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Keywords = alopecia

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15 pages, 3724 KiB  
Article
Exploring the Association Between Multidimensional Dietary Patterns and Non-Scarring Hair Loss Using Mendelian Randomization
by Lingfeng Pan, Philipp Moog, Caihong Li, Leonard Steinbacher, Samuel Knoedler, Haydar Kükrek, Ulf Dornseifer, Hans-Günther Machens and Jun Jiang
Nutrients 2025, 17(15), 2569; https://doi.org/10.3390/nu17152569 - 7 Aug 2025
Abstract
Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary [...] Read more.
Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary exposures and hair loss, leveraging genetic variants to address confounding biases. Methods: Genome-wide association study (GWAS) data from 161,625 UK Biobank participants were analyzed, focusing on food preferences and intake patterns. Genetic instruments for each of the 187 dietary exposures were selected at a genome-wide significance threshold (p < 5 × 10−8), with rigorous sensitivity analyses (MR-Egger, MR-PRESSO) to validate causality. Outcomes included AA and AGA datasets from the FinnGen consortium. Results: MR analysis identified 18 specific dietary exposures significantly associated with non-scarring hair loss (FDR < 0.05). Protective effects emerged for antioxidant-rich dietary exposures, represented by higher preferences for melon, onions, and tea. Elevated risks were observed for certain exposures, including croissants, goat cheese, and whole milk. Alcohol consumption exhibited the strongest risk associations. Our extensive analysis of alcohol intake, combining data from multiple studies, consistently identified it as a significant risk factor for both alopecia areata and androgenetic alopecia. Conclusions: These findings imply modifiable dietary patterns in hair loss pathophysiology. A dual strategy is proposed: prioritizing polyphenol-rich plant foods while minimizing pro-inflammatory triggers like processed carbohydrates and alcohol. Clinically, tailored dietary adjustments—reducing ultra-processed foods and alcohol—may complement existing therapies for hair loss management. Full article
(This article belongs to the Section Nutrition and Metabolism)
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37 pages, 22351 KiB  
Article
The Extract of Periplaneta americana (L.) Promotes Hair Regrowth in Mice with Alopecia by Regulating the FOXO/PI3K/AKT Signaling Pathway and Skin Microbiota
by Tangfei Guan, Xin Yang, Canhui Hong, Zehao Zhang, Peiyun Xiao, Yongshou Yang, Chenggui Zhang and Zhengchun He
Curr. Issues Mol. Biol. 2025, 47(8), 619; https://doi.org/10.3390/cimb47080619 - 4 Aug 2025
Viewed by 76
Abstract
Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for [...] Read more.
Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for alopecia. This study aimed to systematically investigate the efficacy and mechanisms of PA extracts in promoting hair regeneration. A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of a Periplaneta americana extract was validated by evaluating hair regrowth status and skin pathological staining in C57BL/6J mice. Transcriptomics, metabolomics, RT-qPCR, and 16s rRNA techniques were integrated to dissect the underlying mechanisms of its hair-growth-promoting effects. PA-011 significantly promoted hair regeneration in depilated mice via multiple mechanisms: enhanced skin superoxide dismutase activity and upregulated vascular endothelial growth factor expression; modulated FOXO/PI3K/AKT signaling pathway and restored skin microbiota homeostasis; and accelerated transition of hair follicles from the telogen to anagen phase. PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and the skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation. Full article
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33 pages, 8604 KiB  
Article
Sulforaphane-Rich Broccoli Sprout Extract Promotes Hair Regrowth in an Androgenetic Alopecia Mouse Model via Enhanced Dihydrotestosterone Metabolism
by Laxman Subedi, Duc Dat Le, Eunbin Kim, Susmita Phuyal, Arjun Dhwoj Bamjan, Vinhquang Truong, Nam Ah Kim, Jung-Hyun Shim, Jong Bae Seo, Suk-Jung Oh, Mina Lee and Jin Woo Park
Int. J. Mol. Sci. 2025, 26(15), 7467; https://doi.org/10.3390/ijms26157467 - 1 Aug 2025
Viewed by 382
Abstract
Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on [...] Read more.
Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article
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23 pages, 3128 KiB  
Review
Advances in Transdermal Delivery Systems for Treating Androgenetic Alopecia
by Shilong Xu, Lian Zhou, Haodong Zhao and Siwen Li
Pharmaceutics 2025, 17(8), 984; https://doi.org/10.3390/pharmaceutics17080984 - 30 Jul 2025
Viewed by 522
Abstract
Androgenetic alopecia (AGA) is the most prevalent form of alopecia areata. Traditional treatment options, including minoxidil, finasteride, and hair transplantation, have their limitations, such as skin irritation, systemic side effects, invasiveness, and high costs. The transdermal drug delivery system (TDDS) offers an innovative [...] Read more.
Androgenetic alopecia (AGA) is the most prevalent form of alopecia areata. Traditional treatment options, including minoxidil, finasteride, and hair transplantation, have their limitations, such as skin irritation, systemic side effects, invasiveness, and high costs. The transdermal drug delivery system (TDDS) offers an innovative approach for treating AGA by administering medications through the skin to achieve localized and efficient delivery while overcoming the skin barrier. This review systematically explores the application of TDDS in AGA treatment, highlighting emerging technologies such as microneedles (MNs), liposomes, ionic liquids (ILs), nanostructured lipid carriers (NLCs), and transporters (TFs). It analyzes the underlying mechanisms that enhance drug penetration through hair follicles. Finally, this review presents a forward-looking perspective on the future use of TDDS in the management of AGA, aiming to provide insights and references for designing effective transdermal drug delivery systems for this condition. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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15 pages, 1507 KiB  
Systematic Review
Adenosine as an Active Ingredient in Topical Preparations Against Hair Loss: A Systematic Review and Meta-Analysis of Published Clinical Trials
by Ewelina Szendzielorz and Radoslaw Spiewak
Biomolecules 2025, 15(8), 1093; https://doi.org/10.3390/biom15081093 - 28 Jul 2025
Viewed by 803
Abstract
Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA [...] Read more.
Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA and PICO guidelines and included articles indexed in PubMed, Scopus, and Web of Science. The strength of evidence was assessed according to the GRADE system. Wherever feasible, data were extracted for a meta-analysis. Among 8625 articles returned by the query, 7 clinical trials were identified of topical adenosine (lotion, shampoo) in hair loss. They unanimously reported on a reduction in hair loss and increase in hair density (strength of evidence very low to moderate). A meta-analysis of three eligible trials showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21) and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion. The results from clinical trials published until now suggest that topical adenosine increases hair thickness, reduces excessive hair loss, stimulates hair regrowth, and increases hair density. The overall strength of evidence remains low due to flawed design and small sample sizes in most trials. Nevertheless, topical adenosine products seem worth trying, especially in the case of contraindications or adverse effects to approved medicinal products for hair loss. Further, better designed trials of adenosine in hair loss are warranted. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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22 pages, 844 KiB  
Article
Anti-Hair Loss Potential of Perilla Seed Extracts: In Vitro Molecular Insights from Supercritical Fluid Extraction
by Anurak Muangsanguan, Warintorn Ruksiriwanich, Pipat Tangjaidee, Korawan Sringarm, Chaiwat Arjin, Pornchai Rachtanapun, Sarana Rose Sommano, Korawit Chaisu, Apinya Satsook and Juan Manuel Castagnini
Foods 2025, 14(15), 2583; https://doi.org/10.3390/foods14152583 - 23 Jul 2025
Viewed by 441
Abstract
Perilla seed has long been recognized in traditional diets for its health-promoting properties, but its potential role in hair loss prevention remains underexplored. This study compared three extraction methods—maceration (MAC), screw pressing (SC), and supercritical fluid extraction (SFE)—to determine their efficiency in recovering [...] Read more.
