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Dong XQ, Zhang YH, Luo J, Li MJ, Ma LQ, Qi YT, Miao YL. Keratin 1 modulates intestinal barrier and immune response via kallikrein kinin system in ulcerative colitis. World J Gastroenterol 2025; 31:102070. [PMID: 39958441 PMCID: PMC11752705 DOI: 10.3748/wjg.v31.i6.102070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 12/19/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND External factors in ulcerative colitis (UC) exacerbate colonic epithelial permeability and inflammatory responses. Keratin 1 (KRT1) is crucial in regulating these alterations, but its specific role in the progression of UC remains to be fully elucidated. AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC. METHODS A KRT1 antibody concentration gradient test, along with a dextran sulfate sodium (DSS)-induced animal model, was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system (KKS) and the cleavage of bradykinin (BK)/high molecular weight kininogen (HK) in UC. RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation, induced apoptosis, reduced HK expression, and increased BK expression. It further downregulated intestinal barrier proteins, including occludin, zonula occludens-1, and claudin, and negatively impacted the coagulation factor XII. These changes led to enhanced activation of BK and HK cleavage, thereby intensifying KKS-mediated inflammation in UC. In the DSS-induced mouse model, administration of KRT1 antibody mitigated colonic injury, increased colon length, alleviated weight loss, and suppressed inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-α. It also facilitated repair of the intestinal barrier, reducing DSS-induced injury. CONCLUSION KRT1 inhibits BK expression, suppresses inflammatory cytokines, and enhances markers of intestinal barrier function, thus ameliorating colonic damage and maintaining barrier integrity. KRT1 is a viable therapeutic target for UC.
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Affiliation(s)
- Xiang-Qian Dong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ying-Hui Zhang
- Department of Gastroenterology, Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Mao-Juan Li
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Lan-Qing Ma
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ya-Ting Qi
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
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Radu A, Tit DM, Endres LM, Radu AF, Vesa CM, Bungau SG. Naturally derived bioactive compounds as precision modulators of immune and inflammatory mechanisms in psoriatic conditions. Inflammopharmacology 2025; 33:527-549. [PMID: 39576422 PMCID: PMC11842495 DOI: 10.1007/s10787-024-01602-z] [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: 10/24/2024] [Accepted: 11/01/2024] [Indexed: 02/22/2025]
Abstract
Psoriasis represents a chronic autoimmune skin condition defined by various clinical forms, including inverse, erythrodermic, pustular, guttate, plaque types. While current therapies, including topical treatments but also systemic through conventional synthetic drugs and biologics, have improved symptom management, no treatment completely cures the disease, and numerous options are linked to considerable adverse effects, including immunosuppression and carcinogenic risks. Therefore, there is growing interest in bioactive compounds from natural sources due to their potential to reduce inflammation and oxidative stress in psoriasis with fewer adverse effects. The present narrative review aimed to address the limitations of current psoriasis therapies by exploring the therapeutic potential of bioactive compounds in the classes of flavonoids, terpenoids, omega-3 fatty acids, and alkaloids assessed through complex experimental models, focusing on their immunomodulatory and anti-inflammatory properties. Recent studies highlight the efficacy of natural bioactive compounds in reducing psoriasis symptoms, either as standalone treatments or in combination with conventional therapies. While these compounds show promise in alleviating psoriasis-related inflammation, further research is needed to optimize their therapeutic use, understand their mechanisms of action, and assess long-term safety. Future studies should focus on clinical trials to establish standardized protocols for incorporating bioactive compounds into psoriasis management and explore their potential role in personalized treatment strategies. Continued research is essential to develop more effective, safer, and affordable therapeutic options for psoriasis patients.
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Affiliation(s)
- Ada Radu
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028, Oradea, Romania
| | - Delia Mirela Tit
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028, Oradea, Romania
| | - Laura Maria Endres
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania
- Department of Psycho-Neurosciences and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073, Oradea, Romania
| | - Andrei-Flavius Radu
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania.
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073, Oradea, Romania.
| | - Cosmin Mihai Vesa
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania.
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073, Oradea, Romania.
| | - Simona Gabriela Bungau
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087, Oradea, Romania
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028, Oradea, Romania
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Gao JF, Li TX, Zhang GQ. Myricetin enhances keratinocytes differentiation via TRPV4 channel activation in mouse primary keratinocytes. Int J Immunopathol Pharmacol 2025; 39:3946320251317287. [PMID: 39907058 PMCID: PMC11795610 DOI: 10.1177/03946320251317287] [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: 08/22/2024] [Accepted: 01/16/2025] [Indexed: 02/06/2025] Open
Abstract
The skin serves as the primary defensive barrier of the human body against external stimuli and damage. Keratinocytes, which are the predominant cell type in the human epidermis, undergo a differentiation process that is crucial for the formation of the skin barrier. Myricetin, a dietary flavonoid present in various fruits and vegetables, is known to play a significant role in maintaining intestinal barrier function; however, its impact on the skin barrier remains inadequately understood. Consequently, this study investigates the effects of myricetin on the differentiation of epidermal keratinocytes and the integrity of the skin barrier. Differentiation of primary mouse keratinocytes was induced using 1.8 mM CaCl2. tudy demonstrated that myricetin effectively suppresses cell proliferation and induces both cell cycle arrest and calcium ion (Ca2+) influx, without influencing apoptosis. Concurrently, myricetin enhances the expression of differentiation markers, including K10, TGase1, Filaggrin, and Involucrin, and facilitates the formation of tight junctions. Upon examining the underlying mechanisms, we discovered that myricetin activates the TRPV4 channel, and the promotion of keratinocyte differentiation by myricetin is contingent upon the activation of this channel. In summary, these findings suggested that myricetin could promote keratinocytes differentiation and have well-established skin barrier protective function.
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Affiliation(s)
- Jie-Fang Gao
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
- Subcenter of National Clinical Research Center for Skin and Immune Diseases, Shijiazhuang, Hebei Province, China
- Hebei Technical Innovation Center of Dermatology and Medical Cosmetology Technology, Hebei Province, China
- Central Laboratory, The First Hospital of HeBei Medical University, Shijiazhuang, Hebei Province, China
| | - Tong-Xuan Li
- Central Laboratory, The First Hospital of HeBei Medical University, Shijiazhuang, Hebei Province, China
| | - Guo-Qiang Zhang
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
- Subcenter of National Clinical Research Center for Skin and Immune Diseases, Shijiazhuang, Hebei Province, China
- Hebei Technical Innovation Center of Dermatology and Medical Cosmetology Technology, Hebei Province, China
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Yadav T, Yadav HKS, Raizaday A, Alam MS. The treatment of psoriasis via herbal formulation and nano-polyherbal formulation: A new approach. BIOIMPACTS : BI 2024; 15:30341. [PMID: 40256226 PMCID: PMC12008506 DOI: 10.34172/bi.30341] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 06/27/2024] [Accepted: 07/02/2024] [Indexed: 04/22/2025]
Abstract
Psoriasis is a chronic condition that can strike at any age. This sickness is associated with inflammatory problems that impact all humans in the world. Psoriasis is more common in Scandinavians than in Asian and African populations due to a combination of factors such as age, gender, geographic location, ethnicity, genetic and environmental factors. Immune stimulation, genetic contribution, antimicrobial peptides, and other significant triggers such as medicines, immunizations, infections, trauma, stress, obesity, alcohol intake, smoking, air pollution, sun exposure, and particular disorders cause psoriasis. Numerous clinical research investigations are now underway, and therapeutic alternatives are available. However, these therapies only improve symptoms and do not accomplish a complete cure; they also have dangerous and undesirable side effects. Natural products have gained popularity recently due to their great effectiveness, safety, and low toxicity. Natural formulations of various nanocarriers like liposomes, lipospheres, nanogels, emulgel, nanostructured lipid carriers, nanosponge, nanofibers, niosomes, nanomiemgel, nanoemulsions, nanospheres, cubosomes, microneedles, nanomicelles, ethosomes, nanocrystals, and foams, have significantly contributed and encouraged advancement in psoriasis disease treatment. These phytochemical-loaded new nanoformulations address several issues associated with natural products in conventional dosage forms, such as instability, poor solubility, and limited bioavailability. This article reviews some of the intriguing phytochemicals, as well as their possible molecular target locations and mechanisms of action, which may assist in the development of more specific and selective antipsoriatic medicines. Exploring and understanding phytochemicals' functions will allow for more site-specific psoriasis treatment techniques. This review concluded the psoriasis disease with phytoconstituent loaded herbal or polyherbal nanocarriers and their mechanistic approach.
