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Bi L, Kan H, Wang J, Ding Y, Huang Y, Wang C, Du Y, Lu C, Zhao M, Sun W, Su T, Fan W. Whether the transient hair shedding phase exist after minoxidil treatment and does it predict treatment efficacy? A retrospective study in androgenetic alopecia patients. J DERMATOL TREAT 2025; 36:2480739. [PMID: 40122142 DOI: 10.1080/09546634.2025.2480739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 03/04/2025] [Indexed: 03/25/2025]
Abstract
PURPOSE Minoxidil is a routinely used drug in treating multiple hair disorders. This study aimed to investigate the facticity of the temporal increase in the hair shedding amount after topical use of minoxidil. MATERIALS AND METHODS We selected 49 patients who used 2% or 5% minoxidil topically to treat androgenetic alopecia for 24 weeks. The amount of hair shedding was recorded every four weeks before and after the treatment. The BASP classification and trichoscopy test results were also recorded before and after the treatment. The relative amount of hair shedding (RAHS) was defined as the recorded number of hair shedding after normalization. The correlation between the maximum RAHS (MRAHS) and the sulfotransferase activity as well as the therapeutic effect was calculated. RESULTS A temporary increase in the amount of hair shedding was detected in the first 12 weeks. This increase has a longer duration in patients treated with 2% minoxidil compared to 5%. Its severity was correlated with the improvement of trichoscopy tests only in patients with 5% minoxidil but not in 2%. However, both patients in the 2% and 5% minoxidil groups had a significant association between the MRAHS and the improvement in BASP classification. CONCLUSION The amount of hair shedding increases temporarily after the topical minoxidil use, the level of which is a potential treatment efficacy.
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Affiliation(s)
- Lingbo Bi
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Dermatology, China-Japan Friendship Hospital, Beijing, China
| | - Haili Kan
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Wang
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yunbu Ding
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuanbo Huang
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Dermatology and Venereology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Chaofan Wang
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yimei Du
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Changpei Lu
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Zhao
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weiling Sun
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tong Su
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Dermatology, Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Weixin Fan
- Department of Dermatology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Xie J, Yang Q, Zhang Y, Zheng K, Geng H, Wu Y. The Bioengineering of Microspheric Skin Organoids and Their Application in Drug Screening. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2416863. [PMID: 40344618 PMCID: PMC12165074 DOI: 10.1002/advs.202416863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 04/17/2025] [Indexed: 05/11/2025]
Abstract
It has been a challenge to develop skin models which exhibit the key characteristics of the human skin and facilitate high-throughput drug screening. In this study, a method is developed to construct microspheric skin organoids based on spinning bioreactors. The organoid consists of a core-shell structure to mimic the bilayered skin structure, where the shell is composed of cultured human keratinocytes, resembling the epidermis, and the core, which mimics the dermis, comprises human dermal fibroblasts and collagen. In fabrication of the organoid, the cores are cultured with keratinocytes in spinner flasks under defined conditions to facilitate epidermal growth and differentiation to form mature barrier. To enable efficient drug screening, the organoid is equipped with a luciferase reporter to detect canonical Wnt activation, and Minoxidil is identified to induce epidermal Wnt/beta-catenin pathway signaling. Thus, the study has developed a novel method for efficient preparation of uniform microspheric skin organoids with potential applications for high-throughput drug testing and screening.
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Affiliation(s)
- Jundong Xie
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
| | - Qingyang Yang
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
- Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education InstitutesTsinghua Shenzhen International Graduate SchoolTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
| | - Yanan Zhang
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
| | - Ke Zheng
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
- Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education InstitutesTsinghua Shenzhen International Graduate SchoolTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
| | - Hongya Geng
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
- Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education InstitutesTsinghua Shenzhen International Graduate SchoolTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
| | - Yaojiong Wu
- State Key Laboratory of Chemical Oncogenomicsand Institute of Biopharmaceutical and Health Engineering (iBHE)Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
- Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education InstitutesTsinghua Shenzhen International Graduate SchoolTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China
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Li Y, Mu Y, Chen X, Zhao Y, Ji C, Xu R, Jiang R, Liu F, Wang M, Sun L. Deoxyshikonin from Arnebiae Radix promotes hair growth by targeting the Wnt/β-catenin signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 140:156590. [PMID: 40049105 DOI: 10.1016/j.phymed.2025.156590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/27/2025] [Accepted: 02/26/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Alopecia is a common skin condition with limited effective treatments. Arnebiae Radix (AR) is a traditional Asian herb used for various skin disorders. However, its specific components and the mechanisms underlying its hair growth-promoting effects remain elusive. Therefore, this study aimed to investigate the primary active components in AR that are responsible for hair growth as well as determine the molecular mechanisms responsible for treating alopecia. METHODS Alopecia areata mice were employed to assess the influence of AR extracts on hair growth. The active AR components were identified via High-Performance Liquid Chromatography (HPLC). Furthermore, network pharmacology and molecular docking were carried out to predict the key targets of the main active AR compound, which were validated by Surface Plasma Resonance (SPR) analysis. Moreover, the mechanism of action of the identified active AR compound on human dermal papilla cells (HDPCs) and alopecia areata mice was investigated to determine its effects on relevant signaling pathways. RESULTS It was found that Deoxyshikonin (Ds) was the active component in AR with hair growth-promoting potential. Furthermore, it was predicted that Ds targeted 112 alopecia-related targets, including biological processes (such as positive modulation of cell migration and protein phosphorylation) and pathways (including cell cycle- and Wnt signaling pathway-related genes pathways). Network analysis revealed that CCND1 and GSK3β were the hub targets of Ds when treating alopecia. Molecular docking showed a strong binding affinity between Ds and GSK3β, which was validated by SPR results. Moreover, Ds improved HDPC's proliferation ability and promoted hair regeneration in alopecia mice. Similarly, Ds increased VEGF and IGF-1, reduced TGF-β1 content and GSK3β expression, and enhanced the p-GSK3β and β-catenin expression in the Wnt/β-catenin pathway. CONCLUSION This study showed that Ds was the main active AR component with promising potential as a hair growth stimulant. Mechanistically, Ds primarily targets GSK3β to promote the Wnt/β-catenin signaling pathway. This suggests that Ds could be an innovative therapeutic candidate for promoting hair regeneration.
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Affiliation(s)
- Yingna Li
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Yanhong Mu
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Xinyue Chen
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Yiming Zhao
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Chunlei Ji
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Rong Xu
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Rui Jiang
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Changchun University of Chinese Education Medicine, Changchun, Jilin 130117, China
| | - Fangbing Liu
- Northeast Asian Institute of Traditional Chinese Medicine, Changchun University Chinese of Medicine, Changchun, 130117, China
| | - Manying Wang
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
| | - Liwei Sun
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Changchun University of Chinese Education Medicine, Changchun, Jilin 130117, China.
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Kim J, Song SY, Sung JH. Recent Advances in Drug Development for Hair Loss. Int J Mol Sci 2025; 26:3461. [PMID: 40331976 PMCID: PMC12026576 DOI: 10.3390/ijms26083461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/29/2025] [Accepted: 04/03/2025] [Indexed: 05/08/2025] Open
Abstract
Hair loss disorders pose a substantial global health burden, affecting millions of individuals and significantly impacting quality of life. Despite the widespread use of approved therapeutics like minoxidil and finasteride, their clinical efficacy remains limited. These challenges underscore the pressing need for more targeted and effective therapeutic solutions. This review examines the latest innovations in hair loss drug discovery, with a focus on small-molecule inhibitors, biologics, and stem cell-based therapies. By integrating insights from molecular mechanisms and leveraging advancements in research methods, the development of next-generation therapeutics holds the potential to transform the clinical management of hair loss disorders. Future drug development for hair loss disorders should prioritize antibody therapy and cell-based treatments, as these approaches offer unprecedented opportunities to address the limitations of existing options. Antibody therapies enable precise targeting of key molecular pathways involved in hair follicle regulation, providing highly specific and effective interventions. Similarly, cell-based therapies, including stem cell transplantation and dermal papilla cell regeneration, directly address the regenerative capacity of hair follicles, offering transformative potential for hair restoration.
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Affiliation(s)
- Jino Kim
- New Hair Institute, Seoul 06034, Republic of Korea;
| | - Seung-Yong Song
- Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul 06134, Republic of Korea;
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Andrade JFM, Verbinnen A, Bakst A, Cunha-Filho M, Gelfuso GM, Gratieri T. Topical dutasteride for androgenic alopecia: current state and prospects. Ther Deliv 2025; 16:271-283. [PMID: 39641480 PMCID: PMC11875473 DOI: 10.1080/20415990.2024.2437973] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 12/02/2024] [Indexed: 12/07/2024] Open
Abstract
Androgenic alopecia has a high incidence, affecting 80% of men and 50% of women in their lifetimes. Although not a life-threatening disease, it can be a deep psychological burden to patients and still lacks an effective and safe treatment. Dutasteride is a5-alpha-reductase inhibitor approved to treat benign prostatic hyperplasia that is also commonly prescribed off-label to treat androgenic alopecia. However, oral dutasteride may cause several severe sexual and neurological sideeffects. Therefore, an effective, localized dutasteride treatment that can reduce the effects of systemic uptake is of great interest. Here, we review available therapies to treat androgenic alopecia focusing on topicalformulations developed thus far-including minoxidil, finasteride, and cosmetics-and on dutasteride-loaded nanocarriers targeting hair follicles.
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Affiliation(s)
| | | | | | - Marcílio Cunha-Filho
- Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia (UnB), Brasília, Brazil
| | - Guilherme M. Gelfuso
- Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia (UnB), Brasília, Brazil
| | - Taís Gratieri
- Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia (UnB), Brasília, Brazil
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Kang JI, Choi YK, Han SC, Hyun JW, Koh YS, Oh J, Boo HJ, Yoo ES, Kang HK. 5-Fluorouracil induces hair loss by inhibiting β-catenin signaling and angiogenesis. Chem Biol Interact 2025; 408:111416. [PMID: 39922517 DOI: 10.1016/j.cbi.2025.111416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/24/2025] [Accepted: 02/05/2025] [Indexed: 02/10/2025]
Abstract
Chemotherapy-induced alopecia (CIA) is a side effect of the anticancer drug 5-fluorouracil (5-FU). However, the mechanism of action in hair follicle cells is unclear. This study investigated the mechanism of action of 5-FU on the hair cycle and growth in vitro and in vivo. Intraperitoneal injection of 5-FU into C57BL/6 mice delayed anagen initiation, resulting in small hair follicles. 5-FU inhibited angiogenesis by reducing cluster of differentiation 31+ cells, vascular endothelial growth factor, and fetal liver kinase-1 expression in mouse skin tissue and rat vibrissa dermal papilla (rDP) cells. 5-FU induced cell death in rDP cells and keratinocytes by enhancing cell cycle arrest or reducing the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2-associated X levels. Immunoblotting and confocal microscopy showed that 5-FU inhibited the nuclear translocation of β-catenin in rDP cells and decreased fibroblast growth factor 7 and 10 secretion. Conversely, molecule-specific inhibitors did not prevent rDP cell death despite protein kinase B and Jun N-terminal kinase activation by 5-FU, indicating their indirect involvement. These results suggest that 5-FU inhibits wingless-related integration site/β-catenin signaling and angiogenesis, resulting in anagen-to-catagen transition and delaying anagen initiation. This study provides foundational data for developing treatments against CIA in patients with cancer undergoing 5-FU chemotherapy.
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Affiliation(s)
- Jung-Il Kang
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Youn Kyung Choi
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Sang-Chul Han
- Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Jin Won Hyun
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Young-Sang Koh
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Jaeseong Oh
- Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Hye-Jin Boo
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Eun-Sook Yoo
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea
| | - Hee-Kyoung Kang
- Jeju Research Center for Natural Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea; Department of Medicine, College of Medicine, Jeju National University, 102 Jejudaehakno, Jeju, 63243, South Korea.
