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Biomedicine & Pharmacotherapy =... Jun 2023Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese...
Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese medicine, is primarily used for the clinical treatment of AD. In this study, a 2,4-dinitrochlorobenzene-induced AD BALB/c mouse model was established, and a comprehensive pharmacological method was used to determine the pharmacological effects and molecular mechanisms of PAF in the treatment of AD. The results indicated that both PAF gel (PAFG) and PAFG+MF (mometasone furoate) attenuated the severity of AD and reduced the infiltration of eosinophils and mast cells in the skin. Serum metabolomics showed that PAFG combined with MF administration exerted a synergistic effect by remodeling metabolic disorders in mice. In addition, PAFG also alleviated the side effects of thymic atrophy and growth inhibition induced by MF. Network pharmacology predicted that the active ingredients of PAF were flavonoids and exerted therapeutic effects through anti-inflammatory effects. Finally, immunohistochemical analysis confirmed that PAFG inhibited the inflammatory response through the ERβ/HIF-1α/VEGF signaling pathway. Our results revealed that PAF can be used as a natural-source drug with good development prospects for the clinical treatment of AD.
Topics: Mice; Animals; Dermatitis, Atopic; Physalis; Plant Extracts; Flavonoids; Hormones
PubMed: 37003035
DOI: 10.1016/j.biopha.2023.114622 -
Biological & Pharmaceutical Bulletin 2018Juniperus chinensis, commonly Chinese juniper, has been used for treating inflammatory diseases. This study aimed to investigate anti-atopic dermatitis (AD) effects of...
Juniperus chinensis, commonly Chinese juniper, has been used for treating inflammatory diseases. This study aimed to investigate anti-atopic dermatitis (AD) effects of standardized J. chinensis fruits extract on murine oxazolone- and 2,4-dinitrochlorobenzene (DNCB)-induced models of AD. Ear swelling, epidermis thickening, and eosinophils infiltration in the oxazolone-mediated dermatitis of BALB/c mice were significantly reduced upon topical application of J. chinensis fruits 95% EtOH extract (JCE). Besides, transdermal administration of JCE to SKH-1 hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing transepidermal water loss and improving skin hydration. Decreased total serum immunoglobulin E (IgE) and interleukin (IL)-4 levels could be observed in atopic dorsal skin samples of JCE-treated group. According to the phytochemical analysis, JCE was found to contain isoscutellarein-7-O-β-D-xyloside, cupressuflavone, and amentoflavone as main compounds. Therapeutic attempts with the J. chinensis fruits might be useful in the treatment of AD and related skin inflammatory diseases.
Topics: Adjuvants, Immunologic; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biflavonoids; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Flavonoids; Fruit; Glycosides; Immunoglobulin E; Interleukin-4; Irritants; Juniperus; Mice, Hairless; Mice, Inbred BALB C; Molecular Structure; Oxazolone; Phytotherapy; Plant Extracts; Republic of Korea; Skin
PubMed: 29386485
DOI: 10.1248/bpb.b17-00818 -
Acta Pharmacologica Sinica Nov 2020Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of...
Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of S1P receptor type 2 (S1P) in a mouse model of atopic dermatitis, which was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) on ventral skin on D0, followed by repeated DNCB challenge on both ears from D7 to D49. Wild-type mice with atopic dermatitis displayed severe inflammation and mast cell accumulation in ear tissues and elevated IgE levels in serum. Furthermore, the mice showed significantly increased sizes of draining lymph nodes, high levels of inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in the ears and lymph nodes and high levels of chemokines CCL17 and CCL22 in ears. Administration of JTE-013, a selective antagonist of S1P (3 mg/kg, i.p, from D19 to D49) before DNCB challenge significantly suppressed DNCB-induced atopic responses in ears and lymph nodes. JTE-013 administration also significantly decreased the lymph nodes sizes, the levels of inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in the ears and lymph nodes, and the levels of chemokines CCL17 and CCL22 in ears. Furthermore, the inflammatory responses of atopic dermatitis were greatly ameliorated in S1pr2 gene-deficient mice. As CCL17 and CCL22 are CCR4 ligands, acting as Th2-attracting chemokines, we investigated CCL17 and CCL22 expression in bone marrow-derived dendritic cells (BMDCs) from wild-type and S1pr2 gene-deficient mice. Addition of IL-4 (10 ng/mL) markedly increased the levels of CCL17 and CCL22, but IL-4-induced CCL17 and CCL22 expression was significantly blunted in BMDCs from S1pr2 gene-deficient mice. Furthermore, pretreatment with JTE-013 (1-30 μM) dose-dependently suppressed this induction in BMDCs from wild-type mice. Our results demonstrate that blockage of S1P ameliorates not only DNCB-induced atopic dermatitis symptoms but also Th2 cell-attracting capacity of dendritic cells, suggesting S1P as a potential therapeutic target for atopic dermatitis.