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Affiliation(s)
- Tejpal Yadav
- Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India
| | | | - Abhay Raizaday
- Department of Pharmaceutics, College of Pharmacy, JSS Academy of Technical Education, Noida, Uttar Pradesh, India
| | - Md Sabir Alam
- SGT College of Pharmacy, SGT University, Gurgaon-Badli Road Chandu, Budhera, Gurugram, Haryana-122505, India
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Man S, Ma W, Jiang H, Haider A, Shi S, Li X, Wu Z, Song Y. Evaluating the efficacy and mechanisms of Hua-Zhuo-Ning-Fu-Decoction on psoriasis using integrated bioinformatics analysis and metabolomics. JOURNAL OF ETHNOPHARMACOLOGY 2024; 325:117856. [PMID: 38316220 DOI: 10.1016/j.jep.2024.117856] [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: 11/16/2023] [Revised: 01/18/2024] [Accepted: 02/02/2024] [Indexed: 02/07/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hua Zhuo Ning Fu Decoction (HZD) is an empirical prescription from traditional Chinese medicine that shows excellent clinical results for psoriasis patients. Uncertainty lingered over HZD's potential anti-psoriasis mechanisms. AIM OF THE STUDY The study's objective is to investigate the pharmacological processes and therapeutic effects of HZD on psoriasis. MATERIALS AND METHODS In the initial phase of the study, an investigation was conducted to assess the effects of HZD on psoriasis-afflicted mice using an imiquimod (IMQ)-induced murine model. The experimental mice were randomly allocated to different groups, including the IMQ-induced model group, the control group, the HZD therapy groups with varying dosage levels (low, medium, and high), and Dexamethasone (DEX, the positive control medicine) group. Bioinformatics analysis and molecular docking were subsequently employed to identify the primary components and molecular targets associated with the therapeutic action of HZD in the context of psoriasis. Additionally, to find the impacts on metabolite regulation, plasma metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used. It's interesting to note that the combined mechanisms from metabolomics were examined in tandem with the targets. In vivo tests were the last step in validating the potential mechanism. Throughout the trial, the following data were recorded: body weight, psoriasis area and severity index (PASI). The molecular targets connected to HZD's anti-psoriasis activities were revealed using histological examination, western blot (WB), and ELISA investigation. RESULTS In mice induced with IMQ, HZD shown good anti-psoriasis effects in terms of PASI score and epidermal acanthosis. 95 HZD targets and 77 bioactive chemicals connected to psoriasis were found by bioinformatics research; of these, 7 key targets (EPHX2, PLA2G2A, TBXAS1, MAOA, ALDH1A3, ADH1A, and ADH1B) were linked to the mechanisms of HZD, the combination degree of which was finally expressed by the score of docking. In addition, HZD regulated nine metabolites. In line with this, HZD modified three metabolic pathways. Additionally, a combined examination of 7 key targets and 9 metabolites suggested that the metabolism of arachidonic acid might be the key metabolic route, which was identified by ELISA analysis. The in vivo investigation shown that HZD could control cytokines associated to inflammation (IL-10, TGF-β, IL-17A, and IL-23), as well as important antioxidant system markers (ROS, GSH, and MDA). Moreover, HZD controlled iron levels and the expression of ferroptosis-related proteins (ACSL4 and GPX4), suggesting that ferroptosis played a crucial role in this process. CONCLUSIONS Our findings demonstrated the whole mechanism and anti-psoriasis effectiveness of HZD, which will promote its clinical application and aid in the investigation of new bioactive components of HZD against psoriasis.
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Affiliation(s)
- Shuai Man
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Wenke Ma
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Hao Jiang
- Pharmacy School, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Ali Haider
- Department of Allied Health Sciences, The University of Lahore, Gujrat Campus, 50700, Pakistan
| | - Shasha Shi
- Pharmacy School, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Xiao Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Zhuzhu Wu
- Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Yongmei Song
- Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Institute for Literature and Culture of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
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Fan R, Zhang C, Li F, Li B, McCarthy A, Zhang Y, Chen S, Zhang L. Hierarchically Assembled Nanofiber Scaffolds with Dual Growth Factor Gradients Promote Skin Wound Healing Through Rapid Cell Recruitment. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2309993. [PMID: 38326085 PMCID: PMC11005683 DOI: 10.1002/advs.202309993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Indexed: 02/09/2024]
Abstract
To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all-around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold-bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications.
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Affiliation(s)
- Ruyi Fan
- Department of Histology and EmbryologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China
- National Medical Products Administration (NMPA) and Guangdong Medical Products Administration (GDMPA)Key Laboratory for Safety Evaluation of CosmeticsGuangzhou510515China
- Zhejiang Engineering Research Center for Tissue Repair MaterialsWenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang325000China
| | - Chuwei Zhang
- Zhejiang Engineering Research Center for Tissue Repair MaterialsWenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang325000China
- Department of Burn and Plastic SurgeryAffiliated Hospital of Nantong UniversityNantong226001China
| | - Fei Li
- Zhejiang Engineering Research Center for Tissue Repair MaterialsWenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang325000China
- Department of Burn and Plastic SurgeryAffiliated Hospital of Nantong UniversityNantong226001China
| | - Bo Li
- Zhejiang Engineering Research Center for Tissue Repair MaterialsWenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang325000China
- Department of Burn and Plastic SurgeryAffiliated Hospital of Nantong UniversityNantong226001China
| | - Alec McCarthy
- Department of Surgery – TransplantHolland Regenerative Medicine ProgramUniversity of Nebraska Medical CenterOmahaNebraska68105USA
| | - Yi Zhang
- Department of Burn and Plastic SurgeryAffiliated Hospital of Nantong UniversityNantong226001China
| | - Shixuan Chen
- Department of Histology and EmbryologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China
- National Medical Products Administration (NMPA) and Guangdong Medical Products Administration (GDMPA)Key Laboratory for Safety Evaluation of CosmeticsGuangzhou510515China
- Zhejiang Engineering Research Center for Tissue Repair MaterialsWenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang325000China
| | - Lin Zhang
- Department of Histology and EmbryologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China
- National Medical Products Administration (NMPA) and Guangdong Medical Products Administration (GDMPA)Key Laboratory for Safety Evaluation of CosmeticsGuangzhou510515China
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Kim H, Choi MR, Jeon SH, Jang Y, Yang YD. Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis. Int J Mol Sci 2024; 25:2756. [PMID: 38474002 DOI: 10.3390/ijms25052756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 02/23/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.
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Affiliation(s)
- Hyungsup Kim
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
| | - Mi Ran Choi
- Laboratory Animal Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea
| | - Seong Ho Jeon
- Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon 11160, Republic of Korea
| | - Yongwoo Jang
- Department of Pharmacology, College of Medicine, Hanyang University, Seoul 04736, Republic of Korea
| | - Young Duk Yang
- Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon 11160, Republic of Korea
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He K, Wang Z, Liu M, Du W, Yin T, Bai R, Duan Q, Wang Y, Lei H, Zheng Y. Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation. Curr Pharm Des 2024; 30:215-229. [PMID: 38532341 DOI: 10.2174/0113816128288527240108110844] [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: 10/20/2023] [Accepted: 12/27/2023] [Indexed: 03/28/2024]
Abstract
BACKGROUND Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.
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Affiliation(s)
- Ke He
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Ziyang Wang
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Meng Liu
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Wenqian Du
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Tingyi Yin
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Ruimin Bai
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Qiqi Duan
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Yuqian Wang
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Hao Lei
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Yan Zheng
- Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
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Varshney M, Bahadur S. Comprehensive Review on Phytoconstituents-based Nanomedicine for the Treatment of Atopic Dermatitis. Curr Pharm Biotechnol 2024; 25:737-756. [PMID: 37888809 DOI: 10.2174/0113892010245092230922180341] [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: 01/14/2023] [Revised: 06/23/2023] [Accepted: 07/06/2023] [Indexed: 10/28/2023]
Abstract
Atopic dermatitis (AD) is known as a chronic disease characterized by eczematous and pruritus skin lesions. The pathology behind atopic dermatitis etiology is loss of epidermal barrier, which prevents the production of protein filaggrin that can induce T-cell infiltration and inflammation. Treatment of AD is majorly based on limiting skin repair as well as reducing inflammation and itching. There are several remedies available for the treatment of AD, such as Janus kinase and calcineurin inhibitors, topical corticosteroids, and phosphodiesterase-4 inhibitors. The conventional formulations in the market have limited safety and efficacy. Hence, effective treatment of atopic dermatitis requires the development of novel, efficacious, reliable, and specific therapies. Recent research data have revealed that some naturally occurring medicinal plants have potential applications in the management of AD through different mechanisms. The nanotechnology-based therapeutics have gained a lot of attention in the last decade for the improvement in the activity of drugs having low absorption due to poor solubility, thus leading to lesser bioavailability. Therapies based on nanotechnology can be an effective way to overcome these obstacles. Due to their effective propensity to provide better drug diffusion and bioavailability as well as drug targeting potential at the desired site of action, these approaches may have decreased adverse drug effects, better penetration, and enhanced therapeutic efficacy. Hence, this review highlights the potential of phytoconstituents-based novel formulations for the treatment of atopic dermatitis. Furthermore, recent patents on therapeutic approaches to atopic dermatitis have also been briefly described.