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Qian H, Ye Z, Hu Y, Chen L, Li L, Qin K, Ye Q, Zuo X. Dahuang-Gancao decoction ameliorates testosterone-induced androgenetic alopecia in mice. JOURNAL OF ETHNOPHARMACOLOGY 2025; 341:119347. [PMID: 39800247 DOI: 10.1016/j.jep.2025.119347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 12/22/2024] [Accepted: 01/08/2025] [Indexed: 01/15/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dahuang-Gancao decoction (DGD) is a traditional Chinese medicinal formula that is recorded in the Synopsis of the Golden Chamber, and is widely used to treat damp-heat in the body. Since the pathological factors of androgenetic alopecia (AGA) also reflect damp-heat blockage, DGD has great potential for the treatment of AGA and has been used effectively in clinical practice. AIM OF THE STUDY The aim of the study was to investigate whether external application of DGD could promote the activation and proliferation of hair follicle stem cells (HFSCs) and improve AGA through the Wnt/β-catenin pathway. MATERIALS AND METHODS The main chemical components of DGD-contained serum were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and database search. Cell Counting Kit-8 (CCK8) was used to investigate the appropriate concentration. Hair regeneration was assessed by hair growth score and histopathological staining. The proliferation of HFSCs and the activation of Wnt/β-catenin pathway were detected by Western blot, immunofluorescence staining, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The AGA mouse model was induced by external application of testosterone (T). Immunofluorescence staining was performed to localize HFSCs by CK15, followed by staining with Ki67, β-catenin, and Cyclin D1, respectively. RESULTS The results illustrated that the 10% DGD group and the 10% DGD + HLY78 group could significantly promote the expression of Wnt10b and β-catenin and the proliferation of HFSCs in vitro, while the 10% DGD + IWR-1 group could reverse the promotion effect of DGD. Animal experiments showed that compared with the model group (T group), DGD promoted hair follicles to enter the anagen phase, as evidenced by an increase in hair growth score, an increase in the number of hair follicles in hematoxylin and eosin (HE) staining, and a significant increase in the ratio of the number of anagen follicles to the total number of hair follicles (AF/AF + TF). In addition, DGD upregulated the expression of Wnt/β-catenin signaling pathway proteins in the skin tissues of AGA mice. It also promoted the proliferation of HFSCs and the expression of β-catenin and Cyclin D1 cytokines in the region of HFSCs. CONCLUSION Both oral and external application of DGD can promote the proliferation of HFSCs by activating the Wnt/β-catenin signalling pathway. External application of DGD can promote the hair follicles to enter the anagen phase, which can ameliorate the symptoms of alopecia in AGA mice. Therefore, compared to oral DGD, external application of DGD is an effective and safer way of administration for the treatment of AGA.
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Affiliation(s)
- Huanzhu Qian
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhen Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Hu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liulin Chen
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Linzhen Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Kaihua Qin
- Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiaobo Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Xiaohong Zuo
- Eye School of Chengdu University of Traditional Chinese Medicine, Ineye Hospital of Chengdu University of Traditional Chinese Medicine, KeyLaboratory of Sichuan Province Ophthalmopathy Prevention & Cureand Visual Function Protection with Traditional Chinese Medicine Laboratory, China.
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Svenskaya YI, Verkhovskii RA, Zaytsev SM, Lademann J, Genina EA. Current issues in optical monitoring of drug delivery via hair follicles. Adv Drug Deliv Rev 2025; 217:115477. [PMID: 39615632 DOI: 10.1016/j.addr.2024.115477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/05/2024] [Accepted: 11/22/2024] [Indexed: 12/09/2024]
Abstract
Drug delivery via hair follicles has attracted much research attention due to its potential to serve for both local and systemic therapeutic purposes. Recent studies on topical application of various particulate formulations have demonstrated a great role of this delivery route for targeting numerous cell populations located in skin and transporting the encapsulated drug molecules to the bloodstream. Despite a great promise of follicle-targeting carriers, their clinical implementation is very rare, mostly because of their poorer characterization compared to conventional topical dosage forms, such as ointments and creams, which have a history spanning over a century. Gathering as complete information as possible on the intrafollicular penetration depth, storage, degradation/metabolization profiles of such carriers and the release kinetics of drugs they contain, as well as their impact on skin health would significantly contribute to understanding the pros and cons of each carrier type and facilitate the selection of the most suitable candidates for clinical trials. Optical imaging and spectroscopic techniques are extensively applied to study dermal penetration of drugs. Current paper provides the state-of-the-art overview of techniques, which are used in optical monitoring of follicular drug delivery, with a special focus on non-invasive in vivo methods. It discusses key features, advantages and limitations of their use, as well as provide expert perspectives on future directions in this field.
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Affiliation(s)
| | | | - Sergey M Zaytsev
- CRAN UMR 7039, Université de Lorraine, Vandoeuvre-lès-Nancy, France
| | - Juergen Lademann
- Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Elina A Genina
- Department of Optics and Biophotonics, Saratov State University, Saratov, Russia
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Kim J, Lee Y, Kim J, Park CW, Song H, Hong J, Lee S, Jung WH, Hong JH, Kim KH, Lee W. Conductive Bio-Harvesting Tonic (CBT) with an Anti-Dandruff Effect Enhances Hair Growth by Utilizing Naturally Generated Electric Energy during Human Activities. J Microbiol Biotechnol 2024; 34:2376-2384. [PMID: 39300961 PMCID: PMC11637866 DOI: 10.4014/jmb.2408.08014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 08/28/2024] [Indexed: 09/22/2024]
Abstract
Alopecia, while not life-threatening, significantly impacts mental health, identity, and self-esteem of those afflicted. Current pharmacological and surgical treatments often have side effects and are limited in their ability to regenerate hair follicles (HF). Therefore, effective solutions for alopecia remain elusive. We developed an innovative hair tonic capable of stimulating HF regeneration by harnessing abandoned electric energy generated during human activities, such as the frictional electric field from walking and the electric fields from electronic devices. We devised a convenient, non-volatile, and conductive hair tonic to capture these naturally occurring electric fields. We identified 6-pentyl-α-pyrone (6PP) from Trichoderma gamsii as an antifungal agent effective against the dandruff-associated fungus Malassezia that can influence alopecia and adopted it into our conductive bio-harvesting tonic (CBT). Testing on hair follicle dermal papilla cells (HFDPC) and SKH1 mice showed that CBT significantly enhanced HF proliferation and increased growth factors in vitro and in vivo. In SKH1 mice, application of CBT under electric stimulation visibly increased hair shaft length and follicle counts. Additionally, tests on actual human hair follicles demonstrated delayed hair follicle regression when electric stimulation and 6PP were applied. In conclusion, our innovative CBT offers a promising and convenient approach for improving hair growth and combating alopecia.
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Affiliation(s)
- Jisun Kim
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Yoonsuk Lee
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jungbum Kim
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Chai Won Park
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | | | - Jinkee Hong
- Barunbio Inc., Seoul 03722, Republic of Korea
- School of Chemical & Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea
| | - Sangmin Lee
- School of Mechanical Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Won Hee Jung
- Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Joo-Hyun Hong
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ki Hyun Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Wonhwa Lee
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
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Kageyama T, Seo J, Yan L, Fukuda J. Effects of oxytocin receptor agonists on hair growth promotion. Sci Rep 2024; 14:23935. [PMID: 39397061 PMCID: PMC11471796 DOI: 10.1038/s41598-024-74962-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 09/30/2024] [Indexed: 10/15/2024] Open
Abstract
Oxytocin has various effects ranging from promoting labor in pregnant women to alleviating stress. Recently, we reported the hair growth-promoting effects of oxytocin in hair follicle organoids. However, its clinical application faces challenges such as rapid degradation in vivo and poor permeability due to its large molecular weight. Therefore, in this study, we investigated the effects of the oxytocin receptor (OXTR) agonists WAY267464 and LIT001 as alternatives to oxytocin on hair growth. Human dermal papilla (DP) cells were cultured in WAY267464 or LIT001-supplemented medium. The addition of WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. We tested the hair growth-promoting effects of WAY267464 and LIT001 using hair follicle organoids in vitro and found that they significantly promoted hair follicle sprouting. Thus, our findings indicate that WAY267464 and LIT001 are potential hair growth agents and may encourage further research on the development of novel hair growth agents targeting OXTR in patients with alopecia.
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Affiliation(s)
- Tatsuto Kageyama
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan
| | - Jieun Seo
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
| | - Lei Yan
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan
| | - Junji Fukuda
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan.
- Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan.
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan.
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11
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Muangsanguan A, Ruksiriwanich W, Linsaenkart P, Jantrawut P, Rachtanapun P, Jantanasakulwong K, Sommano SR, Sringarm K, Arjin C, Sainakham M, Castagnini JM. Synergistic Phytochemical and Pharmacological Actions of Hair Rise TM Microemulsion: A Novel Herbal Formulation for Androgenetic Alopecia and Hair Growth Stimulation. PLANTS (BASEL, SWITZERLAND) 2024; 13:2802. [PMID: 39409672 PMCID: PMC11479085 DOI: 10.3390/plants13192802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/28/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024]
Abstract
Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1-3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.
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Affiliation(s)
- Anurak Muangsanguan
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.M.); (P.L.); (P.J.); (M.S.)
| | - Warintorn Ruksiriwanich
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.M.); (P.L.); (P.J.); (M.S.)
- Cluster of Valorization and Bio-Green Transformation for Translation Research Innovation of Raw Materials and Products, Chiang Mai University, Chiang Mai 50200, Thailand; (S.R.S.); (K.S.)
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
| | - Pichchapa Linsaenkart
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.M.); (P.L.); (P.J.); (M.S.)
| | - Pensak Jantrawut
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.M.); (P.L.); (P.J.); (M.S.)
- Cluster of Valorization and Bio-Green Transformation for Translation Research Innovation of Raw Materials and Products, Chiang Mai University, Chiang Mai 50200, Thailand; (S.R.S.); (K.S.)
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
| | - Pornchai Rachtanapun
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
- School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand
| | - Kittisak Jantanasakulwong
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
- School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand
| | - Sarana Rose Sommano
- Cluster of Valorization and Bio-Green Transformation for Translation Research Innovation of Raw Materials and Products, Chiang Mai University, Chiang Mai 50200, Thailand; (S.R.S.); (K.S.)
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
- Department of Plant and Soil Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Korawan Sringarm
- Cluster of Valorization and Bio-Green Transformation for Translation Research Innovation of Raw Materials and Products, Chiang Mai University, Chiang Mai 50200, Thailand; (S.R.S.); (K.S.)
- Center of Excellence in Agro Bio-Circular-Green Industry (Agro BCG), Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand; (P.R.); (K.J.)
- Department of Animal and Aquatic Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Chaiwat Arjin
- Department of Animal and Aquatic Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Mathukorn Sainakham
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.M.); (P.L.); (P.J.); (M.S.)
| | - Juan M. Castagnini
- Research Group in Innovative Technologies for Sustainable Food (ALISOST), Department of Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine, Faculty of Pharmacy, Universitat de València, Avenida Vicent Andrés Estellés s/n, 46100 Burjassot, Spain;
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12
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Kovale L, Lee S, Song M, Lee J, Son HJ, Sung YK, Kwack MH, Choe W, Kang I, Kim SS, Ha J. Gynostemma pentaphyllum Hydrodistillate and Its Major Component Damulin B Promote Hair Growth-Inducing Properties In Vivo and In Vitro via the Wnt/β-Catenin Pathway in Dermal Papilla Cells. Nutrients 2024; 16:985. [PMID: 38613018 PMCID: PMC11013310 DOI: 10.3390/nu16070985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/21/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Alopecia, a prevalent yet challenging condition with limited FDA-approved treatments which is accompanied by notable side effects, necessitates the exploration of natural alternatives. This study elucidated the hair growth properties of Gynostemma pentaphyllum leaf hydrodistillate (GPHD) both in vitro and in vivo. Furthermore, damulin B, a major component of GPHD, demonstrated hair growth-promoting properties in vitro. Beyond its established anti-diabetic, anti-obesity, and anti-inflammatory attributes, GPHD exhibited hair growth induction in mice parallel to minoxidil. Moreover, it upregulated the expression of autocrine factors associated with hair growth, including VEGF, IGF-1, KGF, and HGF. Biochemical assays revealed that minoxidil, GPHD, and damulin B induced hair growth via the Wnt/β-catenin pathway through AKT signaling, aligning with in vivo experiments demonstrating improved expression of growth factors. These findings suggest that GPHD and damulin B contribute to the hair growth-inducing properties of dermal papilla cells through the AKT/β-catenin signaling pathway.