Perilla seed has long been recognized in traditional diets for its health-promoting properties, but its potential role in hair loss prevention remains underexplored. This study compared three extraction methods—maceration (MAC), screw pressing (SC), and supercritical fluid extraction (SFE)—to determine their efficiency in recovering bioactive compounds and their effects on androgenetic alopecia (AGA)-related pathways. The SFE extract contained the highest levels of polyunsaturated fatty acids and tocopherols, while MAC uniquely recovered a broader range of polyphenols. Among all extracts, SFE-derived perilla seed extract showed the most consistent biological effects, promoting proliferation of human hair follicle dermal papilla cells (HFDPCs) by 139.4 ± 1.1% at 72 h (p < 0.05). It also reduced TBARS and nitrite levels in HFDPCs to 66.75 ± 0.62% of control and 0.87 ± 0.01 μM, respectively, indicating strong antioxidant and anti-inflammatory effects. Importantly, the SFE extract significantly downregulated SRD5A1-3 and TGF-β1 expression—key genes involved in androgen-mediated hair follicle regression—outperforming finasteride, dutasteride, and minoxidil in vitro by approximately 1.10-fold, 1.25-fold, and 1.50-fold, respectively (p < 0.05). These findings suggest that perilla seed extract obtained via supercritical fluid extraction may offer potential as a natural candidate to prevent hair loss through multiple biological mechanisms. These in vitro results support its further investigation for potential application in functional food or nutraceutical development targeting scalp and hair health. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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18 pages, 8559 KiB  
Article
Recombinant Type XVII Collagen Promotes Hair Growth by Activating the Wnt/β-Catenin and SHH/GLI Signaling Pathways
by Yuyao Zhang, Shiyu Yin, Ru Xu, Jiayu Xiao, Rui Yi, Jiahui Mao, Zhiguang Duan and Daidi Fan
Cosmetics 2025, 12(4), 156; https://doi.org/10.3390/cosmetics12040156 - 23 Jul 2025
Viewed by 723
Abstract
(1) Background: As society progresses, increasing numbers of individuals are experiencing hair loss, which can be attributed to factors such as unhealthy diets, insufficient sleep, stress, and hormonal imbalances. Currently available pharmacological treatments for hair loss often cause undesirable side effects, highlighting the [...] Read more.
(1) Background: As society progresses, increasing numbers of individuals are experiencing hair loss, which can be attributed to factors such as unhealthy diets, insufficient sleep, stress, and hormonal imbalances. Currently available pharmacological treatments for hair loss often cause undesirable side effects, highlighting the urgent need to explore safer and more effective agents to promote hair restoration. This study investigated the role of recombinant human type XVII collagen derived from the α1 chain (rhCOL17A1) in facilitating hair growth and restoration. (2) Methods: We analyzed the impact of rhCOL17A1 on the mRNA expression of several growth factors, as well as Bcl-2 and Bax, at the cellular level. Moreover, the effects of rhCOL17A1 on the expression of key proteins in the Wnt/β-catenin and Sonic Hedgehog (SHH)/GLI signaling pathways were examined by Western blotting (WB). At the organismal level, we established a model in C57BL/6 mice through chronic subcutaneous administration of 5% testosterone propionate. We subsequently assessed the effect of rhCOL17A1 on hair regrowth via histological analysis using hematoxylin and eosin (H&E) staining and immunofluorescence staining. (3) Results: rhCOL17A1 contributes to the resistance of hair follicle dermal papilla cells (HFDPCs) to apoptosis. rhCOL17A1 activates the Wnt/β-catenin and SHH/GLI signaling pathways, and increases the expression of type XVII collagen (COLXVII), thereby creating a favorable environment for hair growth. Furthermore, rhCOL17A1 exerts a significant growth-promoting effect at the animal level. (4) Conclusions: rhCOL17 promotes hair growth by activating the Wnt/β-catenin and SHH/GLI signaling pathways and upregulating COLXVII expression. Full article
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35 pages, 8014 KiB  
Article
Chitosan Nanoparticles for Topical Drug Delivery in Chemotherapy-Induced Alopecia: A Comparative Study of Five Repurposed Pharmacological Agents
by Salma A. Fereig, John Youshia, Ghada M. El-Zaafarany, Mona G. Arafa and Mona M. A. Abdel-Mottaleb
Pharmaceuticals 2025, 18(7), 1071; https://doi.org/10.3390/ph18071071 - 21 Jul 2025
Viewed by 571
Abstract
Background/Objectives: Chemotherapy-induced alopecia is a common and distressing side effect of cancer treatment, significantly impacting patients’ psychological well-being. Nanocarriers offer a promising strategy for targeted drug delivery to hair follicles, while chitosan nanoparticles have demonstrated hair-growth-promoting properties. This study explores the potential [...] Read more.