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Affiliation(s)
- Mayuri Varshney
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, U.P. India
| | - Shiv Bahadur
- Institute of Pharmaceutical Research, GLA University, Mathura, 281406, U.P. India
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Kim JH, Hong M, Han JH, Ryu BR, Lim YS, Lim JD, Kim CH, Lee SU, Kwon TH. In Vitro and In Vivo Anti-Inflammatory Effects of Cannabidiol Isolated from Novel Hemp ( Cannabis sativa L.) Cultivar Pink Pepper. Molecules 2023; 28:6439. [PMID: 37764215 PMCID: PMC10535604 DOI: 10.3390/molecules28186439] [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: 08/18/2023] [Revised: 08/31/2023] [Accepted: 09/03/2023] [Indexed: 09/29/2023] Open
Abstract
Cannabis sativa L. contains more than 80 cannabinoids, among which cannabidiol (CBD) is the main neuroactive component. We aimed to investigate the anti-inflammatory efficacy of CBD in vitro and in vivo isolated from "Pink pepper", a novel hemp cultivar, by repeating the method of selecting and cultivating individuals with the highest CBD content. We investigated the effects of CBD on inflammatory markers elevated by lipopolysaccharide (LPS) treatment in RAW 264.7 mouse macrophage cells through Western blot and RT-PCR. In addition, we confirmed these effects through the ELISA of inflamed paw tissue of a λ-carrageenan-induced mouse edema model that received an oral administration of CBD. CBD inhibited the LPS-induced phosphorylation of NF-κB and MAPK in RAW 264.7 and exhibited anti-inflammatory effects by participating in these pathways. In our in vivo study, we confirmed that CBD also inhibited the inflammatory mediators of proteins extracted from edematous mouse paw tissue. These results show that CBD isolated from "Pink pepper" exhibits potent anti-inflammatory effects. These anti-inflammatory effects of CBD have pharmacological and physiological significance, highlighting the industrial value of this novel cultivar.
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Affiliation(s)
- Jong-Hui Kim
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
| | - Min Hong
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
| | - Joon-Hee Han
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
| | - Byeong Ryeol Ryu
- Department of Bio-Health Convergence, Graduate School, Kangwon National University, Chuncheon 24341, Republic of Korea; (B.R.R.); (Y.S.L.); (J.D.L.)
| | - Young Seok Lim
- Department of Bio-Health Convergence, Graduate School, Kangwon National University, Chuncheon 24341, Republic of Korea; (B.R.R.); (Y.S.L.); (J.D.L.)
- Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Jung Dae Lim
- Department of Bio-Health Convergence, Graduate School, Kangwon National University, Chuncheon 24341, Republic of Korea; (B.R.R.); (Y.S.L.); (J.D.L.)
- Department of Herbal Medicine Resource, Kangwon National University, Samcheok 25949, Republic of Korea
| | - Chang Hyeug Kim
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
| | - Soo-Ung Lee
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
| | - Tae-Hyung Kwon
- Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon 24232, Republic of Korea; (J.-H.K.); (M.H.); (J.-H.H.); (C.H.K.)
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11
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Liu J, Guo Y, Zhang R, Xu Y, Luo C, Wang R, Xu S, Wei L. Inhibition of TRPV4 remodels single cell polarity and suppresses the metastasis of hepatocellular carcinoma. Cell Death Dis 2023; 14:379. [PMID: 37369706 DOI: 10.1038/s41419-023-05903-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 05/31/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor, frequently causing both intrahepatic and extrahepatic metastases. The overall prognosis of patients with metastatic HCC is poor. Recently, single-cell (sc) polarity is proved to be an innate feature of some tumor cells in liquid phase, and directly involved in the cell adhesion to blood vessel and tumor metastasis. Here, we characterize the maintained sc polarity of HCC cells in a suspension culture, and investigate its roles and regulatory mechanisms during metastasis. We demonstrate that transient receptor potential vanilloid 4 (TRPV4) is a promoting regulator of sc polarity via activating Ca2+-dependent AMPK/MLC/ERM pathway. This attenuates the adhesion of metastatic HCC cells to vascular endothelial cells. The reduction of cancer metastases can result from TRPV4 inhibition, which not only impacts the migration and invasion of tumor cells, but also prevents the adhesion to vascular endothelial cells. Additionally, we discover a brand-new TRPV4 inhibitor called GL-V9 that modifies the degree of sc polarization and significantly decreases the metastatic capacity of HCC cells. Taken together, our data shows that TRPV4 and calcium signal are significant sc polarity regulators in metastatic HCC, and that the pharmacological intervention that results in HCC cells becoming depolarized suggests a promising treatment for cancer metastasis.
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Affiliation(s)
- Jian Liu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China
| | - Yongjian Guo
- School of Biopharmacy, China Pharmaceutical University, #639 Longmian Dadao, Nanjing, The People's Republic of China
| | - Ruitian Zhang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China
| | - Ye Xu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China
| | - Chengju Luo
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China
| | - Rui Wang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China
| | - Shu Xu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China.
| | - Libin Wei
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing, The People's Republic of China.
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12
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Alimohammadi S, Pénzes Z, Horváth D, Gyetvai Á, Bácsi A, Kis NG, Németh Á, Arany J, Oláh A, Lisztes E, Tóth BI, Bíró T, Szöllősi AG. TRPV4 Activation Increases the Expression of CD207 (Langerin) of Monocyte-Derived Langerhans Cells without Affecting their Maturation. J Invest Dermatol 2022; 143:801-811.e10. [PMID: 36502939 DOI: 10.1016/j.jid.2022.10.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 10/20/2022] [Accepted: 10/22/2022] [Indexed: 12/14/2022]
Abstract
Langerhans cells (LCs) are the sole professional antigen-presenting cell normally found in the human epidermal compartment. Research into their physiological role is hindered by the fact that they are invariably activated during isolation from the skin. To overcome this challenge, we turned to a monocyte-derived LC (moLC) model, which we characterized with RNA sequencing, and compared the transcriptome of moLCs with that of donor-matched immature dendritic cells. We found that moLCs express markers characteristic of LC2 cells as well as TRPV4. TRPV4 is especially important in the skin because it has been linked to the conservation of the skin barrier, immunological responses, as well as acute and chronic itch, but we know little about its function on LCs. Our results show that TRPV4 activation increased the expression of Langerin and led to increased intracellular calcium concentration in moLCs. Regarding the functionality of moLCs, we found that TRPV4 agonism had a mitigating effect on their inflammatory responses because it decreased their cytokine production and T-cell activating capability. Because TRPV4 has emerged as a potential therapeutic target in dermatological conditions, it is important to highlight LCs as, to our knowledge, a previously unreported target of these therapies.
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Affiliation(s)
- Shahrzad Alimohammadi
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsófia Pénzes
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary
| | - Dorottya Horváth
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary
| | - Ágnes Gyetvai
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Bácsi
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Nikoletta Gréta Kis
- Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ákos Németh
- Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Doctoral School of Health Sciences, Faculty of Public Health, University of Debrecen, Debrecen, Hungary
| | - József Arany
- Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary; Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Oláh
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Erika Lisztes
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Balázs István Tóth
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamás Bíró
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, Münster, Germany
| | - Attila Gábor Szöllősi
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
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Alesci A, Lauriano ER, Fumia A, Irrera N, Mastrantonio E, Vaccaro M, Gangemi S, Santini A, Cicero N, Pergolizzi S. Relationship between Immune Cells, Depression, Stress, and Psoriasis: Could the Use of Natural Products Be Helpful? MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27061953. [PMID: 35335319 PMCID: PMC8954591 DOI: 10.3390/molecules27061953] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 03/12/2022] [Accepted: 03/15/2022] [Indexed: 12/13/2022]
Abstract
Psoriasis is one of the most widespread chronic inflammatory skin diseases, affecting about 2%-3% of the worldwide adult population. The pathogenesis of this disease is quite complex, but an interaction between genetic and environmental factors has been recognized with an essential modulation of inflammatory and immune responses in affected patients. Psoriatic plaques generally represent the clinical psoriatic feature resulting from an abnormal proliferation and differentiation of keratinocytes, which cause dermal hyperplasia, skin infiltration of immune cells, and increased capillarity. Some scientific pieces of evidence have reported that psychological stress may play a key role in psoriasis, and the disease itself may cause stress conditions in patients, thus reproducing a vicious cycle. The present review aims at examining immune cell involvement in psoriasis and the relationship of depression and stress in its pathogenesis and development. In addition, this review contains a focus on the possible use of natural products, thus pointing out their mechanism of action in order to counteract clinical and psychological symptoms.
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Affiliation(s)
- Alessio Alesci
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Stagno d’Alcontres, 31, 98166 Messina, Italy; (E.R.L.); (S.P.)