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Affiliation(s)
- Lochana Kovale
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Seoyeon Lee
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Minhyeok Song
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Jihyun Lee
- Easy Hydrogen Corporation, Jeju City 63196, Republic of Korea;
| | - Hyeong Jig Son
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Young Kwan Sung
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (Y.K.S.); (M.H.K.)
| | - Mi Hee Kwack
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (Y.K.S.); (M.H.K.)
| | - Wonchae Choe
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Insug Kang
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Sung Soo Kim
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
| | - Joohun Ha
- Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (L.K.); (S.L.); (M.S.); (H.J.S.); (W.C.); (I.K.); (S.S.K.)
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13
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Cuevas-Diaz Duran R, Martinez-Ledesma E, Garcia-Garcia M, Bajo Gauzin D, Sarro-Ramírez A, Gonzalez-Carrillo C, Rodríguez-Sardin D, Fuentes A, Cardenas-Lopez A. The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia. Int J Mol Sci 2024; 25:2542. [PMID: 38473791 DOI: 10.3390/ijms25052542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 03/14/2024] Open
Abstract
Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances in its treatment have been hindered. Herein, we review the functional anatomy of hair follicles and the cell signaling events that play a role in follicle cycling. We also discuss the pathology of androgenetic alopecia and the known molecular mechanisms underlying this condition. Additionally, we describe studies comparing the transcriptional differences in hair follicles between balding and non-balding scalp regions. Given the genetic contribution, we also discuss the most significant risk variants found to be associated with androgenetic alopecia. A more comprehensive understanding of this pathology may be generated through using multi-omics approaches.
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Affiliation(s)
- Raquel Cuevas-Diaz Duran
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, NL, Mexico
- CapilarFix®, Monterrey 66220, NL, Mexico
| | - Emmanuel Martinez-Ledesma
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, NL, Mexico
- Tecnologico de Monterrey, Institute for Obesity Research, Monterrey 64849, NL, Mexico
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14
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Kim JH, Kim TY, Goo B, Park Y. Bee Venom Stimulates Growth Factor Release from Adipose-Derived Stem Cells to Promote Hair Growth. Toxins (Basel) 2024; 16:84. [PMID: 38393162 PMCID: PMC10892121 DOI: 10.3390/toxins16020084] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/31/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.
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Affiliation(s)
- Jung Hyun Kim
- Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Republic of Korea
| | - Tae Yoon Kim
- Department of Traditional Korean Medicine Practice, Jaseng Medical Foundation, 538, Gangnam-daero, Gangnam-gu, Seoul 06110, Republic of Korea
| | - Bonhyuk Goo
- Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Republic of Korea
| | - Yeoncheol Park
- Department of Acupuncture & Moxibustion Medicine, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, 26, Kyungheedae-ro 4-gil, Dongdaemun-gu, Seoul 02453, Republic of Korea
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15
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You J, Woo J, Roh KB, Jeon K, Jang Y, Choi SA, Ryu D, Cho E, Park D, Lee J, Jang M, Jung E. Evaluation of efficacy of Silybum marianum flower extract on the mitigating hair loss in vitro and in vivo. J Cosmet Dermatol 2024; 23:529-542. [PMID: 37675655 DOI: 10.1111/jocd.15978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 07/06/2023] [Accepted: 08/20/2023] [Indexed: 09/08/2023]
Abstract
BACKGROUND Natural components that can exert a wide range of anti-hair loss activity with fewer side effects are in high demand. The objective of this study was to investigate the anti-hair loss potential of Silybum marianum flower extract (SMFE) in vitro and in vivo. METHODS The effect of SMFE on dermal papilla cells was evaluated by measuring cell proliferation and VEGF production in hair follicle dermal papilla cells (HFDPCs). In addition, to confirm the effect of SMFE on dermal papilla senescence, SA-β-gal staining and senescence associated secretory phenotype (SASP) production such as IL-6 was observed in both replicative and hydrogen peroxide (H2 O2 )-induced senescence models. In a clinical study, hair growth was determined by reconstitution analysis after shaving the hair of the clinical subject's scalp and hair area. RESULTS SMFE increased the proliferation and VEGF production of HFDPCs. It also suppressed cellular senescence of HFDPCs and IL-6 production in replicative senescence and oxidative stress-induced senescence models. The hair density and total hair count at 16 and 24 weeks after using hair shampoo containing SMFE were significantly increased compared with those of the placebo group. CONCLUSION SMFE has the potential to be used as a natural ingredient for alleviating hair loss.
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Affiliation(s)
- Jiyoung You
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Jieun Woo
- Biospectrum Life Science Institute, Yongin, South Korea
| | | | - Kyungeun Jeon
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Youngsu Jang
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Song-Ah Choi
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Daehoon Ryu
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Eunae Cho
- Biospectrum Life Science Institute, Yongin, South Korea
| | - Deokhoon Park
- Biospectrum Life Science Institute, Yongin, South Korea
| | | | - Min Jang
- Seoul Cosmetics, Incheon, South Korea
| | - Eunsun Jung
- Biospectrum Life Science Institute, Yongin, South Korea
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Rossi A, Caro G. Efficacy of the association of topical minoxidil and topical finasteride compared to their use in monotherapy in men with androgenetic alopecia: A prospective, randomized, controlled, assessor blinded, 3-arm, pilot trial. J Cosmet Dermatol 2024; 23:502-509. [PMID: 37798906 DOI: 10.1111/jocd.15953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/29/2023] [Accepted: 07/29/2023] [Indexed: 10/07/2023]
Abstract
PURPOSE Topical minoxidil (MNX) 2%-5% and oral finasteride (F) 1 mg/day are the only two pharmacological treatments authorized for androgenetic alopecia (AGA). Recently, a 2.2 mg/mL topical formulation of F was developed to minimize the systemic adverse effects associated with the oral formula. MNX and F act through different mechanisms; therefore, their association could improve clinical efficacy. To evaluate the efficacy of the association of 5% MNX and 0.25% topical F compared to their use in monotherapy, a 6-month, prospective, randomized, assessor-blinded trial was conducted. PATIENTS AND METHODS Forty-two males, mean age 24 ± 3 years, with AGA (I-VII of Norwood-Hamilton Grading Scale), treatment naive or free from any therapy for at least 6 months, were enrolled and randomly assigned to three arm treatment groups (2:1:1): group A (n = 19, the subjects applied 5% MNX in the morning and F spray in the evening), group B (n = 12, the subjects applied F spray in the evening), and group C (n = 11, the subjects applied 5% MNX twice daily). The efficacy of treatments was evaluated at baseline and after 3 and 6 months using a global photography score (GPAS; from -3 to +3) and trichoscopy evaluation and assessed by an investigator unaware of treatment allocation. At baseline and after treatments, the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), and testosterone were also evaluated. RESULTS All treatments resulted in an increase in hair density compared to baseline. However, this improvement was significant only for group A (MNX + F), both at three (+56 density/cm2 , p < 0.05) and six (+81 density/cm2 , p < 0.001) months. The mean change from baseline in hair density was higher for group A compared to other groups and statistically different compared to group B (F) (p < 0.01), both after 3 and 6 months. Group A showed a global photographic assessment score (GPAS) significantly higher compared to group B (p < 0.001) and group C (p < 0.05) both at 3 and 6 months (2.0 ± 0.7 vs. 0.6 ± 0.8 and 1.3 ± 0.6; respectively). A significantly greater percentage of subjects in Group A achieved a GPAS score of ≥2 in comparison with Groups B and C both after 3 and 6 months (79% vs. 8% and 41%, respectively). No significant differences were observed in mean hair diameter and hormonal levels between the three groups. Good tolerability was observed in all treated groups. CONCLUSION The association of 5% MNX lotion and 0.25% F in spray formulation in patients with AGA showed a significantly higher clinical and instrumental efficacy compared to the monotherapies, with comparable tolerability and safety profile.
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Affiliation(s)
- Alfredo Rossi
- Dermatologic Clinic Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy
| | - Gemma Caro
- Dermatologic Clinic Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy
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17
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Gupta AK, Talukder M, Shemer A. Efficacy and safety of low-dose oral minoxidil in the management of androgenetic alopecia. Expert Opin Pharmacother 2024; 25:139-147. [PMID: 38315101 DOI: 10.1080/14656566.2024.2314087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 01/31/2024] [Indexed: 02/07/2024]
Abstract
INTRODUCTION Treating alopecia can be challenging. The available treatments are topical minoxidil, low-dose oral minoxidil (LDOM), and 5-α reductase inhibitors like finasteride and dutasteride. Only topical minoxidil and finasteride 1 mg daily are FDA-approved, while the rest are used off-label. Recent research has suggested that oral minoxidil may be a safe and effective treatment for both female androgenetic alopecia (female AGA) and male androgenetic alopecia (male AGA). AREAS COVERED In this review, we explore the pharmacokinetics, mechanism of action, safety, and efficacy of oral minoxidil. Additionally, we discuss its effectiveness compared to other treatments available for female AGA and male AGA. EXPERT OPINION LDOM has demonstrated a favorable efficacy and safety profile in several trials. Subsequently, its use for the treatment of male AGA and female AGA is increasing. However, its use remains off-label, and through increased usage, we will get a better idea of the best dosage and monitoring guidelines. LDOM has also been used with some effectiveness in other forms of hair loss.
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Affiliation(s)
- Aditya K Gupta
- Mediprobe Research Inc, London, ON, Canada
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada
| | - Mesbah Talukder
- Mediprobe Research Inc, London, ON, Canada
- School of Pharmacy, BRAC University, Dhaka, Bangladesh
| | - Avner Shemer
- Department of Dermatology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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18
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Li J, Ge R, Lin K, Wang J, He Y, Lu H, Dong H. Advances in the Application of Microneedles in the Treatment of Local Organ Diseases. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306222. [PMID: 37786290 DOI: 10.1002/smll.202306222] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 09/07/2023] [Indexed: 10/04/2023]
Abstract
In recent years, microneedles (MNs) have attracted a lot of attention due to their microscale sizes and high surface area (500-1000 µm in length), allowing pain-free and efficient drug delivery through the skin. In addition to the great success of MNs based transdermal drug delivery, especially for skin diseases, increasing studies have indicated the expansion of MNs to diverse nontransdermal applications, including the delivery of therapeutics for hair loss, ocular diseases, and oral mucosal. Here, the current treatment of hair loss, eye diseases, and oral disease is discussed and an overview of recent advances in the application of MNs is provided for these three noncutaneous localized organ diseases. Particular emphasis is laid on the future trend of MNs technology development and future challenges of expanding the generalizability of MNs.