Background/Objectives: Chemotherapy-induced alopecia is a common and distressing side effect of cancer treatment, significantly impacting patients’ psychological well-being. Nanocarriers offer a promising strategy for targeted drug delivery to hair follicles, while chitosan nanoparticles have demonstrated hair-growth-promoting properties. This study explores the potential of chitosan nanoparticles as a topical delivery system for five pharmacological agents—phenobarbital, pioglitazone, rifampicin, N-acetylcysteine, and tacrolimus—to prevent chemotherapy-induced alopecia. Methods: Drug-loaded chitosan nanoparticles were prepared using the ionic gelation technique and characterized by particle size, zeta potential, entrapment efficiency, FT-IR spectroscopy, and TEM imaging. Their efficacy was assessed in a cyclophosphamide-induced alopecia model in C57BL/6 mice through macroscopic observation, histopathological examination, and scanning electron microscopy of regrown hair. Results: The prepared particles were spherical, cationic, and between 205 and 536 nm in size. The entrapment efficiencies ranged from 8% to 63%. All five drugs mitigated follicular dystrophy, shifting the hair follicle response from dystrophic catagen to dystrophic anagen. Phenobarbital demonstrated the most significant hair regrowth and quality improvements, followed by N-acetyl cysteine and pioglitazone. Tacrolimus showed moderate efficacy, while rifampicin was the least effective. Conclusions: These findings suggest that phenobarbital-loaded chitosan nanoparticles represent a promising approach for the prevention and treatment of chemotherapy-induced alopecia, warranting further investigation for clinical applications. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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10 pages, 219 KiB  
Article
Alopecia Areata Associated with Dupilumab: National Database Study
by Tarun Sontam, Humaira Nfn, Jodi Yanking Li, Sehar Nadeem, Katie Beier, Neil K. Jairath and Vignesh Ramachandran
Diagnostics 2025, 15(14), 1828; https://doi.org/10.3390/diagnostics15141828 - 21 Jul 2025
Viewed by 484
Abstract
Background: Alopecia areata (AA), an autoimmune condition causing non-scarring hair loss, often coexists with atopic dermatitis (AD) due to shared T-helper cell type 2 (Th2)-mediated pathways. Dupilumab, a monoclonal antibody inhibiting IL-4 and IL-13 signaling, is a cornerstone treatment for AD but has [...] Read more.
Background: Alopecia areata (AA), an autoimmune condition causing non-scarring hair loss, often coexists with atopic dermatitis (AD) due to shared T-helper cell type 2 (Th2)-mediated pathways. Dupilumab, a monoclonal antibody inhibiting IL-4 and IL-13 signaling, is a cornerstone treatment for AD but has conflicting reports regarding its impact on AA, with some suggesting therapeutic benefits and others indicating AA induction. Methods: This retrospective study, utilizing the TriNetX Research Network’s de-identified data from over 300 million patient records, investigates the association between dupilumab use and AA risk in AD patients. Results: After propensity score matching, 23,782 dupilumab users were compared with an equal number of controls. Results revealed a statistically significant increased AA risk in dupilumab users (odds ratio: 1.436, 95% CI: 1.066–1.935, p = 0.0167) after 16 weeks. Cases occurring within 16 weeks were excluded. Conclusions: Potential mechanisms include immune rebalancing, with Th2 suppression possibly upregulating Th1/Th17 pathways or unmasking latent AA in predisposed individuals. These findings challenge dupilumab’s potential as an AA treatment and highlight the need for vigilant monitoring, including routine scalp examinations and patient education. Future research should focus on mechanistic pathways, risk stratification, and comparative studies with other biologics to optimize personalized treatment strategies for AD and AA. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, and Management of Hair Disorders)
25 pages, 2029 KiB  
Article
Germination Enhances Phytochemical Profiles of Perilla Seeds and Promotes Hair Growth via 5α-Reductase Inhibition and Growth Factor Pathways
by Anurak Muangsanguan, Warintorn Ruksiriwanich, Pichchapa Linsaenkart, Pipat Tangjaidee, Korawan Sringarm, Chaiwat Arjin, Pornchai Rachtanapun, Sarana Rose Sommano, Korawit Chaisu, Apinya Satsook and Juan Manuel Castagnini
Biology 2025, 14(7), 889; https://doi.org/10.3390/biology14070889 - 20 Jul 2025
Viewed by 509
Abstract
Seed germination is recognized for enhancing the accumulation of bioactive compounds. Perilla frutescens (L.) Britt., commonly known as perilla seed, is rich in fatty acids that may be beneficial for anti-hair loss. This study investigated the hair regeneration potential of perilla seed extracts—non-germinated [...] Read more.