- Correspondence: (A.A.); (A.S.); (N.C.)
| | - Eugenia Rita Lauriano
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Stagno d’Alcontres, 31, 98166 Messina, Italy; (E.R.L.); (S.P.)
| | - Angelo Fumia
- Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, 98147 Messina, Italy; (A.F.); (S.G.)
| | - Natasha Irrera
- Department of Clinical and Experimental Medicine—Section of Pharmacology, University of Messina, 98125 Messina, Italy;
| | | | - Mario Vaccaro
- Department of Clinical and Experimental Medicine—Section of Dermatology, University of Messina, 98125 Messina, Italy;
| | - Sebastiano Gangemi
- Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, 98147 Messina, Italy; (A.F.); (S.G.)
| | - Antonello Santini
- Department of Pharmacy, University of Napoli Federico II, 80131 Napoli, Italy
- Correspondence: (A.A.); (A.S.); (N.C.)
| | - Nicola Cicero
- Department of Biomedical and Dental Science and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
- Correspondence: (A.A.); (A.S.); (N.C.)
| | - Simona Pergolizzi
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Stagno d’Alcontres, 31, 98166 Messina, Italy; (E.R.L.); (S.P.)
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Choi MK, Kim J, Park HM, Lim CM, Pham TH, Shin HY, Kim SE, Oh DK, Yoon DY. The DPA-derivative 11S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM 10. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 232:113252. [PMID: 35104780 DOI: 10.1016/j.ecoenv.2022.113252] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 01/24/2022] [Accepted: 01/25/2022] [Indexed: 06/14/2023]
Abstract
11 S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid (DoPE) is a derivative of docosapentaenoic acid, a specialized pro-resolving mediator of inflammation such as lipoxins, resolvins, maresins, and protectins. PM10 is a fine dust particle that induces oxidative stress, DNA damage, inflammation, aging, and cancer. The anti-inflammatory mechanism of DoPE, however, has not yet been elucidated. In these studies, we investigated whether DoPE has anti-inflammatory effects in human keratinocyte HaCaT cells. We demonstrated that DoPE suppressed PM10-induced expressions of IL-6 mRNA and protein in human HaCaT keratinocytes. We also investigated the modulating effects of DoPE on reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK). ROS production, extracellular signal regulated kinase (ERK) phosphorylation, and translocation of nuclear factor-kappa B (NF-kB) p65 and NF-kB activity were suppressed by DoPE in PM10-stimulated HaCaT cells. Collectively, our results demonstrated that DoPE inhibited IL-6 expression by reducing ROS generation, suppressing ERK phosphorylation, and inhibiting translocation of NF-kB p65 and NF-kB activity in PM10-stimulated HaCaT cells, suggesting that DoPE can be useful for the resolution of the inflammation caused by IL-6.
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Affiliation(s)
- Myoung-Kwon Choi
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Jinju Kim
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Hyo-Min Park
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Chae-Min Lim
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Thu-Huyen Pham
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Ha Youn Shin
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea
| | - Seong-Eun Kim
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Deok-Kun Oh
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Do-Young Yoon
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
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15
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Gil TY, Jin BR, An HJ. Peucedanum japonicum Thunberg alleviates atopic dermatitis-like inflammation via STAT/MAPK signaling pathways in vivo and in vitro. Mol Immunol 2022; 144:106-116. [PMID: 35219015 DOI: 10.1016/j.molimm.2022.02.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/26/2022] [Accepted: 02/04/2022] [Indexed: 11/19/2022]
Abstract
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disorder that exhibits clinical relapse. The disruption of the skin barrier increases the symptoms of AD, which is accompanied by a reduction in skin integrity. As an immune barrier, the skin plays a crucial role in regulating the inflammatory responses in AD. In this study, we used murine atopic dermatitis model using 2,4-dinitrochlorobenzen (DNCB), which is one of haptens to disrupt the skin barrier and generate the inflammation. As the small molecule, DNCB is easily penetrate the epidermis and binds to tissue proteins provoking immune responses. We evaluated the effects of an aqueous extract of Peucedanum japonicum Thunberg (PJT) in an experimental model of AD by measuring the mRNA and protein expression of cytokines and their related biomarkers. We examined the dorsal skin lesions, transepidermal water loss (TEWL), scratching behavior, expression of molecules related to skin barrier integrity, and histological changes in a murine model of DNCB- induced AD. We found out the down-regulatory effects of PJT on the AD-like symptoms or inflammatory dorsal lesions. For in vitro study, we used a mixture of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in human keratinocytes. The protein and mRNA expressions of skin barrier molecules and inflammatory markers were measured with western blotting and qRT-PCR assays, respectively. As a result, PJT alleviated the AD-like symptoms, and suppressed the inflammation caused by a TNF-α and IFN-γ in human keratinocytes. The regulatory effects of PJT appeared to be mediated via the mitogen-activated protein kinase (MAPK) and signal transducers and activators of transcription (STAT) signaling pathways both in vivo and in vitro. Altogether, the results indicated that PJT could serve as a promising therapeutic candidate for suppressing AD by inhibiting inflammation and improving the integrity of the skin barrier.
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Affiliation(s)
- Tae-Young Gil
- Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do 26339, Republic of Korea
| | - Bo-Ram Jin
- Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do 26339, Republic of Korea
| | - Hyo-Jin An
- Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do 26339, Republic of Korea.
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Rivera-Yañez CR, Ruiz-Hurtado PA, Mendoza-Ramos MI, Reyes-Reali J, García-Romo GS, Pozo-Molina G, Reséndiz-Albor AA, Nieto-Yañez O, Méndez-Cruz AR, Méndez-Catalá CF, Rivera-Yañez N. Flavonoids Present in Propolis in the Battle against Photoaging and Psoriasis. Antioxidants (Basel) 2021; 10:antiox10122014. [PMID: 34943117 PMCID: PMC8698766 DOI: 10.3390/antiox10122014] [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: 11/13/2021] [Revised: 12/09/2021] [Accepted: 12/17/2021] [Indexed: 12/13/2022] Open
Abstract
The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient's health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.
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Affiliation(s)
- Claudia Rebeca Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico;
| | - Porfirio Alonso Ruiz-Hurtado
- Laboratorio de Toxicología de Productos Naturales, Departamento de Farmacia, IPN, Escuela Nacional de Ciencias Biológicas, Av. Wilfrido Massieu, Gustavo A. Madero 07738, Mexico;
| | - María Isabel Mendoza-Ramos
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Julia Reyes-Reali
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Gina Stella García-Romo
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Glustein Pozo-Molina
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Aldo Arturo Reséndiz-Albor
- Laboratorio de Inmunidad de Mucosas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Salvador Díaz Mirón y Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City 11340, Mexico;
| | - Oscar Nieto-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
| | - Adolfo René Méndez-Cruz
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
| | - Claudia Fabiola Méndez-Catalá
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- División de Investigación y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- Correspondence: (C.F.M.-C.); (N.R.-Y.); Tel.: +52-5522-476-721 (N.R.-Y.)
| | - Nelly Rivera-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico; (M.I.M.-R.); (J.R.-R.); (G.S.G.-R.); (G.P.-M.); (O.N.-Y.); (A.R.M.-C.)
- División de Investigación y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico, Tlalnepantla 54090, Mexico
- Correspondence: (C.F.M.-C.); (N.R.-Y.); Tel.: +52-5522-476-721 (N.R.-Y.)
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Zhao Y, Wang J, Liu X. TRPV4 induces apoptosis via p38 MAPK in human lung cancer cells. Braz J Med Biol Res 2021; 54:e10867. [PMID: 34669779 PMCID: PMC8521542 DOI: 10.1590/1414-431x2021e10867] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 06/22/2021] [Indexed: 02/02/2023] Open
Abstract
Lung cancer is one of the most common cancers worldwide. TRPV4 belongs to the ‘transient receptor potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation, and inflammation. Unlike other TRP superfamily channels, its roles in cancers are unknown. Here, we elucidated the effects of TRPV4 and molecular mechanisms in human lung cancer cells. The levels of TRPV4 were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis was determined by FACS assay. The results demonstrated that low levels of TRPV4 were detected in clinical lung carcinoma specimens. Over-expression of TRPV4 induced cell death and inhibited cell proliferation and migration in A549 cells and H460 cells. Moreover, over-expression of TRPV4 enhanced the activation of p38 MAPK signal pathway. Inhibition of p38 MAPK abolished the effects of TRPV4 on cell proliferation, apoptosis, and migration in A549 cells. Collectively, our findings indicated that TRPV4 induced apoptosis via p38 MAPK in human lung cancer cells and suggested that TRPV4 was a potential target for therapy of human lung cancers.