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Affiliation(s)
- Jinze Li
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, China
| | - Rujiao Ge
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Kai Lin
- College of Chemistry and Environmental Engineering, Shenzhen University, Guangdong, 518060, China
| | - Junren Wang
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, China
| | - Yu He
- Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK
| | - Huiting Lu
- Department of Chemistry, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Haifeng Dong
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, China
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Mogawer RM, Fawzy MM, Mourad A, Ahmed H, Nasr M, Nour ZA, Hafez V. Topical sodium valproate-loaded nanospanlastics versus conventional topical steroid therapy in alopecia areata: a randomized controlled study. Arch Dermatol Res 2024; 316:64. [PMID: 38170256 PMCID: PMC10764371 DOI: 10.1007/s00403-023-02785-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 10/17/2023] [Accepted: 11/20/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND A myriad of therapeutic modalities for alopecia areata are available; however, none is of high level of evidence, creating an immense need for the evaluation of other treatment modalities, of which topical sodium valproate is of potential role via proposed decrease in beta-catenin breakdown, despite its well-known side effect of hair fall as an oral therapy. OBJECTIVE Evaluating the efficacy and the safety of sodium valproate (SV)-loaded nanospanlastics, in comparison to topical corticosteroids, this is the currently available gold standard topical treatment for patchy AA. METHODOLOGY A total of 66 patients with patchy AA were randomly assigned to receive either topical mometasone furoate lotion or topical SV applied twice daily to all patches except a control patch, which was left untreated. Clinical, trichoscopic and biochemical assessments of beta-catenin tissue levels and Axin-2 gene expression were carried out at baseline and after 3 months. RESULTS Both therapeutic modalities were comparable. Potential efficacy was highlighted by significant improvement in the representative patch, the largest treated patch, to the control patch, the smallest untreated patch in both steroid and valproate groups (p = 0.027, 0.003 respectively). Both beta-catenin levels and Axin-2 gene expression were reduced after treatment, pointing to the inhibitory effect of dominating uncontrolled inflammatory milieu. Baseline beta-catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml (p = - 0.042). CONCLUSION Both topical SV and steroids are of comparable modest efficacy. Thus, further evaluation of SV is due in combination with intralesional steroids and other anti-inflammatory treatment modalities, together with developing individualized approaches based on baseline beta-catenin level. CLINICALTRIALS GOV IDENTIFIER NCT05017454, https://clinicaltrials.gov/ct2/show/NCT05017454 .
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Affiliation(s)
- Rania M Mogawer
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Marwa Mohamed Fawzy
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Mourad
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Heba Ahmed
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Maha Nasr
- Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Zeinab Ahmed Nour
- Biochemistry Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Vanessa Hafez
- Dermatology Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
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20
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Kim D, Lee E, Choi PG, Kim HS, Park SH, Seo HD, Hahm JH, Ahn J, Jung CH. Justicia procumbens prevents hair loss in androgenic alopecia mice. Biomed Pharmacother 2024; 170:115913. [PMID: 38154270 DOI: 10.1016/j.biopha.2023.115913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/08/2023] [Accepted: 11/20/2023] [Indexed: 12/30/2023] Open
Abstract
The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/β-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of β-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3β and β-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss.
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Affiliation(s)
- Daedong Kim
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Eunyoung Lee
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Pyeong Geun Choi
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Hee Soo Kim
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - So-Hyun Park
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Hyo-Deok Seo
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Jeong-Hoon Hahm
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Jiyun Ahn
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Chang Hwa Jung
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea.
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21
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Gupta AK, Talukder M, Shemer A, Piraccini BM, Tosti A. Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review. Skin Appendage Disord 2023; 9:423-437. [PMID: 38376087 PMCID: PMC10806356 DOI: 10.1159/000531890] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 07/06/2023] [Indexed: 02/21/2024] Open
Abstract
Low-dose oral minoxidil (LDOM) has demonstrated a promising safety and efficacy profile in the treatment of various hair disorders, including male androgenetic alopecia (AGA) and female-pattern hair loss (FPHL); however, it lacks FDA approval. The usual LDOM starting dose for male AGA is 1-5 mg/day, depending on physician preference and the patient's condition. For FPHL, it is 0.5-1 mg/day. The maximum dose is generally 5 mg/day. If patients respond well without major side effects, the dose may be gradually increased since the LDOM's efficacy appears to be dose-dependent. Patients may use LDOM long term if the treatment outcome is satisfactory. The common side effects of LDOM are hypertrichosis and cardiovascular symptoms. Females are more prone to hypertrichosis than males. The side effects of LDOM can be categorized as (a) dose-dependent type A side effects (hypertrichosis and cardiovascular symptoms) and (b) idiosyncratic type B side effects (pericardial effusion). Minoxidil acts via multiple pathways. Although minoxidil has a relatively short half-life of around 4 h, its hypotensive effect may last approximately 72 h. Effective treatments for alopecia are limited. Therefore, LDOM could be an important addition to the available therapies for managing some hair disorders, including AGA.
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Affiliation(s)
- Aditya K. Gupta
- Mediprobe Research Inc., London, ON, Canada
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mesbah Talukder
- Mediprobe Research Inc., London, ON, Canada
- School of Pharmacy, BRAC University, Dhaka, Bangladesh
| | - Avner Shemer
- Department of Dermatology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Bianca Maria Piraccini
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Antonella Tosti
- Philip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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22
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Cesarato N, Schwieger-Briel A, Gossmann Y, Henne SK, Hillmann K, Frommherz LH, Wehner M, Xiong X, Thiele H, Oji V, Milani D, Tantcheva-Poor I, Giehl K, Fölster-Holst R, Teichler A, Braeckmans D, Hoeger PH, Jones G, Frank J, Weibel L, Blume-Peytavi U, Hamm H, Nöthen MM, Geyer M, Heilmann-Heimbach S, Basmanav FB, Betz RC. Short anagen hair syndrome: association with mono- and biallelic variants in WNT10A and a genetic overlap with male pattern hair loss. Br J Dermatol 2023; 189:741-749. [PMID: 37671665 DOI: 10.1093/bjd/ljad314] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 08/08/2023] [Accepted: 08/23/2023] [Indexed: 09/07/2023]
Abstract
BACKGROUND Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.
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Affiliation(s)
| | - Agnes Schwieger-Briel
- Department of Pediatric Dermatology, University Children's Hospital Zurich, Zurich, Switzerland
- Department of Dermatology, Medical Center - University of Freiburg, Freiburg, Germany
| | | | | | - Kathrin Hillmann
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Leonie H Frommherz
- Department of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich, Germany
| | | | | | - Holger Thiele
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
| | - Vinzenz Oji
- Department of Dermatology, University Hospital of Muenster, Muenster, Germany
| | - Donatella Milani
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Iliana Tantcheva-Poor
- Department of Dermatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Kathrin Giehl
- Department of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich, Germany
| | - Regina Fölster-Holst
- Department of Dermatology, Venereology and Allergology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Anne Teichler
- Department of Paediatric Dermatology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany
| | - Delphine Braeckmans
- Department of Paediatric Dermatology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany
| | - Peter H Hoeger
- Department of Paediatric Dermatology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany
| | - Gabriela Jones
- Clinical Genetics Department, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Jorge Frank
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Lisa Weibel
- Department of Pediatric Dermatology, University Children's Hospital Zurich, Zurich, Switzerland
| | - Ulrike Blume-Peytavi
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Henning Hamm
- Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany
| | | | - Matthias Geyer
- Institute of Structural Biology, University of Bonn, Medical Faculty and University Hospital Bonn, Bonn, Germany
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23
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Correia M, Lopes J, Lopes D, Melero A, Makvandi P, Veiga F, Coelho JFJ, Fonseca AC, Paiva-Santos AC. Nanotechnology-based techniques for hair follicle regeneration. Biomaterials 2023; 302:122348. [PMID: 37866013 DOI: 10.1016/j.biomaterials.2023.122348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 09/26/2023] [Accepted: 10/05/2023] [Indexed: 10/24/2023]
Abstract
The hair follicle (HF) is a multicellular complex structure of the skin that contains a reservoir of multipotent stem cells. Traditional hair repair methods such as drug therapies, hair transplantation, and stem cell therapy have limitations. Advances in nanotechnology offer new approaches for HF regeneration, including controlled drug release and HF-specific targeting. Until recently, embryogenesis was thought to be the only mechanism for forming hair follicles. However, in recent years, the phenomenon of wound-induced hair neogenesis (WIHN) or de novo HF regeneration has gained attention as it can occur under certain conditions in wound beds. This review covers HF-specific targeting strategies, with particular emphasis on currently used nanotechnology-based strategies for both hair loss-related diseases and HF regeneration. HF regeneration is discussed in several modalities: modulation of the hair cycle, stimulation of progenitor cells and signaling pathways, tissue engineering, WIHN, and gene therapy. The HF has been identified as an ideal target for nanotechnology-based strategies for hair regeneration. However, some regulatory challenges may delay the development of HF regeneration nanotechnology based-strategies, which will be lastly discussed.
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Affiliation(s)
- Mafalda Correia
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Joana Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Daniela Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Ana Melero
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia (Campus de Burjassot), Av. Vicente A. Estelles s/n, 46100, Burjassot, Valencia, Spain
| | - Pooyan Makvandi
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, 324000, Quzhou, Zhejiang, China
| | - Francisco Veiga
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Jorge F J Coelho
- CEMMPRE - Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal
| | - Ana C Fonseca
- CEMMPRE - Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal.
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.
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24
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Starace M, Milan E, Alessandrini A, Bruni F, Piraccini BM. Minoxidil and vitamin E therapy for nail growth disorders: A retrospective study. J Eur Acad Dermatol Venereol 2023; 37:e1226-e1228. [PMID: 37194654 DOI: 10.1111/jdv.19213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/11/2023] [Indexed: 05/18/2023]
Affiliation(s)
- Michela Starace
- Dermatology - IRCCS Policlinico di Sant'Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Elisa Milan
- Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Aurora Alessandrini
- Dermatology - IRCCS Policlinico di Sant'Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Francesca Bruni
- Dermatology - IRCCS Policlinico di Sant'Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Bianca Maria Piraccini
- Dermatology - IRCCS Policlinico di Sant'Orsola - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Bologna, Italy
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25
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Zeng Z, Wang B, Ibrar M, Ying M, Li S, Yang X. Schizochytrium sp. Extracted Lipids Prevent Alopecia by Enhancing Antioxidation and Inhibiting Ferroptosis of Dermal Papilla Cells. Antioxidants (Basel) 2023; 12:1332. [PMID: 37507872 PMCID: PMC10375984 DOI: 10.3390/antiox12071332] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
Alopecia has gradually become a problem that puzzles an increasing number of people. Dermal papilla cells (DPCs) play an important role in hair follicle (HF) growth; thus, exploring the effective chemicals or natural extracts that can remediate the growth of DPCs is vital. Our results showed that Schizochytrium sp.-extracted lipids (SEL) significantly promoted proliferation (up to 1.13 times) and survival ratio (up to 2.45 times) under oxidative stress. The treatment with SEL can protect DPCs against oxidative stress damage, reducing the reactive oxygen species (ROS) level by 90.7%. The relative gene transcription and translation were thoroughly analyzed using RNA-Seq, RT-qPCR, and Western blot to explore the mechanism. Results showed that SEL significantly inhibited the ferroptosis pathway and promoted the expression of antioxidant genes (up to 1.55-3.52 times). The in vivo application of SEL improved hair growth, with the length of new hair increasing by 16.7% and the length of new HF increasing by 92.6%, and the period of telogen shortening increased by 40.0%. This study proposes a novel therapeutic option for alopecia, with the effect and regulation mechanism of SEL on DPC systematically clarified.