Seed germination is recognized for enhancing the accumulation of bioactive compounds. Perilla frutescens (L.) Britt., commonly known as perilla seed, is rich in fatty acids that may be beneficial for anti-hair loss. This study investigated the hair regeneration potential of perilla seed extracts—non-germinated (NG-PS) and germinated in distilled water (0 ppm selenium; G0-PS), and germinated with 80 ppm selenium (G80-PS)—obtained from supercritical fluid extraction (SFE) and screw compression (SC). SFE extracts exhibited significantly higher levels of polyphenols, tocopherols, and fatty acids compared to SC extracts. Among the germinated groups, G0-PS showed the highest bioactive compound content and antioxidant capacity. Remarkably, treatment with SFE-G0-PS led to a significant increase in the proliferation and migration of hair follicle cells, reaching 147.21 ± 2.11% (p < 0.05), and resulted in complete wound closure. In addition, its antioxidant and anti-inflammatory properties were reflected by a marked scavenging effect on TBARS (59.62 ± 0.66% of control) and suppressed nitrite amounts (0.44 ± 0.01 µM). Moreover, SFE-G0-PS markedly suppressed SRD5A1-3 gene expression—key regulators in androgenetic alopecia—in both DU-145 and HFDPCs, with approximately 2-fold and 1.5-fold greater inhibition compared to finasteride and minoxidil, respectively. Simultaneously, it upregulated the expression of hair growth-related genes, including CTNNB1, SHH, SMO, GLI1, and VEGF, by approximately 1.5-fold, demonstrating stronger activation than minoxidil. These findings suggest the potential of SFE-G0-PS as a natural therapeutic agent for promoting hair growth and preventing hair loss. Full article
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19 pages, 259 KiB  
Article
Dietary and Genetic Aspects of Polycystic Ovary Syndrome (PCOS) in Polish Women—Part II: Association of CYP19, FTO, MC4R and INSR Gene Polymorphisms with Clinical Symptoms of PCOS
by Karolina Nowosad, Małgorzata Ostrowska, Paweł Glibowski, Katarzyna Iłowiecka and Wojciech Koch
Genes 2025, 16(7), 840; https://doi.org/10.3390/genes16070840 - 18 Jul 2025
Viewed by 648
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial disorder influenced by both environmental and genetic factors. The aim of this study was to evaluate associations between selected polymorphisms (CYP19, INSR, FTO, MC4R) and the clinical manifestations of PCOS [...] Read more.
Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial disorder influenced by both environmental and genetic factors. The aim of this study was to evaluate associations between selected polymorphisms (CYP19, INSR, FTO, MC4R) and the clinical manifestations of PCOS in a Polish female population. Methods: A total of 50 women (25 with PCOS and 25 healthy controls) were included. Genetic variants were identified using Polymerase Chain Reaction (PCR)-based methods. The frequencies of genotypes and alleles were compared between groups. Clinical symptoms such as irregular menstruation, hirsutism, acne, androgenetic alopecia, and overweight were assessed in relation to genotype. Results: No significant differences were found in genotype distributions for CYP19, FTO, INSR, or MC4R between PCOS and control groups. The MC4R polymorphisms showed deviations from Hardy–Weinberg equilibrium, possibly reflecting population-specific effects. Conclusions: Although most analyzed variants were not directly associated with PCOS in this cohort, the observed link between INSR rs1799817 and acne suggests a role in androgen-related symptoms. These findings contribute new insights to the genetic background of PCOS in Polish women and support the need for further studies combining genetic and phenotypic data in diverse populations. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
17 pages, 1772 KiB  
Article
Exploration of the Possible Relationships Between Gut and Hypothalamic Inflammation and Allopregnanolone: Preclinical Findings in a Post-Finasteride Rat Model
by Silvia Diviccaro, Roberto Oleari, Federica Amoruso, Fabrizio Fontana, Lucia Cioffi, Gabriela Chrostek, Vera Abenante, Jacopo Troisi, Anna Cariboni, Silvia Giatti and Roberto Cosimo Melcangi
Biomolecules 2025, 15(7), 1044; https://doi.org/10.3390/biom15071044 - 18 Jul 2025
Viewed by 2028
Abstract
Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid [...] Read more.
Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid homeostasis, neuroactive steroid deficiency (notably allopregnanolone, ALLO), and gut–brain axis alterations. Objective: This study aimed to investigate the effects of finasteride withdrawal (FW) in a rat model and evaluate the potential protective effects of ALLO on gut and hypothalamic inflammation. Methods: Adult male Sprague Dawley rats were treated with finasteride for 20 days, followed by one month of drug withdrawal. A subgroup received ALLO treatment during the withdrawal. Histological, molecular, and biochemical analyses were performed on the colon and hypothalamus. Gut microbiota-derived metabolites and markers of neuroinflammation and blood–brain barrier (BBB) integrity were also assessed. Results: At FW, rats exhibited significant colonic inflammation, including a 4.3-fold increase in Mφ1 levels (p < 0.001), a 2.31-fold decrease in butyrate concentration (p < 0.01), and elevated hypothalamic GFAP and Iba-1 protein expression (+360%, p < 0.01 and +100%, p < 0.01, respectively). ALLO treatment rescued these parameters in both the colon and hypothalamus but only partially restored mucosal and BBB structural integrity, as well as the NF-κB/PPARγ pathway. Conclusions: This preclinical study shows that FW causes inflammation in both the gut and hypothalamus in rats. ALLO treatment helped reduce several of these effects. These results suggest ALLO could have a protective role and have potential as a treatment for PFS patients. Full article
(This article belongs to the Section Molecular Medicine)
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21 pages, 7139 KiB  
Article
Comparative Study of a Topical and Oral Combination Therapy Containing Oleanolic Acid, Apigenin, and Biotinyl Tripeptide-1 in Patients with Androgenetic Alopecia: A Prospective, Open-Label Trial
by Vlad-Mihai Voiculescu and Mihai Lupu
Cosmetics 2025, 12(4), 152; https://doi.org/10.3390/cosmetics12040152 - 16 Jul 2025
Viewed by 1012
Abstract
Background: Androgenetic alopecia (AGA) is a prevalent condition characterized by progressive follicular miniaturization. Minoxidil topical treatment and finasteride oral treatment are the golden standard, but they are limited by local and systemic adverse effects. Combination therapies targeting both follicular stimulation and nutritional support [...] Read more.
Background: Androgenetic alopecia (AGA) is a prevalent condition characterized by progressive follicular miniaturization. Minoxidil topical treatment and finasteride oral treatment are the golden standard, but they are limited by local and systemic adverse effects. Combination therapies targeting both follicular stimulation and nutritional support may enhance clinical outcomes. Objective: To evaluate the efficacy of a combined topical and oral therapy compared to topical monotherapy in patients with AGA using trichoscopic and clinical parameters. Methods: In this open-label, prospective trial, 48 patients were assigned to receive either a topical spray alone (Group A) or in combination with oral capsules (Group B) for 3 months. Trichoscopic parameters were assessed at baseline and post-treatment. Paired and independent t-tests, along with Cohen’s d effect sizes, were used to evaluate intra- and inter-group changes. Results: Both groups demonstrated improvements in hair density, thickness, and anagen/telogen ratio. Group B exhibited significantly greater increases in total hair count and anagen conversion (p < 0.05). The effect sizes ranged from small to large, with the most pronounced changes observed in anagen/telogen ratio (Cohen’s d = 0.841) in males. Conclusions: The combination of topical and oral treatment led to greater trichologic improvements than topical therapy alone. While extrapolated projections at 6 and 12 months suggest continued benefit, future studies with longer duration and placebo controls are required to validate these findings. Full article
(This article belongs to the Section Cosmetic Formulations)
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18 pages, 5892 KiB  
Article
CXCL12 Drives Reversible Fibroimmune Remodeling in Androgenetic Alopecia Revealed by Single-Cell RNA Sequencing
by Seungchan An, Mei Zheng, In Guk Park, Leegu Song, Jino Kim, Minsoo Noh and Jong-Hyuk Sung
Int. J. Mol. Sci. 2025, 26(14), 6568; https://doi.org/10.3390/ijms26146568 - 8 Jul 2025
Viewed by 643
Abstract
Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) [...] Read more.
Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) have been suggested as androgen-responsive stromal cells and a potential source of CXCL12, a chemokine implicated in fibroimmune pathology, but their precise role in AGA has not been fully established. In this study, we performed single-cell transcriptomic profiling of a testosterone-induced mouse model of AGA, with or without treatment of CXCL12-neutralizing antibody, to elucidate the pathological role of CXCL12 in mediating stromal-immune interactions. Our analysis suggested that DFs are the primary androgen-responsive population driving CXCL12 expression. Autocrine CXCL12-ACKR3 signaling in DFs activated TGF-β pathways and promoted fibrotic extracellular matrix deposition. In parallel, paracrine CXCL12-CXCR4 signaling reprogrammed Sox2+Twist1+ dermal papilla cells (DPCs) and promoted the accumulation of pro-fibrotic Trem2+ macrophages, contributing to impaired hair follicle regeneration. Notably, CXCL12 blockade attenuated these stromal and immune alterations, restored the regenerative capacity of DPCs, reduced pro-fibrotic macrophage infiltration, and promoted hair regrowth. Together, these findings identify CXCL12 as a central mediator of androgen-induced fibroimmune remodeling and highlight its potential as a therapeutic target in AGA. Full article
(This article belongs to the Section Molecular Biology)
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43 pages, 25464 KiB  
Article
Exploring the Efficacy and Potential Mechanisms of Topical Periplaneta americana (L.) Extract in Treating Androgenetic Alopecia in a Mouse Model: A Systems Pharmacology and Skin Microbiome Analysis
by Tangfei Guan, Xin Yang, Canhui Hong, Peiyun Xiao, Yongshou Yang, Chenggui Zhang and Zhengchun He
Biology 2025, 14(7), 831; https://doi.org/10.3390/biology14070831 - 8 Jul 2025
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Abstract
Androgenetic alopecia (AGA), the most prevalent form of hair loss worldwide, faces significant therapeutic challenges due to high costs and limited efficacy of current interventions, necessitating safer and more effective solutions. Periplaneta americana (L.)-derived PA-011, endowed with anti-inflammatory and antioxidant properties, has demonstrated [...] Read more.
Androgenetic alopecia (AGA), the most prevalent form of hair loss worldwide, faces significant therapeutic challenges due to high costs and limited efficacy of current interventions, necessitating safer and more effective solutions. Periplaneta americana (L.)-derived PA-011, endowed with anti-inflammatory and antioxidant properties, has demonstrated notable hair growth-promoting effects in AGA mouse models. This study employed LC-MS/MS, peptidomics, and network pharmacology to characterize PA-011’s chemical composition and predict its potential targets in AGA pathogenesis. Using Western blot and RT-qPCR, PA-011 intervention significantly inhibited inflammatory responses and oxidative stress levels in mouse skin tissues. Concurrently, PA-011 activated the proliferative potential of hair follicle stem cells, as demonstrated by upregulated expression of the cell proliferation marker Ki67, and activated the Wnt/β-catenin signaling pathway in DHT-induced AGA mice. Transcriptomic and metabolomic analyses revealed multi-target effects of PA-011, including modulation of PI3K-Akt/MAPK pathways, pentose phosphate metabolism, and amino acid biosynthesis. 16S rRNA sequencing and metagenomic analysis showed that AGA disrupts skin microbial homeostasis, while PA-011 intervention normalized the microbiota composition. Topical application of PA-011 promoted robust hair regrowth without detectable toxicity in safety assessments. This preclinical study establishes PA-011 as a promising candidate for AGA therapy, warranting further translational investigation. Full article
(This article belongs to the Section Medical Biology)
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