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Affiliation(s)
- Yanyan Zhao
- Department of Respiratory Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jiaying Wang
- Department of Respiratory Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xuehui Liu
- Department of Respiratory Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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18
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Hwang DH, Koh PO, Kang C, Kim E. Rosa davurica Pall. improves DNCB-induced atopic dermatitis in mice and regulated TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 91:153708. [PMID: 34455178 DOI: 10.1016/j.phymed.2021.153708] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 06/13/2023]
Abstract
PURPOSE Rosa davurica Pall., is mainly distributed in Korea, Japan, northeastern China, southeastern Siberia, and eastern Asia. It has been extensively used to treat various kinds of diseases by reason of the significant antioxidant, antiviral and anti-inflammatory activities. However, the pharmacological mechanism of Rosa davurica Pall. in atopic dermatitis (AD) is still ill defined and poorly understood. This study was to examine the anti-inflammatory effects and its mechanism on AD of Rosa davurica Pall. leaves (RDL). METHODS To evaluate the therapeutic potential of RDL against AD, we have investigated the effects of RDL on the inflammatory reactions and the productions of inflammatory chemokines and cytokines that were induced by tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) in HaCaT cells. Futhermore, we examined the effects of RDL on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB). For the in-vivo studies, RDL extract was topically applied to the dinitrochlorobenzene (DNCB)-induced AD mice, then its therapeutic effect was evaluated physiologically and morphologically. RESULTS After the stimulation of HaCaT cells with TNF-α/IFN-γ, RDL considerably reduced the release of inflammatory mediators such as nitric oxide (NO), PEG2 and other cytokines. RDL also reduced the phosphorylations of MAPK and NF-κB in TNF-α/IFN-γ-stimulated HaCaT cells. In vivo topical application of RDL to DNCB-induced AD mice significantly reduced the dorsal skin and ear thickness, clinical dermatitis severity, and mast cells. Treatment with RDL also markedly decreased the levels of serum IgE, IL-6 and the number of WBCs in the blood. CONCLUSION Our studies indicate that RDL inhibits the AD-like skin lesions by modulating skin inflammation. Consequently, these results suggest that RDL may be served as a possible alternative therapeutic treatment for skin disorder such as AD.
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Affiliation(s)
- Du Hyeon Hwang
- Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea; Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Korea.
| | - Phil-Ok Koh
- Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.
| | - Changkeun Kang
- Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea; Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Korea.
| | - Euikyung Kim
- Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea; Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Korea.
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19
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Jang S, Jang S, Kim SY, Ko J, Kim E, Park JY, Hyung H, Lee JH, Lim SG, Park S, Yi J, Lee HJ, Kim MO, Lee HS, Ryoo ZY. Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes. J Inflamm Res 2021; 14:4299-4312. [PMID: 34511969 PMCID: PMC8415766 DOI: 10.2147/jir.s312963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 08/06/2021] [Indexed: 01/13/2023] Open
Abstract
Purpose Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes. Patients and Methods This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively. Results In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis. Conclusion Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).
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Affiliation(s)
- Soyeon Jang
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Soyoung Jang
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Si-Yong Kim
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Jiwon Ko
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Eungyung Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea
| | - Ji Yeong Park
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Hyejin Hyung
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Jin Hong Lee
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Su-Geun Lim
- School of Life Science, Kyungpook National University, Daegu, Korea
| | - Sijun Park
- School of Life Science, Kyungpook National University, Daegu, Korea
| | - Junkoo Yi
- Gyeongsangbukdo Livestock Research Institute, Yeongju, Korea
| | - Heon-Jin Lee
- Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41940, Korea
| | - Myoung Ok Kim
- Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea
| | - Hyun-Shik Lee
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
| | - Zae Young Ryoo
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
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20
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Yao X, Zhu Z, Manandhar U, Liao H, Yu T, Wang Y, Bian Y, Zhang B, Zhang X, Xie J, Song J. RNA-seq reveal RNA binding protein GNL3 as a key mediator in the development of psoriasis vulgaris by regulating the IL23/IL17 axis. Life Sci 2021; 293:119902. [PMID: 34487784 DOI: 10.1016/j.lfs.2021.119902] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Psoriasis is a systemic chronic inflammatory skin disorder that was prone to recurrence. The RNA binding protein GNL3 has an important function in maintaining the proliferative ability of stem cells, and its overexpression leads to apoptosis. GNL3 is expressed in the epidermis, however, its regulatory mechanism in psoriasis vulgaris is still poorly understood. OBJECTIVE To identify the role of GNL3 in the pathogenesis of psoriasis vulgaris. MATERIALS AND METHODS RNA-seq was performed to obtain the data of genes' expression and splicing events in Hela cells after shGNL3 and shCtrl was transferred. High quality results of differentially expressed genes (DEGs) and alternative splicing events (ASEs) were further attained by quality control and analysis. Through the functional enrichment analysis of DEGs and ASEs, the regulating effect of GNL3 was discussed, and the hypothesis was further confirmed in HaCat cells and psoriasis lesions. RESULTS The mRNA expression of IL23A in Hela cells was upregulated in GNL3 knockdown, and the ratio of ASE occurred in TNFAIP3 was increased. However, in HaCaT cells, the mRNA expression level of IL23A was downregulated in GNL3 knockdown, and the ratio of ASE of TNFAIP3 was decreased. Additionally, the results obtained in HaCaT cells was further validated in the lesional psoriatic skin. CONCLUSION GNL3 takes an important part in the development of psoriasis vulgaris by regulating the IL23/IL17 axis, which may serve as the basis of effective targeted treatment in future.
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Affiliation(s)
- Xiaomin Yao
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China
| | - Zhen Zhu
- Department of orthopedics, Wuhan Union Hospital, Huazhong University of Science and Technology, China
| | - Upasana Manandhar
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China
| | - Han Liao
- Laboratory of General Surgery Department, Wuhan Union Hospital, Huazhong University of Science and Technology, China
| | - Tiexi Yu
- Department of orthopedics, Wuhan Union Hospital, Huazhong University of Science and Technology, China
| | - Yueying Wang
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China
| | - Yawen Bian
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China
| | - Bo Zhang
- Department of orthopedics, Wuhan Union Hospital, Huazhong University of Science and Technology, China
| | - Xuanhong Zhang
- Department of Pathology, Lujiang County Hospital of Traditional Chinese Medicine Hospital, Hefei, Anhui, China
| | - Jun Xie
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China.
| | - Jiquan Song
- Deparment of Dermatology, Zhongnan Hospital, Wuhan University, China.
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21
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A comprehensive review of natural products against atopic dermatitis: Flavonoids, alkaloids, terpenes, glycosides and other compounds. Biomed Pharmacother 2021; 140:111741. [PMID: 34087696 DOI: 10.1016/j.biopha.2021.111741] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/24/2021] [Accepted: 05/11/2021] [Indexed: 12/11/2022] Open
Abstract
Atopic dermatitis (AD) is considered a great challenge for human communities and imposes both physiological and mental burdens on patients. Natural products have widely been used to treat a wide range of diseases, including cancer, gastrointestinal diseases, asthma, neurological disorders, and infections. To seek potential natural products against AD, in the current review, we searched the terms "atopic dermatitis" and "natural product" in Pubmed, Medline, Web of Science，Science Direct, Embase, EBSCO, CINAHL, ACS. The results show that many natural products, especially puerarin, ferulic acid and ginsenosides, cound protect against AD. Meanwhile, we discussed the therapeutic mechanisms and showed that the natural products exert their anti-inflammatory effects by suppressing the quantity and activity of many inflammatory cell types and cytokines, including neutrophils, monocytes, lymphocytes, Langerhans cells, interleukins (ILs, including IL-1α, IL-1β, IL-4), TNF-α, and TSLP, IgE. via inhibition of JAK/STAT, MAPKs and NF-κB signaling pathways, thereby, halting the inflammatory cascade. Future investigations should focus on studies with more reflective of the clinical characteristics and demographics, so as to develop natural products that will be hopefully available for the treatment of human AD disease.
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22
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Yoshioka Y, Kamata Y, Tominaga M, Umehara Y, Yoshida I, Matsuoka N, Takamori K. Extract of Scutellaria baicalensis induces semaphorin 3A production in human epidermal keratinocytes. PLoS One 2021; 16:e0250663. [PMID: 33905439 PMCID: PMC8078742 DOI: 10.1371/journal.pone.0250663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 04/12/2021] [Indexed: 11/18/2022] Open
Abstract
In a disease-state-dependent manner, the histamine-resistant itch in dry skin-based skin diseases such as atopic dermatitis (AD) and xerosis is mainly due to hyperinnervation in the epidermis. Semaphorin 3A (Sema3A) is a nerve repulsion factor expressed in keratinocytes and it suppresses nerve fiber elongation in the epidermis. Our previous studies have shown that Sema3A ointment inhibits epidermal hyperinnervation and scratching behavior and improves dermatitis scores in AD model mice. Therefore, we consider Sema3A as a key therapeutic target for improving histamine-resistant itch in AD and xerosis. This study was designed to screen a library of herbal plant extracts to discover compounds with potential to induce Sema3A in normal human epidermal keratinocytes (NHEKs) using a reporter gene assay, so that positive samples were found. Among the positive samples, only the extract of S. baicalensis was found to consistently increase Sema3A levels in cultured NHEKs in assays using quantitative real-time PCR and ELISA. In evaluation of reconstituted human epidermis models, the level of Sema3A protein in culture supernatants significantly increased by application of the extract of S. baicalensis. In addition, we investigated which components in the extract of S. baicalensis contributed to Sema3A induction and found that baicalin and baicalein markedly increased the relative luciferase activity, and that baicalein had higher induction activity than baicalin. Thus, these findings suggest that S. baicalensis extract and its compounds, baicalin and baicalein, may be promising candidates for improving histamine-resistant itch via the induction of Sema3A expression in epidermal keratinocytes.