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Affiliation(s)
- Zuye Zeng
- Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Boyu Wang
- School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China
| | - Muhammad Ibrar
- Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Ming Ying
- Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
- Innova Bay (Shenzhen) Technology Co., Ltd., Shenzhen 518118, China
| | - Shuangfei Li
- Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Xuewei Yang
- Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
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26
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Kaiser M, Abdin R, Gaumond SI, Issa NT, Jimenez JJ. Treatment of Androgenetic Alopecia: Current Guidance and Unmet Needs. Clin Cosmet Investig Dermatol 2023; 16:1387-1406. [PMID: 37284568 PMCID: PMC10239632 DOI: 10.2147/ccid.s385861] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 05/23/2023] [Indexed: 06/08/2023]
Abstract
Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Traditionally, topical minoxidil and oral finasteride have been the standard of care yielding mixed results. New treatments such as Low-Level Laser Therapy (LLLT), microneedling, platelet-rich plasma (PRP), and others have been extensively studied in the literature, and the purpose of this review is to provide a comprehensive discussion of the latest treatment methods and their efficacy in treating AGA. Novel therapies such as oral minoxidil, topical finasteride, topical spironolactone, botulinum toxin, and stem cell therapy offer interesting alternatives to standard of care therapies for patients. In this review, we present data from recent studies on the clinical efficacy of these treatments. Furthermore, as new treatments have emerged, clinicians have tested combination therapies to assess whether there may be a synergistic relationship between multiple modalities. While there has been a great increase in the treatments available for AGA, the quality of evidence varies greatly and there is still a great need for randomized double blinded clinical trials to adequately assess the clinical efficacy of some treatments. While PRP and LLLT have demonstrated encouraging results, standardized treatment protocols are needed to adequately inform clinicians on how to use such therapies. Given the abundance of new therapeutic options, clinicians and patients must weigh the benefits and risks of each treatment option for AGA.
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Affiliation(s)
- Michael Kaiser
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Rama Abdin
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | - Simonetta I Gaumond
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Naiem T Issa
- Forefront Dermatology, Vienna, VA, USA
- Issa Research and Consulting, LLC, Springfield, VA, USA
| | - Joaquin J Jimenez
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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27
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Lee E, Seo HD, Kim D, Park SH, Kim SR, Hyun C, Hahm JH, Ha TY, Ahn J, Jung CH. Millet seed oil activates β-catenin signaling and promotes hair growth. Front Pharmacol 2023; 14:1172084. [PMID: 37229245 PMCID: PMC10203242 DOI: 10.3389/fphar.2023.1172084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 04/20/2023] [Indexed: 05/27/2023] Open
Abstract
Alopecia, regardless of gender, exacerbates psychological stress in those affected. The rising prevalence of alopecia has fueled a research interest in preventing hair loss. This study investigates the potential of millet seed oil (MSO) in promoting the proliferation of hair follicle dermal papilla cells (HFDPC) and stimulating hair growth in animals with testosterone-dependent hair growth inhibition as part of a study on dietary treatments to improve hair growth. MSO-treated HFDPC significantly increased cell proliferation and phosphorylation of AKT, S6K1, and GSK3β proteins. This induces β-catenin, a downstream transcription factor, to translocate to the nucleus and increase the expression of factors related to cell growth. In a C57BL/6 mice model in which hair growth was inhibited by subcutaneous testosterone injection after shaving the dorsal skin, oral administration of MSO stimulated hair growth in the subject mice by increasing the size and number of hair follicles. These results suggest that MSO is a potent agent that may help prevent or treat androgenetic alopecia by promoting hair growth.
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Affiliation(s)
- Eunyoung Lee
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
| | - Hyo-Deok Seo
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
| | - Daedong Kim
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-Gun, Republic of Korea
| | - So-Hyun Park
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-Gun, Republic of Korea
| | - Soo Ro Kim
- Suheung Research Center, Seongnam-si, Republic of Korea
| | | | - Jeong-Hoon Hahm
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
| | - Tae-Youl Ha
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-Gun, Republic of Korea
| | - Jiyun Ahn
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-Gun, Republic of Korea
| | - Chang Hwa Jung
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-Gun, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-Gun, Republic of Korea
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Kageyama T, Miyata H, Seo J, Nanmo A, Fukuda J. In vitro hair follicle growth model for drug testing. Sci Rep 2023; 13:4847. [PMID: 36964149 PMCID: PMC10038375 DOI: 10.1038/s41598-023-31842-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/17/2023] [Indexed: 03/26/2023] Open
Abstract
In vitro models of human hair follicle-like tissue could be fundamental tools to better understand hair follicle morphogenesis and hair drug screening. During prenatal development and postnatal cyclic hair regeneration, hair follicle morphogenesis is triggered by reciprocal interactions and the organization of the epithelial and mesenchymal cell populations. Given this mechanism, we developed an approach to induce hair peg-like sprouting in organoid cultures composed of epithelial and mesenchymal cells. Human fetal/adult epithelial and mesenchymal cells were cultured in a medium supplemented with a low concentration of either Matrigel or collagen I. These extracellular matrices significantly enhanced the self-organization capabilities of the epithelial and mesenchymal cells, resulting in spherical aggregation and subsequent hair peg-like sprouting. The length of the hair peg sprouting and associated gene expression significantly increased in the presence of a well-known hair drug, minoxidil. This approach may be beneficial for testing hair growth-promoting drug candidates.
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Affiliation(s)
- Tatsuto Kageyama
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan
- Japan Science and Technology Agency (JST)-PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan
| | - Hikaru Miyata
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
| | - Jieun Seo
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
| | - Ayaka Nanmo
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan
| | - Junji Fukuda
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa, 240-8501, Japan.
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan.
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Arora G, Mishra A, Gaurav, Chandra N, Kesharwani P, Jain GK. In Vitro and In Vivo Scalp Retention and Penetration of 99mTc-Minoxidil Solution. J Pharm Sci 2023; 112:230-236. [PMID: 36181874 DOI: 10.1016/j.xphs.2022.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 09/15/2022] [Accepted: 09/15/2022] [Indexed: 10/14/2022]
Abstract
The present study assessed the effect of retention on ex vivo skin and in vivo scalp penetration of radiolabeled minoxidil formulations (5% w/v). Minoxidil was radiolabeled with technetium (99mTc) with an efficiency of 99.1% using 0.2% stannous chloride as reducing agent at pH 6 and incubation temperature of 40 °C. Three different 99mTc-minoxidil formulations were prepared using aqueous ethanolic solution as vehicle. Formulation A contains 99mTc-minoxidil dissolved in vehicle, formulation B contains 10% propylene glycol (PG) and formulation C contains 10% hydroxypropyl cellulose (HPC), in addition. Results showed that addition of HPC resulted in enhanced viscosity (400 mPa.s) and significantly higher ex vivo retention (p < 0.05) and permeation (0.75±0.12%, 8 h). PG does not improve the permeation and the results (0.44±0.05%, 8 h) were not significantly different from vehicle alone (0.40±0.05%, 8 h). The results of the in vivo human scalp studies corroborated with the ex vivo results and addition of hydroxypropyl cellulose (HPH) showed significantly higher (p < 0.05) scalp retention. Post 8 h application, scalp penetration in group treated with formulation C was nearly 2.8-fold and 2.2-fold higher than those treated with formulation A and B, respectively. Further, absence of minoxidil in systemic circulation during study duration indicates safety. In conclusion, our results showed that increasing contact time of minoxidil with scalp by modifying viscosity results in reduced frequency of application and improved efficacy.
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Affiliation(s)
- Gargi Arora
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi 110017, India
| | - Abha Mishra
- Department of Physiology, Vardhman Mahavir Medical College and Safdarjung Hospital, Ansari Nagar, New Delhi 110029, India
| | - Gaurav
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi 110017, India
| | - Nilesh Chandra
- Basic Medical Science Division, Indian Council of Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, New Delhi 110029, India
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Science and Research, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India; Center for Transdisciplinary Research, Department Of Pharmacology, Saveetha Dental College , Saveetha Institute of Medical and Technical science, Chennai , India.
| | - Gaurav Kumar Jain
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi 110017, India; Center for Advanced Formulation Technology, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi 110017, India.
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30
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Colin-Pierre C, El Baraka O, Danoux L, Bardey V, André V, Ramont L, Brézillon S. Regulation of stem cell fate by HSPGs: implication in hair follicle cycling. NPJ Regen Med 2022; 7:77. [PMID: 36577752 PMCID: PMC9797564 DOI: 10.1038/s41536-022-00267-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 11/30/2022] [Indexed: 12/29/2022] Open
Abstract
Heparan sulfate proteoglycans (HSPGs) are part of proteoglycan family. They are composed of heparan sulfate (HS)-type glycosaminoglycan (GAG) chains covalently linked to a core protein. By interacting with growth factors and/or receptors, they regulate numerous pathways including Wnt, hedgehog (Hh), bone morphogenic protein (BMP) and fibroblast growth factor (FGF) pathways. They act as inhibitor or activator of these pathways to modulate embryonic and adult stem cell fate during organ morphogenesis, regeneration and homeostasis. This review summarizes the knowledge on HSPG structure and classification and explores several signaling pathways regulated by HSPGs in stem cell fate. A specific focus on hair follicle stem cell fate and the possibility to target HSPGs in order to tackle hair loss are discussed in more dermatological and cosmeceutical perspectives.
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Affiliation(s)
- Charlie Colin-Pierre
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France.
- BASF Beauty Care Solutions France SAS, Pulnoy, France.
| | | | - Louis Danoux
- BASF Beauty Care Solutions France SAS, Pulnoy, France
| | | | - Valérie André
- BASF Beauty Care Solutions France SAS, Pulnoy, France
| | - Laurent Ramont
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France
- CHU de Reims, Service Biochimie-Pharmacologie-Toxicologie, Reims, France
| | - Stéphane Brézillon
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France
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Kang JI, Choi YK, Han SC, Kim HG, Hong SW, Kim J, Kim JH, Hyun JW, Yoo ES, Kang HK. Limonin, a Component of Immature Citrus Fruits, Activates Anagen Signaling in Dermal Papilla Cells. Nutrients 2022; 14:nu14245358. [PMID: 36558517 PMCID: PMC9787355 DOI: 10.3390/nu14245358] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/14/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Hair loss remains a significant problem that is difficult to treat; therefore, there is a need to identify safe natural materials that can help patients with hair loss. We evaluated the hair anagen activation effects of limonin, which is abundant in immature citrus fruits. Limonin increased the proliferation of rat dermal papilla cells (rDPC) by changing the levels of cyclin D1 and p27, and increasing the number of BrdU-positive cells. Limonin increased autophagy by decreasing phosphorylated mammalian target of rapamycin levels and increasing the phospho-Raptor, ATG7 and LC3B. Limonin also activated the Wnt/β-catenin pathway by increasing phospho-β-catenin levels. XAV939, a Wnt/β-catenin inhibitor, inhibited these limonin-induced changes, including induced autophagy, BrdU-positive cells, and cell proliferation. Limonin increased the phosphorylated AKT levels in both two-dimensional cultured rDPC and three-dimensional spheroids. Treatment with the PI3K inhibitor wortmannin inhibited limonin-induced proliferation, and disrupted other limonin-mediated changes, including decreased p27, increased BrdU-positive cells, induced autophagy, and increased ATG7 and LC3B levels. Wortmannin also inhibited limonin-induced cyclin D1 and LC3 expression in spheroids. Collectively, these results indicate that limonin can enhance anagen signaling by activating autophagy via targeting the Wnt/β-catenin and/or PI3K/AKT pathways in rDPC, highlighting a candidate nutrient for hair loss treatment.
