IL2-Rß, JAK1, STAT1) in CD8+ T cells. Notably, E40 exhibited more pronounced effects compared to GE2000. Consequently, both E40 and GE2000 effectively mitigated DT-induced stress, activating mechanisms promoting hair formation. Given the limited research on alopecia using these materials, their pharmaceutical development promises significant economic and health benefits.

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Sophoricoside, a genistein glycoside from Fructus Sophorae, promotes hair growth via activation of M4 muscarinic AChR in dermal papilla cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alopecia, or hair loss, refers to ongoing decline of mature hair on the scalp or any other region of the body. Fructus Sophorae, a fruit from Sophora japonica L., contains various phytochemicals, e.g., sophoricoside, that exhibit a broad range of pharmacological effects. The potential functions of herbal extracts deriving from Fructus Sophorae and/or its major phytochemical, sophoricoside, in treating alopecia are probed here. AIM OF STUDY: The objective was to determine the ability of Fructus Sophorae extract and sophoricoside in promoting hair growth and it signalling mechanism. METHODS: Molecular docking studies were conducted to measure the binding affinities between sophoricoside and M4 mAChR in the allosteric binding site. The mechanism of Fructus Sophorae and sophoricoside in activating the signalling involving Wnt/ß-catenin and muscarinic AChR was evaluated by using immortalized human dermal papilla cell line (DPC), as well as their roles in promoting hair growth. The activity of pTOPflash-luciferase in transfected DPCs was used to examine the transcriptional regulation of Wnt/ß-catenin-mediated genes. RT-PCR was applied to quantify mRNA expressions of the biomarkers in DPCs responsible for hair growth. The phosphorylated protein levels of Wnt/ß-catenin and PI3K/AKT in DPC were revealed by using Western blot analysis. The culture of ex vivo mouse vibrissae hair follicle was used to evaluate the hair growth after the treatments. RESULTS: The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/ß-catenin signalling. The result of molecular docking showed a high binding affinity between sophoricoside and M4 mAChR. The effect of sophoricoside was blocked by specific inhibitor of M4 mAChR, but not by other inhibitors of mAChRs. Sophoricoside promoted hair growth in cultured ex vivo mouse vibrissae hair follicle by acting through M4 mAChR. CONCLUSION: The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/ß-catenin signalling via activation of M4 mAChR. The results suggested beneficial functions of Fructus Sophorae and sophoricoside as a potential candidate in treating alopecia.

Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.

Hair Thickness Growth Effect of Adenosine Complex in Male-/Female-Patterned Hair Loss via Inhibition of Androgen Receptor Signaling.

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.

Combination of Autophagy and Stem Cell Enhancing Properties of Natural Product Extracts in Human Dermal Papilla Stem Cells.

BACKGROUND/AIM: Dermal papilla (DP) stem cells are known for their remarkable regenerative capacity, making them a valuable model for assessing the effects of natural products on cellular processes, including stemness, and autophagy. MATERIALS AND METHODS: Autophagy and stemness characteristics were assessed using real-time RT-PCR to analyze mRNA levels, along with immunofluorescence and western blot techniques for protein level evaluation. RESULTS: Butterfly Pea, Emblica Fruits, Kaffir Lime, and Thunbergia Laurifolia extracts induced autophagy in DP cells. Kaffir Lime-treated cells exhibited increase in the OCT4, NANOG, and SOX2 mRNA (6-, 5, and 5.5-fold, respectively), and protein levels (4-, 3-, and 1.5-fold, respectively). All extracts activated the survival protein kinase B (Akt) in DP cells. CONCLUSION: Natural products are a promising source for promoting hair growth by rejuvenating hair stem cells.

Nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of tofacitinib for treating alopecia areata.

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.

1,25-(OH)2D3 promotes hair growth by inhibiting NLRP3/IL-1ß and HIF-1α/IL-1ß signaling pathways.

Vitamin D is a crucial vitamin that participates in various biological processes through the Vitamin D Receptor (VDR). While there are studies suggesting that VDR might regulate hair growth through ligand-independent mechanisms, the efficacy of Vitamin D in treating hair loss disorders has also been reported. Here, through in vivo experiments in mice, in vitro organ culture of hair follicles, and cellular-level investigations, we demonstrate that 1,25-(OH)2D3 promotes mouse hair regeneration, prolongs the hair follicle anagen, and enhances the proliferation and migration capabilities of dermal papilla cells and outer root sheath keratinocytes in a VDR-dependent manner. Transcriptome analysis of VDR-knockout mouse skin reveals the involvement of HIF-1α, NLRP3, and IL-1ß in these processes. Finally, we confirm that 1,25-(OH)2D3 can counteract the inhibitory effects of DHT on hair growth. These findings suggest that 1,25-(OH)2D3 has a positive impact on hair growth and may serve as a potential therapeutic agent for androgenetic alopecia (AGA).