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Affiliation(s)
- Yasuko Yoshioka
- Central R&D Laboratory, Kobayashi Pharmaceutical Co. Ltd., Ibaraki, Osaka, Japan
- Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan
| | - Yayoi Kamata
- Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan
| | - Mitsutoshi Tominaga
- Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan
| | - Yoshie Umehara
- Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan
| | - Ikuyo Yoshida
- Central R&D Laboratory, Kobayashi Pharmaceutical Co. Ltd., Ibaraki, Osaka, Japan
| | - Nobuya Matsuoka
- Central R&D Laboratory, Kobayashi Pharmaceutical Co. Ltd., Ibaraki, Osaka, Japan
| | - Kenji Takamori
- Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan
- Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
- * E-mail:
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23
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Xie J, Huang S, Huang H, Deng X, Yue P, Lin J, Yang M, Han L, Zhang DK. Advances in the Application of Natural Products and the Novel Drug Delivery Systems for Psoriasis. Front Pharmacol 2021; 12:644952. [PMID: 33967781 PMCID: PMC8097153 DOI: 10.3389/fphar.2021.644952] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/01/2021] [Indexed: 12/16/2022] Open
Abstract
Psoriasis, an incurable autoimmune skin disease, is one of the most common immune-mediated disorders. Presently, numerous clinical research studies are underway, and treatment options are available. However, these treatments focus on improving symptoms of the disease and fail to achieve a radical cure; they also have certain toxic side effects. In recent years, natural products have increasingly gained attention because of their high efficiency and low toxicity. Despite their obvious therapeutic effects, natural products’ biological activity was limited by their instability, poor solubility, and low bioavailability. Novel drug delivery systems, including liposomes, lipospheres, nanostructured lipid carriers, niosomes, nanoemulsions, nanospheres, microneedles, ethosomes, nanocrystals, and foams could potentially overcome the limitations of poor water solubility and permeability in traditional drug delivery systems. Thus, to achieve a therapeutic effect, the drug can reach the epidermis and dermis in psoriatic lesions to interact with the immune cells and cytokines.
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Affiliation(s)
- Jin Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shengjie Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haozhou Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuan Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Pengfei Yue
- State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ming Yang
- State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ding-Kun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
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24
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Zhang X, Li X, Chen Y, Li B, Guo C, Xu P, Yu Z, Ding Y, Shi Y, Gu J. Xiao-Yin-Fang Therapy Alleviates Psoriasis-like Skin Inflammation Through Suppressing γδT17 Cell Polarization. Front Pharmacol 2021; 12:629513. [PMID: 33935720 PMCID: PMC8087247 DOI: 10.3389/fphar.2021.629513] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/30/2021] [Indexed: 01/20/2023] Open
Abstract
Psoriasis is an immune-mediated chronic inflammatory skin disease primarily mediated by the activation of interleukin (IL)-17-producing T cells. Traditional Chinese Medicine (TCM) represents one of the most effective complementary and alternative medicine (CAM) agents for psoriasis, which provides treasured sources for the development of anti-psoriasis medications. Xiao-Yin-Fang (XYF) is an empirically developed TCM formula that has been used to treat psoriasis patients in Shanghai Changhai Hospital for over three decades. Imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was utilized to investigate the therapeutic effects of XYF by the assessment of disease severity and skin thickness. Flow cytometric assay was performed to explore the influence of XYF on skin-related immunocytes, primarily T cells. And, RNA sequencing analysis was employed to determine the alternation in gene expression upon XYF therapy. We discovered that XYF alleviated psoriasis-like skin inflammation mainly through suppressing dermal and draining lymph-node IL-17-producing γδT (γδT17) cell polarization. Moreover, XYF therapy ameliorated the relapse of psoriasis-like dermatitis and prohibited dermal γδT cell reactivation. Transcriptional analysis suggested that XYF might regulate various inflammatory signaling pathways and metabolic processes. In conclusion, our results clarified the therapeutic efficacy and inner mechanism of XYF therapy in psoriasis, which might promote its clinical application in psoriasis patients and facilitate the development of novel anti-psoriasis drugs based on the bioactive components of XYF.
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Affiliation(s)
- Xilin Zhang
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.,Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xiaorui Li
- Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Youdong Chen
- Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.,Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Bingjie Li
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Chunyuan Guo
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Peng Xu
- Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.,Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zengyang Yu
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Yangfeng Ding
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Jun Gu
- Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.,Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
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25
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Rosenbaum T, Benítez-Angeles M, Sánchez-Hernández R, Morales-Lázaro SL, Hiriart M, Morales-Buenrostro LE, Torres-Quiroz F. TRPV4: A Physio and Pathophysiologically Significant Ion Channel. Int J Mol Sci 2020; 21:ijms21113837. [PMID: 32481620 PMCID: PMC7312103 DOI: 10.3390/ijms21113837] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 05/23/2020] [Accepted: 05/24/2020] [Indexed: 02/07/2023] Open
Abstract
Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.
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Affiliation(s)
- Tamara Rosenbaum
- Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (M.B.-A.); (R.S.-H.); (S.L.M.-L.); (M.H.)
- Correspondence: ; Tel.: +52-555-622-56-24; Fax: +52-555-622-56-07
| | - Miguel Benítez-Angeles
- Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (M.B.-A.); (R.S.-H.); (S.L.M.-L.); (M.H.)
| | - Raúl Sánchez-Hernández
- Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (M.B.-A.); (R.S.-H.); (S.L.M.-L.); (M.H.)
| | - Sara Luz Morales-Lázaro
- Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (M.B.-A.); (R.S.-H.); (S.L.M.-L.); (M.H.)
| | - Marcia Hiriart
- Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (M.B.-A.); (R.S.-H.); (S.L.M.-L.); (M.H.)
| | - Luis Eduardo Morales-Buenrostro
- Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico;
| | - Francisco Torres-Quiroz
- Departamento de Bioquímica y Biología Estructural, División Investigación Básica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico;
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26
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Chiang CC, Cheng WJ, Lin CY, Lai KH, Ju SC, Lee C, Yang SH, Hwang TL. Kan-Lu-Hsiao-Tu-Tan, a traditional Chinese medicine formula, inhibits human neutrophil activation and ameliorates imiquimod-induced psoriasis-like skin inflammation. JOURNAL OF ETHNOPHARMACOLOGY 2020; 246:112246. [PMID: 31539577 DOI: 10.1016/j.jep.2019.112246] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 09/05/2019] [Accepted: 09/16/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Kan-Lu-Hsiao-Tu-Tan (KLHTT) is a popular traditional Chinese medicine for treating various inflammatory diseases. AIM OF THE STUDY The aim of the present study was to investigate the anti-inflammatory effects of KLHTT on human neutrophils and its therapeutic potential in treating imiquimod (IMQ)-induced psoriasis-like skin inflammation. MATERIALS AND METHODS Spectrophotometry, flow cytometry, and microscopy with immunohistochemical staining were used to evaluate superoxide anion generation, elastase release, CD11b expression, adhesion, and neutrophil extracellular trap (NET) formation in activated human neutrophils. Reactive oxygen species (ROS) and reactive nitrogen species in cell-free systems were measured using a multi-well fluorometer or a spectrophotometer. A psoriasis-like skin inflammation was induced in mice using the IMQ cream. RESULTS KLHTT suppressed superoxide anion generation, ROS production, CD11b expression, and adhesion in activated human neutrophils. In contrast, KLHTT failed to alter elastase release in activated human neutrophils. Additionally, KLHTT had an ROS-scavenging effect in the AAPH assay, but it did not scavenge superoxide anions directly in the xanthine/xanthine oxidase assay. Protein kinase C (PKC)-induced NET formation most commonly occurs through ROS-dependent mechanisms. KLHTT significantly inhibited phorbol 12-myristate 13-acetate, a PKC activator, inducing NET formation. Furthermore, topical KLHTT treatment reduced the area affected by psoriasis area and severity index (PASI) score and ameliorated neutrophil infiltration in IMQ-induced psoriasis-like skin inflammation in mice. CONCLUSIONS Our data show that KLHTT has anti-neutrophilic inflammatory effects in inhibiting ROS generation and cell adhesion. KLHTT also mitigated NET formation, mainly via an ROS-dependent pathway. In addition, KLHTT reduced neutrophil infiltration and improved the severity of IMQ-induced psoriasis-like skin inflammation in mice. Therefore, KLHTT may prove to be a safe and effective psoriasis therapy in the future.
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Affiliation(s)
- Chih-Chao Chiang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Supervisory Board, Taoyuan Chinese Medicine Association, Taoyuan, 338, Taiwan; Puxin Fengze Chinese Medicine Clinic, Taoyuan, 326, Taiwan.
| | - Wei-Jen Cheng
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
| | - Cheng-Yu Lin
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
| | - Kuei-Hung Lai
- Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan.
| | - Seanson-Chance Ju
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
| | - Chuan Lee
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
| | - Sien-Hung Yang
- Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
| | - Tsong-Long Hwang
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, 243, Taiwan.