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Affiliation(s)
- Jung-Il Kang
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Youn Kyoung Choi
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Sang-Chul Han
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Hyeon Gyu Kim
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Seok Won Hong
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Jungeun Kim
- Department of Chemistry & Cosmetics, Jeju National University, Jeju 63243, Republic of Korea
| | - Jae Hoon Kim
- Department of Biotechnology, College of Applied Life Science, SARI, Jeju National University, Jeju 63243, Republic of Korea
- Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Republic of Korea
| | - Jin Won Hyun
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Eun-Sook Yoo
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Hee-Kyoung Kang
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
- Correspondence: ; Tel.: +82-64-754-3846; Fax: +82-64-702-2687
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Elmowafy M, Shalaby K, Alruwaili NK, Elkomy MH, Zafar A, Soliman GM, Salama A, Barakat EH. EthoLeciplex: A new tool for effective cutaneous delivery of minoxidil. Drug Dev Ind Pharm 2022; 48:457-469. [PMID: 36093810 DOI: 10.1080/03639045.2022.2124261] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
This work designates EthoLeciplex, a vesicular system consisting of phospholipid, CTAB, ethanol and water, as an innovative vesicular system for cutaneous/transfollicular minoxidil delivery. Minoxidil loaded EthoLeciplex was fabricated by one-step fabrication process. Formulations were designed to study the effects of drug/phospholipid ratio, CTAB/phospholipid ratio, and ethanol concentration on vesicular size, PDI, surface charge and EE%. The optimized formulation was characterized by in vitro release, drug/excipient compatibility, ex vivo skin permeability and safety. A size of 83.6 ± 7.3 to 530.3 ± 29.4 nm, PDI of 0.214 ± 0.01 to 0.542 ± 0.08, and zeta potential of +31.6 ± 4.8 to +57.4 ± 12.5 mV were observed. Encapsulation efficiency was obtained in its maximum value (91.9 ± 16.2%) at the lowest drug/phospholipid ratio, median CTAB/phospholipid and the highest ethanol concentration. The optimized formulation was consisted of 0.3 as drug/lipid ratio, 1.25 as CTAB/lipid ratio and 30% ethanol concentration and showed responses' values in agreement with the predicted results. DSC studies suggested that EthoLeciplex existed in flexible state with complete incorporation of minoxidil into lipid bilayer. The cumulative amount of minoxidil permeated from EthoLeciplex, conventional liposome and ethanolic solution after 12h were 36.3 ± 1.5 µg/ml, 21 ± 2.0 µg/ml and 55 ± 4.0 µg/ml respectively. Based on the remaining amount, the amount of minoxidil accumulated in different skin layers can be predicted in descending order as follows; EthoLeciplex > conventional liposome > minoxidil solution. EthoLeciplex produced marked disorder in the stratum corneum integrity and swelling with no features of skin toxicity. This new cationic system is a promising carrier for cutaneous/transfollicular drug delivery.
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Affiliation(s)
- Mohammed Elmowafy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, P.O. Box 2014, Saudi Arabia
| | - Khaled Shalaby
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, P.O. Box 2014, Saudi Arabia
| | - Nabil K Alruwaili
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, P.O. Box 2014, Saudi Arabia
| | - Mohammed H Elkomy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, P.O. Box 2014, Saudi Arabia
| | - Ameeduzzafar Zafar
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, P.O. Box 2014, Saudi Arabia
| | - Ghareb M Soliman
- Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Ayman Salama
- Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.,Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Elsaied H Barakat
- Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
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33
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Gupta AK, Talukder M, Williams G. Comparison of oral minoxidil, finasteride, and dutasteride for treating androgenetic alopecia. J DERMATOL TREAT 2022; 33:2946-2962. [PMID: 35920739 DOI: 10.1080/09546634.2022.2109567] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
Background Androgenetic alopecia (AGA) is the most common cause of hair loss, often challenging to treat. While oral finasteride (1 mg/day) is an FDA-approved treatment for male AGA, oral minoxidil and oral dutasteride are not approved yet. However, clinicians have been increasingly using these two drugs off-label for hair loss. Recently, Japan and South Korea have approved oral dutasteride (0.5 mg/day) for male AGA.Efficacy and safety A probable efficacy ranking, in decreasing order, is- dutasteride 0.5 mg/day, finasteride 5 mg/day, minoxidil 5 mg/day, finasteride 1 mg/day, followed by minoxidil 0.25 mg/day. Oral minoxidil predominantly causes hypertrichosis and cardiovascular system (CVS) symptoms/signs in a dose-dependent manner, whereas oral finasteride and dutasteride are associated with sexual dysfunction and neuropsychiatric side effects.Pharmacokinetics and pharmacodynamics The average plasma half-lives of minoxidil, finasteride, and dutasteride are ∼4 hours, ∼4.5 hours, and ∼5 weeks, respectively. Minoxidil acts through multiple pathways to promote hair growth. It has been shown as a vasodilator, an anti-inflammatory agent, a Wnt/β-catenin signaling inducer, and an antiandrogen. Finasteride inhibits 5 α-reductase (5AR) type II isoenzyme, while dutasteride inhibits both type I and type II. Thus, dutasteride suppresses DHT levels more than finasteride in the serum and scalp.
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Affiliation(s)
- A K Gupta
- Mediprobe Research Inc., London, ON, Canada.,Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada
| | - M Talukder
- Mediprobe Research Inc., London, ON, Canada
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Rajendran RL, Gangadaran P, Kwack MH, Oh JM, Hong CM, Sung YK, Lee J, Ahn BC. Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles. World J Stem Cells 2022; 14:527-538. [PMID: 36157528 PMCID: PMC9350621 DOI: 10.4252/wjsc.v14.i7.527] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/19/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dermal papillae (DP) and outer root sheath (ORS) cells play important roles in hair growth and regeneration by regulating the activity of hair follicle (HF) cells. AIM To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) on DP and ORS cells as well as HFs. EVs are known to regulate various cellular functions. However, the effects of hMSC-EVs on hair growth, particularly on human-derived HF cells (DP and ORS cells), and the possible mechanisms underlying these effects are unknown. METHODS hMSC-EVs were isolated and characterized using transmission electron micro scopy, nanoparticle tracking analysis, western blotting, and flow cytometry. The activation of DP and ORS cells was analyzed using cellular proliferation, migration, western blotting, and real-time polymerase chain reaction. HF growth was evaluated ex vivo using human HFs. RESULTS Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane. hMSC-EVs promote the proliferation of DP and ORS cells. Moreover, they translocate β-catenin into the nucleus of DP cells by increasing the expression of β-catenin target transcription factors (Axin2, EP2 and LEF1) in DP cells. Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin (K) differentiation markers (K6, K16, K17, and K75) in ORS cells. Furthermore, treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs. CONCLUSION These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.
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Affiliation(s)
- Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Mi Hee Kwack
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Ji Min Oh
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Chae Moon Hong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Young Kwan Sung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Jaetae Lee
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea.
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Wang X, Liu Y, He J, Wang J, Chen X, Yang R. Regulation of signaling pathways in hair follicle stem cells. BURNS & TRAUMA 2022; 10:tkac022. [PMID: 35795256 PMCID: PMC9250793 DOI: 10.1093/burnst/tkac022] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/07/2022] [Indexed: 11/21/2022]
Abstract
Hair follicle stem cells (HFSCs) reside in the bulge region of the outer root sheath of the hair follicle. They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity. The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions, wound repair and skin regeneration. The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways, such as lymphoid enhancer factor/T-cell factor, Wnt/β-catenin, transforming growth factor-β/bone morphogenetic protein, Notch and Hedgehog. The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied, but many mechanisms are still unclear. This article reviews the regulation of hair follicles, HFSCs and related signaling pathways, with the aims of summarizing previous research results, revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.
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Affiliation(s)
| | | | - Jia He
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China
| | - Jingru Wang
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China
| | - Xiaodong Chen
- Correspondence. Xiaodong Chen, E-mail: ; Ronghua Yang,
| | - Ronghua Yang
- Correspondence. Xiaodong Chen, E-mail: ; Ronghua Yang,
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Extremely Low-Frequency Electromagnetic Fields Increase Cytokines in Human Hair Follicles through Wnt/β-Catenin Signaling. Biomedicines 2022; 10:biomedicines10040924. [PMID: 35453674 PMCID: PMC9024517 DOI: 10.3390/biomedicines10040924] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/16/2022] [Accepted: 04/17/2022] [Indexed: 02/05/2023] Open
Abstract
Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair loss must be developed, and electromagnetic field (EMF) therapy has been proven to be a promising medical treatment in various fields, including hair loss treatment. This study evaluated the effect of extremely low-frequency electromagnetic field (ELF-EMF) intensity and exposure time by analyzing the expression of cytokines and anagen-related molecules, which influence hair activation and growth, in hair bulb spheroid (HBS) and hair follicle (HF) organ cultures. ELF-EMFs did not induce toxicity in the HBSs, as verified via the lactate dehydrogenase (LDH) assay. Moreover, an ELF-EMF intensity of 5–20 G promoted the expression of ALP, versican, β-catenin, and several cytokines (VEGF, PDGF, FGF-10, and ET-1) in HBSs. Immunohistochemical staining showed that ELF-EMF at an intensity of 5–20 G upregulated ALP and β-catenin and decreased TUNEL staining in HBS. Moreover, HFs exposed to ELF-EMF for 60 min exhibited an increase in hair length and a 1.5-fold increase in IL-4, ICAM-1, ALP, and versican mRNA expression compared to the control. Immunohistochemical staining indicated that 60 min of ELF-EMF can increase the expression of ALP and β-catenin and decreases TUNEL staining in organ cultures. Collectively, our results demonstrated that ELF-EMF exposure at a 10 G intensity for 60 min promoted hair shaft growth in HFs due to the effect of cytokines and adhesion molecules via the Wnt/β-catenin pathway. Therefore, ELF-EMF is a promising treatment for hair loss.
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5-Bromo-3,4-dihydroxybenzaldehyde Promotes Hair Growth through Activation of Wnt/β-Catenin and Autophagy Pathways and Inhibition of TGF-β Pathways in Dermal Papilla Cells. Molecules 2022; 27:molecules27072176. [PMID: 35408575 PMCID: PMC9000556 DOI: 10.3390/molecules27072176] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Various studies addressing the increasing problem of hair loss, using natural products with few side effects, have been conducted. 5-bromo-3,4-dihydroxybenzaldehyde (BDB) exhibited anti-inflammatory effects in mouse models of atopic dermatitis and inhibited UVB-induced oxidative stress in keratinocytes. Here, we investigated its stimulating effect and the underlying mechanism of action on hair growth using rat vibrissa follicles and dermal papilla cells (DPCs), required for the regulation of hair cycle and length. BDB increased the length of hair fibers in rat vibrissa follicles and the proliferation of DPCs, along with causing changes in the levels of cell cycle-related proteins. We investigated whether BDB could trigger anagen-activating signaling pathways, such as the Wnt/β-catenin pathway and autophagy in DPCs. BDB induces activation of the Wnt/β-catenin pathway through the phosphorylation of GSG3β and β-catenin. BDB increased the levels of autophagic vacuoles and autophagy regulatory proteins Atg7, Atg5, Atg16L, and LC3B. We also investigated whether BDB inhibits the TGF-β pathway, which promotes transition to the catagen phase. BDB inhibited the phosphorylation of Smad2 induced by TGF-β1. Thus, BDB can promote hair growth by modulating anagen signaling by activating Wnt/β-catenin and autophagy pathways and inhibiting the TGF-β pathway in DPCs.
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Abstract
Pattern hair loss (PHL) is a condition that worsens with time and the only way it can be slowed down is with pharmacological intervention. Pharmacological treatments for PHL, from an evidenced-based perspective with respect to safety and efficacy, are limited to only two drugs, minoxidil and finasteride. However, there are a host of drugs being used, off-label with limited evidence. This article attempts to review the literature on this topic, and the authors add to this, with their experience of over two decades on incorporating pharmacologic treatments along with hair transplantation in their management of PHL.
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Affiliation(s)
- Sandeep Suresh Sattur
- HAIRREVIVE- Centre for Hair Restoration & Skin Rejuvenation, Santacruz West, Mumbai, Maharashtra, India
| | - Indu Sandeep Sattur
- HAIRREVIVE- Centre for Hair Restoration & Skin Rejuvenation, Santacruz West, Mumbai, Maharashtra, India
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Papukashvili D, Rcheulishvili N, Liu C, Xie F, Tyagi D, He Y, Wang PG. Perspectives on miRNAs Targeting DKK1 for Developing Hair Regeneration Therapy. Cells 2021; 10:2957. [PMID: 34831180 PMCID: PMC8616136 DOI: 10.3390/cells10112957] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 02/08/2023] Open
Abstract
Androgenetic alopecia (AGA) remains an unsolved problem for the well-being of humankind, although multiple important involvements in hair growth have been discovered. Up until now, there is no ideal therapy in clinical practice in terms of efficacy and safety. Ultimately, there is a strong need for developing a feasible remedy for preventing and treating AGA. The Wnt/β-catenin signaling pathway is critical in hair restoration. Thus, AGA treatment via modulating this pathway is rational, although challenging. Dickkopf-related protein 1 (DKK1) is distinctly identified as an inhibitor of canonical Wnt/β-catenin signaling. Thus, in order to stimulate the Wnt/β-catenin signaling pathway, inhibition of DKK1 is greatly demanding. Studying DKK1-targeting microRNAs (miRNAs) involved in the Wnt/β-catenin signaling pathway may lay the groundwork for the promotion of hair growth. Bearing in mind that DKK1 inhibition in the balding scalp of AGA certainly makes sense, this review sheds light on the perspectives of miRNA-mediated hair growth for treating AGA via regulating DKK1 and, eventually, modulating Wnt/β-catenin signaling. Consequently, certain miRNAs regulating the Wnt/β-catenin signaling pathway via DKK1 inhibition might represent attractive candidates for further studies focusing on promoting hair growth and AGA therapy.
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Affiliation(s)
| | | | | | | | | | - Yunjiao He
- School of Medicine, Southern University of Science and Technology, Shenzhen 518000, China; (D.P.); (N.R.); (C.L.); (F.X.); (D.T.)
| | - Peng George Wang
- School of Medicine, Southern University of Science and Technology, Shenzhen 518000, China; (D.P.); (N.R.); (C.L.); (F.X.); (D.T.)
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Feldman PR, Fiebig KM, Piwko C, Mints BM, Brown D, Cahan DJ, Guevara-Aguirre J. Safety and efficacy of ALRV5XR in men with androgenetic alopecia: A randomised, double-blinded, placebo-controlled clinical trial. EClinicalMedicine 2021; 40:101124. [PMID: 34541479 PMCID: PMC8435693 DOI: 10.1016/j.eclinm.2021.101124] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/13/2021] [Accepted: 08/18/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Androgenetic alopecia (AGA) is the most common hair loss disorder seen in men. It can have an early onset but has also been associated with ageing and senescence. It often induces pronounced psychological impact. ALRV5XR, a new hair loss treatment herein evaluated, was designed to target multiple molecular pathways involved in hair growth and hair follicle stem cell biology. The main objectives of the study were the assessment of safety and efficacy profiles of ALRV5XR in men. METHODS This 24-week, parallel randomised, placebo-controlled, double-blinded clinical trial was performed in a USA community clinic. Healthy men (age 22-65) with AGA and belonging to the Hamilton-Norwood (HN) classification I-VII and Fitzpatrick skin type (FST) I-VI, were randomly allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups. Dermatologist assessment, phototrichograms, and blood samples were obtained in a blinded fashion at baseline, 12 and 24 weeks. Subjects were given a masked treatment consisting of oral capsules, shampoo, conditioner, and follicle serum, which was intended for daily use. Efficacy was assessed via absolute and per cent changes in terminal hair (TH) density, and response rates. The trial was registered with clinicaltrials.gov (NCT04450589) and is completed. FINDINGS Forty-six subjects were enroled in the study, 23 allocated to the ALRV5XR treatment and 23 to the placebo group. Enrolment occurred from April 11 to October 23, 2018. Thirty-six subjects completed the trial (17 ALRV5XR, 19 placebo) and 11 subjects in each group were evaluable for TH outcomes. At 24 weeks, the absolute change in TH density improved by 21·0 THs/cm2 (95% CI: 9·2-32·8; p = 0·0014), and the relative density increased by 16·4% (95% CI: 7·4%-25·5%; p = 0·0012). The odds ratio for being a responder (≥ 0 change) was 87·4. TH density increased linearly and was not affected by HN, FST, ethnicity, age, or body mass index. All subjects in the ALRV5XR group responded to treatment while 81·8% of the placebo group decreased TH density. ALRV5XR induced statistically significant changes in both decrease in vellus hair (VH) density as well as in concomitant increase of the TH/VH ratio when compared to placebo. ALRV5XR was well tolerated, and no adverse events were observed. INTERPRETATION ALRV5XR treatment resulted in clinically significant TH regrowth in men with AGA. Furthermore, it appeared to reverse the characteristic hair miniaturisation seen in this condition. When compared to results of published trials of standard therapy, ALRV5XR showed a multi-fold increase both in efficacy and in response rates. In addition, the continuance of TH regrowth from 12 to 24 weeks suggests that the normal structure and function of non-productive telogen follicles is restored and that a normal hair phenotype may be attained by extended ALRV5XR treatment. FUNDING Arbor Life Labs.
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Affiliation(s)
- Peter R Feldman
- Arbor Life Labs, Toronto, Ontario, Canada
- Corresponding author.
| | - Klaus M Fiebig
- Arbor Life Labs, Toronto, Ontario, Canada
- Corresponding author.
| | | | | | - Dennis Brown
- Valent Technologies, Menlo Park, California, USA
| | | | - Jaime Guevara-Aguirre
- Universidad San Francisco de Quito (USFQ), Quito, Ecuador
- Institute of Endocrinology, Metabolism, and Reproduction (IEMYR), Quito, Ecuador
- Maastricht University, Maastricht, the Netherlands
- College of Medicine, University of Florida, Gainesville, Florida, USA
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Serruya R, Maor Y. Hair growth-promotion effects at the cellular level and antioxidant activity of the plant-based extract Phyllotex™. Heliyon 2021; 7:e07888. [PMID: 34522800 PMCID: PMC8426528 DOI: 10.1016/j.heliyon.2021.e07888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 07/07/2021] [Accepted: 08/25/2021] [Indexed: 11/29/2022] Open
Abstract
Hair loss and predominantly female hair loss is a common dermatologic condition with serious psychosocial consequences. Effective treatments remain scarce mainly due to the multifactorial elements involved in the onset of this chronic condition. The approved drugs available are based on molecules designed towards a single pharmacological target and do not interact with the various biochemical mechanisms involved in alopecia. Phytochemical compounds and their derivatives represent a plethora of biologically active agents, which act in synergism and simultaneously activate different biochemical pathways. Here we present an herbal formulation composed of herbs, vitamins, and minerals acting on hair regrowth and hair micro vascularization. This study aimed at evaluating the potential of Phyllotex™ to treat multifactorial androgenetic alopecia (AGA) in males and females, as well as delving into its molecular mechanisms of action. In vitro studies showed that the herbal formula stimulates cell proliferation of both dermal papilla and HaCaT cells and increases the phosphorylated form of the extracellular signal-regulated kinase 1 and 2 (ERK1/2), a well-known marker for cell proliferation. Surprisingly, expression of TGF-β1 was significantly suppressed without blocking DHT production. Additionally, the formula was able to rescue cells from the oxidative stress conditions generated by 2,2′-Azobis (2-amidinopropane) dihydrochloride (AAPH), a high oxidative agent. This data supports the potential use of this formulation as a hair growth-promoting agent for the treatment of both male and female AGA due to its multifactorial composition, which grants it the ability to cope with the different mechanisms involved in alopecia.
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Affiliation(s)
- Raphael Serruya
- Phytor Lab for Drug Development, Hadassah Medical Center Hebrew University Biotechnology Park (JBP), Ein Kerem Campus, Jerusalem 91120, Israel
| | - Yehoshua Maor
- Phytor Lab for Drug Development, Hadassah Medical Center Hebrew University Biotechnology Park (JBP), Ein Kerem Campus, Jerusalem 91120, Israel
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Abstract
Topical minoxidil (5% foam, 5% solution, and 2% solution) is FDA-approved for androgenetic alopecia (AGA) in men and women.Mechanism of action: Minoxidil acts through multiple pathways (vasodilator, anti-inflammatory agent, inducer of the Wnt/β-catenin signaling pathway, an antiandrogen), and may also affect the length of the anagen and telogen phases.Pharmacokinetics: Approximately 1.4% of topical minoxidil is absorbed through the skin. Minoxidil is a prodrug that is metabolized by follicular sulfotransferase to minoxidil sulfate (active form). Those with higher sulfotransferase activity may respond better than patients with lower sulfotransferase activity.Clinical efficacy (topical minoxidil): In a five-year study, 2% minoxidil exhibited peak hair growth in males at year one with a decline in subsequent years. Topical minoxidil causes hair regrowth in both frontotemporal and vertex areas. The 5% solution and foam were not significantly different in efficacy from the 2% solution.Oral and Sublingual minoxidil (not FDA approved; off-label): After 6 months of administration, minoxidil 5 mg/day was significantly more effective than topical 5% and 2% in male AGA. Low-dose 0.5-5 mg/day may also be safe and effective for female pattern hair loss and chronic telogen effluvium. Sublingual minoxidil may be safe and effective in male and female pattern hair loss.
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Affiliation(s)
- A K Gupta
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada.,Mediprobe Research Inc., London, Canada
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Feldman PR, Fiebig KM, Piwko C, Mints BM, Brown D, Cahan DJ, Guevara-Aguirre J. Safety and efficacy of ALRV5XR in women with androgenetic alopecia or telogen effluvium: A randomised, double-blinded, placebo-controlled clinical trial. EClinicalMedicine 2021; 37:100978. [PMID: 34235415 PMCID: PMC8249777 DOI: 10.1016/j.eclinm.2021.100978] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/20/2021] [Accepted: 06/03/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Scalp hair loss (alopecia) in women is a common ageing and senescing condition. It usually presents as androgenetic alopecia (AGA) or telogen effluvium (TE) and often has pronounced psychological consequences. ALRV5XR is a novel treatment aiming to regenerate a normal hair phenotype by targeting multiple molecular pathways linked to hair growth promotion and hair follicle stem cell activation. The primary objectives of this 24-week trial were to evaluate the safety and efficacy of ALRV5XR in terminal hair (TH) regrowth in women with AGA or TE. METHODS This randomised, double-blind, placebo-controlled trial was performed in a USA community clinic. Healthy women 18-65 years of age with AGA or TE of Ludwig classification I-II and Fitzpatrick skin type I-VI were enrolled. They were allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups using a random number table. Masked dermatologist assessments, phototrichograms and blood samples were obtained at baseline, 12 and 24 weeks. Subjects were given a masked treatment regimen of oral capsules, shampoo, conditioner and follicle serum for daily administration. Main outcomes were absolute and per cent changes in TH density and response rates. The trial was registered with clinicaltrials.gov (NCT04450602) and is completed. FINDINGS 46 subjects (23 ALRV5XR, 23 placebo) were enrolled between April 3 and October 20, 2018. Five subjects dropped out and two were non-compliant. Thirty-nine subjects completed the trial (18 ALRV5XR, 21 placebo). At 24 weeks, the absolute change in TH density improved by 30·1THs/cm2 (95% CI: 15·1-45·1; p=0·0002), and the relative density increased by 19·7% (95% CI: 8·0%-31·4%; p=0·0016). The odds ratio for being a responder (≥0 change) was 2·7. Efficacy increased 133% from week 12 to 24. Efficacy outcomes were similar in AGA and TE subjects. 66·7% of the ALRV5XR group responded by regrowing 40THs/cm2 or more hair. No adverse events were reported. INTERPRETATION In women with AGA or TE, ALRV5XR treatment significantly increased hair regrowth without adverse events. ALRV5XR displayed a multi-fold improved efficacy and response rate when compared to published trials of standard therapy. Progressive acceleration of TH regrowth suggests regeneration of the structure and function of non-productive telogen follicles and prolonged treatment may restore a normal hair phenotype.