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Hou DD, Zhang W, Gao YL, Sun YZ, Wang HX, Qi RQ, Chen HD, Gao XH. Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis. Int Immunopharmacol 2019; 74:105676. [DOI: 10.1016/j.intimp.2019.105676] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/27/2019] [Accepted: 05/30/2019] [Indexed: 01/30/2023]
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Apoptotic or Antiproliferative Activity of Natural Products against Keratinocytes for the Treatment of Psoriasis. Int J Mol Sci 2019; 20:ijms20102558. [PMID: 31137673 PMCID: PMC6566887 DOI: 10.3390/ijms20102558] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 02/08/2023] Open
Abstract
Natural products or herbs can be used as an effective therapy for treating psoriasis, an autoimmune skin disease that involves keratinocyte overproliferation. It has been demonstrated that phytomedicine, which is used for psoriasis patients, provides some advantages, including natural sources, a lower risk of adverse effects, and the avoidance of dissatisfaction with conventional therapy. The herbal products’ structural diversity and multiple mechanisms of action have enabled the synergistic activity to mitigate psoriasis. In recent years, the concept of using natural products as antiproliferative agents in psoriasis treatment has attracted increasing attention in basic and clinical investigations. This review highlights the development of an apoptotic or antiproliferatic strategy for natural-product management in the treatment of psoriasis. We systematically introduce the concepts and molecular mechanisms of keratinocyte-proliferation inhibition by crude extracts or natural compounds that were isolated from natural resources, especially plants. Most of these studies focus on evaluation through an in vitro keratinocyte model and an in vivo psoriasis-like animal model. Topical delivery is the major route for the in vivo or clinical administration of these natural products. The potential use of antiproliferative phytomedicine on hyperproliferative keratinocytes suggests a way forward for generating advances in the field of psoriasis therapy.
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Huang K, Ma K, Chang Y, Lo L, Jhap T, Su Y, Liu P, Chueh S. Baicalein inhibits matrix metalloproteinase 1 expression via activation of
TRPV
1‐Ca‐
ERK
pathway in ultraviolet B–irradiated human dermal fibroblasts. Exp Dermatol 2019; 28:568-575. [DOI: 10.1111/exd.13912] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/23/2019] [Accepted: 02/18/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Kuo‐Feng Huang
- Division of Plastic Surgery Department of Surgery Chi Mei Medical Center Tainan Taiwan Republic of China
| | - Kuo‐Hsing Ma
- Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan Republic of China
| | - Yen‐Jung Chang
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Liang‐Chuan Lo
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Tian‐You Jhap
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Yu‐Hua Su
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Pei‐Shan Liu
- Department of Microbiology Soochow University Taipei Taiwan Republic of China
| | - Sheau‐Huei Chueh
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
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Aster glehni Extract Containing Caffeoylquinic Compounds Protects Human Keratinocytes through the TRPV4-PPAR δ-AMPK Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2018:9616574. [PMID: 30622619 PMCID: PMC6304624 DOI: 10.1155/2018/9616574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 10/21/2018] [Accepted: 11/12/2018] [Indexed: 11/17/2022]
Abstract
Aster glehni (AG) has been used in cooking and as a medicine to treat various diseases for over hundreds of years in Korea. To speculate the protective effects of AG on skin barrier, we estimated the protein levels of biomarkers related to skin barrier protection in human keratinocytes, HaCaT cells treated with sodium dodecyl sulfate (SDS), or 2,4-dinitrochlorobenzene (DNCB). The protein levels for keratin, involucrin, defensin, tumor necrosis factor alpha (TNFα), peroxisome proliferator-activated receptor delta (PPARδ), 5′ adenosine monophosphate-activated protein kinase (AMPK), serine palmitoyltransferase long chain base subunit 2 (SPTLC2), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were evaluated using western blotting or immunocytochemistry in HaCaT cells. AG extract increased the protein levels of PPARδ, phosphorylated AMPK, SPTLC2, keratin, involucrin, and defensin compared to the SDS or DNCB control group. However, TNFα expression increased by SDS or DNCB was decreased with AG extract. The order of action of each regulatory biomarker in AG pathway was identified TRPV4→PPARδ→AMPK from antagonist and siRNA treatment studies. AG can ameliorate the injury of keratinocytes caused by SDS or DNCB through the sequential regulation of TRPV4→PPARδ→AMPK pathway.
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Wu Y, Liu L, Bian C, Diao Q, Nisar MF, Jiang X, Bartsch JW, Zhong M, Hu X, Zhong JL. MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated ERK signaling in psoriasis. Cell Commun Signal 2018; 16:58. [PMID: 30219085 PMCID: PMC6138911 DOI: 10.1186/s12964-018-0271-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 08/31/2018] [Indexed: 12/16/2022] Open
Abstract
Background The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. Methods Following imiquimod cream (IMQ) application to let-7bTG (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A dual luciferase reporter assay and bioinformatics was carried out to detect target gene of let-7b. Additionally, the differentiation markers were measured. Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and ERK signaling. Results we found let-7bTG inhibits acanthosis and reduces the disease severity by treatment with IMQ compared to wild-type mice. Further study illustrated that let-7b promotes differentiation of keratinocytes in vivo and in vitro. Using bioinformatics and reporter gene assays, we found that IL-6 is a target gene of let-7b. In psoriasis, high expression levels of IL-6 lead to increased acivation of p-ERK1/2. High levels of let-7bTG transgene expression suppresses IL-6 expression and leads to increased keratinocyte differentiation. Moreover, let-7b acts as an upstream negative regulator of the ERK signaling pathway in keratinocytes of psoriasis. Conclusions Our result reveals a previously unknown mechanism for regulation of IL-6 levels during psoriasis by let-7b and highlights a critical role for the ERK1/2 signaling pathway in epidermal differentiation during psoriasis. Trial registration The ethical approval for this study was from the Affiliated Hospital of Medical University of Anhui _ Fast_ PJ2017–11–14. Electronic supplementary material The online version of this article (10.1186/s12964-018-0271-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yan Wu
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China.,Department of Dermatology, Chongqing First People's Hospital and Chongqing Traditional Chinese Medicine Hospital, No. 40 Daomenkou St., District Yuzhong, Chongqing, 400011, China
| | - Liu Liu
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Chunxiang Bian
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Qingchun Diao
- Department of Dermatology, Chongqing First People's Hospital and Chongqing Traditional Chinese Medicine Hospital, No. 40 Daomenkou St., District Yuzhong, Chongqing, 400011, China
| | - Muhammad Farrukh Nisar
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China.,Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, 54000, Pakistan
| | - Xuemei Jiang
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Jörg W Bartsch
- Philipps University Marburg, Department of Neurosurgery, Baldingerstr, 35033, Marburg, Germany
| | - Maojiao Zhong
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Xiangyu Hu
- Department of Dermatology, Chongqing First People's Hospital and Chongqing Traditional Chinese Medicine Hospital, No. 40 Daomenkou St., District Yuzhong, Chongqing, 400011, China
| | - Julia Li Zhong
- The Base of "111 Project" for Biomechanics & Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, college of Bioengineering, Chongqing University, Chongqing, 400044, China. .,Department of Dermatology, Chongqing First People's Hospital and Chongqing Traditional Chinese Medicine Hospital, No. 40 Daomenkou St., District Yuzhong, Chongqing, 400011, China.
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Fang HC, Wu BQ, Hao YL, Luo Y, Zhao HL, Zhang WY, Zhang ZL, Liang JJ, Liu W, Chen XH. KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the activation of the Notch signaling pathway in mouse models. J Cell Physiol 2018; 234:3634-3646. [PMID: 30191968 DOI: 10.1002/jcp.27133] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 07/05/2018] [Indexed: 12/16/2022]
Abstract
Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such as excessive formation of free radicals and also overload of calcium, which lead to cell death, tissue scarring, and remodeling. The current study aims to explore whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in mouse models. Myocardial tissues were used for the determination of the positive rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers as well as myocardial infarction area. The transfected myocardial cells were treated with KRT1-siRNA, Jagged1, and DAPT (inhibitor of Notch-1 signaling pathway). The expression of KRT1, NICD, Hes1, Bcl-2, and Bax protein was detected. The MTT assay was applied for cell proliferation and flow cytometry was used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1 protein expression, apoptosis of myocardial cells, CK and LDH expression, myocardial infarction area, increased expression of MDA, NO, SDH, IL-1, IL-6, TNF-α, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD, NICD, Hes1, and Bcl-2. The downregulation of KRT1 led to decreased expression of KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl-2, decreased cell apoptosis, and improved cell proliferation. The inhibition of the Notch signaling pathway leads to reduced expression of Bax, increased expression of NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell proliferation. Our data conclude that KRT1 silencing is able to make MIRI better by activating the Notch signaling pathway in mice.