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Affiliation(s)
- Peter R Feldman
- Arbor Life Labs, Toronto, Ontario, Canada
- Corresponding authors
| | - Klaus M Fiebig
- Arbor Life Labs, Toronto, Ontario, Canada
- Corresponding authors
| | | | | | - Dennis Brown
- Valent Technologies, Menlo Park, California, USA
| | | | - Jaime Guevara-Aguirre
- Universidad San Francisco de Quito (USFQ), Quito, Ecuador
- Institute of Endocrinology, Metabolism, and Reproduction (IEMYR), Quito, Ecuador
- Maastricht University, Maastricht, The Netherlands
- College of Medicine, University of Florida, Gainesville, Florida, USA
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Bejaoui M, Taarji N, Saito M, Nakajima M, Isoda H. Argan (Argania Spinosa) press cake extract enhances cell proliferation and prevents oxidative stress and inflammation of human dermal papilla cells. J Dermatol Sci 2021; 103:33-40. [PMID: 34158211 DOI: 10.1016/j.jdermsci.2021.06.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 06/03/2021] [Accepted: 06/06/2021] [Indexed: 01/16/2023]
Abstract
BACKGROUND Hair follicle undergoes a growth cycle under the regulation of dermal papilla cells. Due to their enormous roles, these fibroblast cells have been used in various in vitro studies as a screening model to evaluate the effect of hair growth regulating agents. OBJECTIVE In the current study, we aim to check the hair growth potential effect of Argan press cake (APC) extracted using 50 or 80 % aqueous ethanol on human hair follicle dermal papilla cells (HFDPCs) and to determine the molecular mechanism. METHODS APC were applied to HFDPCs, then cell proliferation assays, mitochondrial biogenesis assay, and oxidative stress assay were assessed. DNA microarray was performed from the cells treated with our samples and minoxidil. Validation of the results was done using Quantitative Real-Time PCR with primers for hair-growth related genes. GC/MS analysis was used to determine the compounds contained in APC 50 and 80 %. RESULTS APC enhanced cell proliferation along with the stimulation of the ATP content. Additionally, APC had an anti-oxidant activity against H2O2 mediated oxidative stress preventing dermal papilla cell senescence. Consistent with this, global gene profiling analysis showed an activation of hair growth-related pathway, and a downregulation of inflammation- and oxidative stress-related genes by APC extracts. GC/MS analysis revealed that these extracts contained pure fatty acids, derived sugar chains, and pure compounds including tocopherols, squalene, and spinasterol. CONCLUSION Taken together, here we showed that APC extracts had an effect on stimulating hair growth while inhibiting the inflammation and the oxidative stress of HFDPCs and thus can potentially contribute to an anti-hair loss drug development.
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Affiliation(s)
- Meriem Bejaoui
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan; AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
| | - Noamane Taarji
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan; AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan
| | - Masako Saito
- Planning Department R & D Division, ADEKA CORPORATION, Tokyo, Japan
| | - Mitsutoshi Nakajima
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan; AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan
| | - Hiroko Isoda
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan; AIST-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), AIST, University of Tsukuba, Tsukuba, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
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Micro-Current Stimulation Has Potential Effects of Hair Growth-Promotion on Human Hair Follicle-Derived Papilla Cells and Animal Model. Int J Mol Sci 2021; 22:ijms22094361. [PMID: 33921970 PMCID: PMC8122395 DOI: 10.3390/ijms22094361] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/16/2021] [Accepted: 04/20/2021] [Indexed: 11/20/2022] Open
Abstract
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/β-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/β-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.
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Choi YK, Kang JI, Hyun JW, Koh YS, Kang JH, Hyun CG, Yoon KS, Lee KS, Lee CM, Kim TY, Yoo ES, Kang HK. Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells. Biomol Ther (Seoul) 2021; 29:211-219. [PMID: 33518533 PMCID: PMC7921852 DOI: 10.4062/biomolther.2020.169] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/11/2020] [Accepted: 01/06/2021] [Indexed: 02/06/2023] Open
Abstract
Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.
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Affiliation(s)
- Youn Kyung Choi
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Jung-Il Kang
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Jin Won Hyun
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Young Sang Koh
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Ji-Hoon Kang
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Chang-Gu Hyun
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Department of Chemistry & Cosmetics, Jeju National University, Jeju 63243, Republic of Korea
| | - Kyung-Sup Yoon
- Department of Chemistry & Cosmetics, Jeju National University, Jeju 63243, Republic of Korea
| | - Kwang Sik Lee
- DSongpa R&D Center, Coreana Cosmetic Co., Ltd, Cheonan 31041, Republic of Korea
| | - Chun Mong Lee
- DSongpa R&D Center, Coreana Cosmetic Co., Ltd, Cheonan 31041, Republic of Korea
| | - Tae Yang Kim
- DSongpa R&D Center, Coreana Cosmetic Co., Ltd, Cheonan 31041, Republic of Korea
| | - Eun-Sook Yoo
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Hee-Kyoung Kang
- Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.,Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
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Gao L, Gou N, Yao M, Amakye WK, Ren J. Food-derived natural compounds in the management of chronic diseases via Wnt signaling pathway. Crit Rev Food Sci Nutr 2021; 62:4769-4799. [PMID: 33554630 DOI: 10.1080/10408398.2021.1879001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Wnt signaling pathway is an evolutionarily conserved pathway that control embryonic development, adult tissue homeostasis, and pathological processes of organisms throughout life. However, dysregulation of the Wnt signaling is associated with the occurrence of chronic diseases. In comparison with the application of chemical drugs as traditional treatment for chronic diseases, dietary agents have unique advantages, such as less side effects, multiple targets, convenience in accessibility and higher acceptability in long-term intervention. In this review, we summarized current progress in manipulating the Wnt signaling using food components and its benefits in managing chronic diseases. The underlying mechanisms of bioactive food components in the management of the disease progression via the Wnt signaling was illustrated. Then, the review focused on the function of dietary pattern (which might act via combination of foods with multiple nutrients or food ingredients) on targeting Wnt signaling at multiple level. The potential caveats and challenges in developing new strategy via modulating Wnt-associated diseases with food-based agents and appropriate dietary pattern are also discussed in detail. This review shed light on the understanding of the regulatory effect of food bioactive components on chronic diseases management through the Wnt signaling, which can be expanded to other specific signaling pathway associated with disease.
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Affiliation(s)
- Li Gao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Na Gou
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Maojin Yao
- Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - William Kwame Amakye
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Jiaoyan Ren
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
- Research Institute for Food Nutrition and Human Health, Guangzhou, China
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In Vitro Hair Dermal Papilla Cells Induction by Fagraea berteroana, a Tree of the Marquesan Cosmetopoeia (French Polynesia). COSMETICS 2021. [DOI: 10.3390/cosmetics8010013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Fagraea berteroana is a tree used in traditional medicine in various islands of the South Pacific. Here, we studied its hair growth-inducing properties as suggested by one of its Marquesan ethno-uses in haircare. The ethyl acetate extract of the fruits of F. berteroana (FEAE) and four resulting fractions (FEAE-F0, FEAE-F1, FEAE-F2, and FEAE-F3) were tested on hair follicle dermal papilla cells to determine their cell proliferative activity. Furthermore, RT-qPCR analysis enabled gene modulation analysis, while immunostaining of the β-catenin protein was used to follow protein regulation. We found that the plant extracts induced a controlled, dose-dependent cell proliferation. FEAE-F0 simultaneously down-regulated Bone Morphogenetic Protein 2 (BMP2) mRNA expression and upregulated Cyclin-D1 (CCND1) gene expression, which suggests an involvement in the regulation of the Wnt and Transforming Growth Factor beta (TGFβ) pathways that control the hair cycle. FEAE-F0 exhibited a 1.34-fold increase of nuclear β-catenin protein. This is indicative of an active hair growth state. Thus, we conclude that FEAE-F0 could be an innovative candidate in hair care, which opens interesting leads to promote the Marquesan cosmetopoeia.
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Sho C, Kawano K, Kurata R, Yoshimoto M, Okuno H. Hair growth-promoting activity of components derived from sweet potato shochu. J Biosci Bioeng 2021; 131:405-411. [PMID: 33431342 DOI: 10.1016/j.jbiosc.2020.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 12/03/2020] [Accepted: 12/10/2020] [Indexed: 11/30/2022]
Abstract
Sweet potato shochu oil is one of the by-products of sweet potato shochu production. We investigated the functionality and industrial use of shochu oil as a food-derived raw material. Because of the increased incidence of self-consciousness in people owing to thinning hair, in this study, we examined the hair growth-inducing effects of shochu oil. Minoxidil, the only topical medication approved for hair growth treatment in Japan, was used as a control for the evaluation of hair growth-promoting activity of shochu oil. Human follicle dermal papilla cells treated with shochu oil showed upregulated expression of vascular endothelial growth factor in a concentration-dependent manner, indicating that shochu oil induced the activation of the hair growth cycle. In vivo, epidermal treatment with shochu oil also promoted hair growth in C3H mice. More than 35 components were detected in shochu oil via gas chromatography-mass spectrometry. The main components, accounting for 98.5% of shochu oil, were as follows, in order of decreasing concentration: ethyl palmitate, ethyl linoleate, ethyl oleate, ethyl stearate, ethyl caprate, ethyl laurate, ethyl myristate, and ethyl α-linolenate. Among these, ethyl palmitate, ethyl linoleate, and ethyl α-linolenate promoted hair growth in C3H mice. These results indicate that shochu oil can be used as a hair restorer. To the best of our knowledge, this study is the first to demonstrate the hair growth-promoting activity of shochu oil.
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Affiliation(s)
- Cho Sho
- Kirishima Shuzou Co., Ltd., 4-28-1 Shimokawahigashi, Miyakonojo, Miyazaki 885-8588, Japan.
| | - Kuniaki Kawano
- Kirishima Shuzou Co., Ltd., 4-28-1 Shimokawahigashi, Miyakonojo, Miyazaki 885-8588, Japan
| | - Rie Kurata
- Kyushu Okinawa Agricultural Research Center, National Agriculture and Food Research Organization (NARO), 6651-2 Yokoichi, Miyakonojo, Miyazaki 885-0091, Japan
| | - Makoto Yoshimoto
- My Food Development Research Institute, 109-3 Ichimanjyo, Miyakonojo, Miyazaki 885-0041, Japan
| | - Hironori Okuno
- Kirishima Shuzou Co., Ltd., 4-28-1 Shimokawahigashi, Miyakonojo, Miyazaki 885-8588, Japan
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The microfollicle: a model of the human hair follicle for in vitro studies. In Vitro Cell Dev Biol Anim 2020; 56:847-858. [PMID: 33170472 DOI: 10.1007/s11626-020-00513-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023]
Abstract
Access to complex in vitro models that recapitulate the unique markers and cell-cell interactions of the hair follicle is rather limited. Creation of scalable, affordable, and relevant in vitro systems which can provide predictive screens of cosmetic ingredients and therapeutic actives for hair health would be highly valued. In this study, we explore the features of the microfollicle, a human hair follicle organoid model based on the spatio-temporally defined co-culture of primary cells. The microfollicle provides a 3D differentiation platform for outer root sheath keratinocytes, dermal papilla fibroblasts, and melanocytes, via epidermal-mesenchymal-neuroectodermal cross-talk. For assay applications, microfollicle cultures were adapted to 96-well plates suitable for medium-throughput testing up to 21 days, and characterized for their spatial and lineage markers. The microfollicles showed hair-specific keratin expression in both early and late stages of cultivation. The gene expression profile of microfollicles was also compared with human clinical biopsy samples in response to the benchmark hair-growth compound, minoxidil. The gene expression changes in microfollicles showed up to 75% overlap with the corresponding gene expression signature observed in the clinical study. Based on our results, the cultivation of the microfollicle appears to be a practical tool for generating testable insights for hair follicle development and offers a complex model for pre-clinical substance testing.
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