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Affiliation(s)
- Hong-Cheng Fang
- Shenzhen Baoan Shajing People's Hospital of Guangzhou Medical University, Shenzhen, China
| | - Bao-Quan Wu
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Yun-Ling Hao
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Ying Luo
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Hong-Lei Zhao
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Wen-Ying Zhang
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Zhi-Ling Zhang
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Jin-Jie Liang
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
| | - Wei Liu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xie-Hui Chen
- Department of Geriatrics and Cardiovascular Medicine, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, China
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Huang K, Ma K, Hung Y, Lo L, Lin K, Liu P, Hu M, Chueh S. A new copper ionophore DPMQ protects cells against ultraviolet B irradiation by inhibiting the TRPV1 channel. J Cell Physiol 2018; 233:9594-9610. [DOI: 10.1002/jcp.26861] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Kuo‐Feng Huang
- Division of Plastic Surgery, Department of Surgery Chi Mei Medical Center Tainan Taiwan Republic of China
| | - Kuo‐Hsing Ma
- Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan Republic of China
| | - Yu‐Chien Hung
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Liang‐Chuan Lo
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Kuo‐Chen Lin
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
| | - Pei‐Shan Liu
- Department of Microbiology Soochow University Taipei Taiwan Republic of China
| | - Ming‐Kuan Hu
- Department of Medicinal Chemistry School of Pharmacy, National Defense Medical Center Taipei Taiwan Republic of China
| | - Sheau‐Huei Chueh
- Department of Biochemistry National Defense Medical Center Taipei Taiwan Republic of China
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Yang JH, Lee E, Lee B, Cho WK, Ma JY, Park KI. Ethanolic Extracts of Artemisia apiacea Hance Improved Atopic Dermatitis-Like Skin Lesions In Vivo and Suppressed TNF-Alpha/IFN-Gamma⁻Induced Proinflammatory Chemokine Production In Vitro. Nutrients 2018; 10:nu10070806. [PMID: 29932162 PMCID: PMC6073925 DOI: 10.3390/nu10070806] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 06/15/2018] [Accepted: 06/19/2018] [Indexed: 12/21/2022] Open
Abstract
Artemisia apiacea Hance is a traditional herbal medicine used for treating eczema and jaundice in Eastern Asia including China, Korea, and Japan. However, the biological and pharmacological actions of Artemisia apiacea Hance in atopic dermatitis (AD) are not fully understood. An ethanolic extract of Artemisia apiacea Hance (EAH) was tested in vitro and in vivo to investigate its anti-inflammatory activity and anti-atopic dermatitis effects. The results showed that EAH dose-dependence inhibited production of regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin (IL)-6, IL-8, and thymus and activation-regulated chemokine (TARC). EAH inhibited the activation of p38, extracellular signal-regulated kinases (ERK), and STAT-1 and suppressed the degradation of inhibited both nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκB-α) in TNF-α/IFN-γ–stimulated HaCaT cells. EAH also suppressed the translocation of inflammation transcription factors such as NF-κB p65 in TNF-α/IFN-γ–stimulated HaCaT cells. In addition, EAH reduced 2,4-dinitrochlorobenzene (DNCB)-induced ear thickness and dorsal skin thickness in a dose-dependent manner. EAH appeared to regulate chemokine formation by inhibiting activation of and ERK as well as the NK-κB pathways. Furthermore, EAH significantly improved the skin p38 conditions in a DNCB-induced AD-like mouse model.
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Affiliation(s)
- Ju-Hye Yang
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
| | - Esther Lee
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
| | - BoHyoung Lee
- ViroMed Co., Ltd., Seoul National University 1, Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
| | - Won-Kyung Cho
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
| | - Jin Yeul Ma
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
| | - Kwang-Il Park
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
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Yang JH, Yoo JM, Lee E, Lee B, Cho WK, Park KI, Yeul Ma J. Anti-inflammatory effects of Perillae Herba ethanolic extract against TNF-α/IFN-γ-stimulated human keratinocyte HaCaT cells. JOURNAL OF ETHNOPHARMACOLOGY 2018; 211:217-223. [PMID: 28970155 DOI: 10.1016/j.jep.2017.09.041] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 09/22/2017] [Accepted: 09/28/2017] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Perillae Herba is a perennial plant that is widely distributed throughout Asia. The leaves of Perillae Herba have been widely used to treat various diseases, such as cold due to wind-cold, headache, cough, abdominal fullness, distention, and fish and crab poisoning. MATERIALS AND METHODS To assess the anti-inflammatory activity of Perillae Herba leaf ethanolic extract (PHE) in human keratinocytes, we measured the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-induced mRNA expression and production of proinflammatory chemokines such as thymus and activation-regulated chemokines; regulated on activation, normal T cell expressed and secreted; interleukin (IL)-6; and IL-8 in HaCaT cells. We evaluated the ability of PHE to decrease the expression of proinflammatory marker proteins, such as mitogen-activated protein kinase (MAPK), STAT-1, and NK-κB, using western blot analysis and immunocytochemistry. RESULTS PHE inhibited activation of p38, ERK, and JNK and suppressed the phosphorylation of STAT-1 and NK-κB in TNF-α/IFN-γ-stimulated HaCaT cells. PHE also suppressed chemokine mRNA and protein levels in TNF-α/IFN-γ-stimulated HaCaT cells. PHE appears to regulate chemokine formation by inhibiting activation of MAPK, as well as the STAT-1 and NK-κB pathways. CONCLUSIONS PHE suppresses the expression and production of TNF-α/IFN-γ-stimulated proinflammatory chemokines by blocking NF-κB, STAT-1, and MAPK activation.
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Affiliation(s)
- Ju-Hye Yang
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea
| | - Jae-Myung Yoo
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea
| | - Esther Lee
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea
| | - BoHyoung Lee
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea
| | - Won-Kyung Cho
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea
| | - Kwang-Il Park
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea.
| | - Jin Yeul Ma
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea.
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Pharmacological activation of TRPV4 produces immediate cell damage and induction of apoptosis in human melanoma cells and HaCaT keratinocytes. PLoS One 2018; 13:e0190307. [PMID: 29293584 PMCID: PMC5749757 DOI: 10.1371/journal.pone.0190307] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 12/12/2017] [Indexed: 12/11/2022] Open
Abstract
Background TRPV4 channels are calcium-permeable cation channels that are activated by several physicochemical stimuli. Accordingly, TRPV4 channels have been implicated in the regulation of osmosensing, mechanotransduction, thermosensation, and epithelial/endothelial barrier functions. Whether TRPV4 is also mechanistically implicated in melanoma cell proliferation is not clear. Here, we hypothesized that TRPV4 is expressed in human melanoma and that pharmacological activation interferes with cell proliferation. Methodology/Principal findings TRPV4 functions were studied in melanoma cell lines (A375, SK-MEL-28, MKTBR), immortalized non-cancer keratinocytes (HaCaT), and murine 3T3 fibroblasts by patch-clamp, qRT-PCR, intracellular calcium measurements, cell proliferation, and flow cytometric assays of apoptosis and cell cycle. The selective TRPV4-activator, GSK1016790A, elicited non-selective cation currents with TRPV4-typical current-voltage-relationship in all cell lines. GSK1016790A-induced currents were blocked by the TRPV4-blocker, HC067047. TRPV4 mRNA expression was demonstrated by qRT-PCR. In A375 cells, TRPV4 activation was frequently paralleled by co-activation of calcium/calmodulin-regulated KCa3.1 channels. Light microscopy showed that TRPV4-activation produced rapid cellular disarrangement, nuclear densification, and detachment of a large fraction of all melanoma cell lines and HaCaT cells. TRPV4-activation induced apoptosis and drastically inhibited A375 and HaCaT proliferation that could be partially prevented by HC067047. Conclusions/Significance Our study showed that TRPV4 channels were functionally expressed in human melanoma cell lines and in human keratinocytes. Pharmacological TRPV4 activation in human melanoma cells and keratinocytes caused severe cellular disarrangement, necrosis and apoptosis. Pharmacological targeting of TRPV4 could be an alternative or adjuvant therapeutic strategy to treat melanoma progression and other proliferative skin disorders.
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Yang HJ, Kim MJ, Kang S, Moon NR, Kim DS, Lee NR, Kim KS, Park S. Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice. JOURNAL OF ETHNOPHARMACOLOGY 2017; 199:97-105. [PMID: 28159725 DOI: 10.1016/j.jep.2017.01.055] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 11/24/2016] [Accepted: 01/30/2017] [Indexed: 06/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. MATERIALS AND METHODS HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured. RESULTS Chlorogenic acid (129.6±10.2μg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3μg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3μg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice. CONCLUSION SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD.
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Affiliation(s)
- Hye Jeong Yang
- Division of Strategic Food Industry Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea.
| | - Min Jung Kim
- Division of Nutrition and Metabolism Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea.
| | - Suna Kang
- Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea.
| | - Na Rang Moon
- Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea.
| | - Da Sol Kim
- Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea.
| | - Na Ra Lee
- Department of Nanobiomechatronics, Hoseo University, Asan, South Korea.
| | - Kang Sung Kim
- Department of Food Science and Nutrition, Yong In University, South Korea.
| | - Sunmin Park
- Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea.
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