Topics: Animals; Chemokine CCL17; Chemokine CCL22; Dermatitis, Atopic; Dinitrochlorobenzene; Ear; Lymph Nodes; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Pyrazoles; Pyridines; Sphingosine-1-Phosphate Receptors
PubMed: 32457418
DOI: 10.1038/s41401-020-0412-8 -
Annals of Translational Medicine May 2022This study aimed to explore the mechanism of Bacillus Calmette-Guerin polysaccharide and nucleic acid injection (BCG-PSN) targeting the transient receptor potential...
Study on the intervention effect and mechanism of bacillus Calmette-Guerin polysaccharide and nucleic acid injection on atopic dermatitis by targeting the transient receptor potential vanilloid subtype 1 pathway.
BACKGROUND
This study aimed to explore the mechanism of Bacillus Calmette-Guerin polysaccharide and nucleic acid injection (BCG-PSN) targeting the transient receptor potential vanilloid subtype 1 (TRPV1) pathway for atopic dermatitis (AD) in mice.
METHODS
Experiment 1: a total of 30 Kunming (KM) mice were randomized into blank control, model, BCG-PSN low-dose (25 g/kg), BCG-PSN medium-dose (75 g/kg), BCG-PSN high-dose (225 g/kg), and positive drug (hydrocortisone 25 mg/kg) control groups. The AD model mice were established by induction with 2,4-Dinitrochlorobenzene (DNCB). After treatment in groups, the symptom score and scratching frequency in skin lesions were observed. The levels of immunoglobulin E (IgE), interleukin (IL)-4, IL-31, and IL-13 in serum were detected, as well as the levels of tumor necrosis factor-α (TNF-α), TRPV1, and nuclear factor (NF)-κB p65 in skin lesions in each group. Experiment 2: the optimal dose of BCG-PSN in Experiment 1 was adopted. A total of 20 KM mice were randomized into blank control, model, BCG-PSN, and BCG-PSN + PAC (PAC-14028) groups. The symptom score and scratching frequency in skin lesions were observed. The levels of IgE, IL-4, IL-31, and IL-13 in serum were detected, as well as the levels of TNF-α and TRPV1 in skin lesions in each group.
RESULTS
In Experiment 1, compared with the blank control group, the ear tissues of mice in model groups developed AD, with increased symptom score, scratching frequency, levels of IgE, IL-4, IL-31, and IL-13 in serum and levels of TNF-α, TRPV1, and NF-κB p65 in skin lesions. Compared with the model group, BCG-PSN low-dose, BCG-PSN medium-dose, BCG-PSN high-dose, and positive drug control groups had reduced AD symptoms, decreased symptom score, and decreased scratching frequency, with declined expression of each inflammatory substance, including the greatest decrease in the medium-dose group. In Experiment 2, after BCG-PSN was combined with PAC, the inflammation indexes decreased compared with those in the model group, and increased compared with those in the BCG-PSN group.
CONCLUSIONS
Intramuscular BCG-PSN can target the TRPV1 pathway, inhibit inflammation, and improve the symptoms of AD mice.
PubMed: 35722408
DOI: 10.21037/atm-22-2101 -
Frontiers in Pharmacology 2023Atopic dermatitis (AD) is an inflammatory, heterogeneous, chronic skin disorder characterized by recurrent eczematous lesions and intense pruritus, and the...
Atopic dermatitis (AD) is an inflammatory, heterogeneous, chronic skin disorder characterized by recurrent eczematous lesions and intense pruritus, and the pathophysiology mechanism of AD is known for immune dysregulation and inflammatory responses. Wuguchong (maggot) has been widely used in the wound field and found with pharmacological properties of the anti-inflammatory and immunomodulatory function. Recently, some polysaccharides were proven to have beneficial effects on AD skin lesions in mice and humans. However, the effect of the polysaccharide extracted from Wuguchong (PEW) on AD remains to be investigated. In the present study, we examined the anti-inflammatory and immunomodulatory effects of PEW on AD and explored the potential mechanisms. Balb/c mice were orally administrated with PEW to evaluate the therapeutic effect of PEW on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral PEW administration significantly ameliorated the lesions and symptoms in AD mice, such as the ear thickness and ear swelling degree, epidermal and dermal thickness, and the infiltration of mast cells. In addition, PEW treatment decreased the levels of serum IgE and histamine, the frequencies of Th1 and Th17 cells, as well as the mRNA expression levels of Th1 and Th17 cytokines and nuclear transcript factors (IFN-γ, T-bet, IL-17A, and ROR-rt). Furthermore, the activation of the NF-κB pathway and the phosphorylation of MAPKs (p38, ERK, and JNK) were significantly suppressed by PEW treatment. Taken together, our study suggests that PEW exerts anti-inflammatory and immunomodulatory effects through inhibition of Th1 and Th17 responses and downregulation of NF-κB and MAPK pathways, PEW would be developed as a promising immune therapy for AD.
PubMed: 37033625
DOI: 10.3389/fphar.2023.1119103 -
Nutrients Dec 2017has been used for food substances, as well as in herbal medicines for allergic diseases such as asthma. This study aimed to investigate the anti-atopic dermatitis (AD)...
has been used for food substances, as well as in herbal medicines for allergic diseases such as asthma. This study aimed to investigate the anti-atopic dermatitis (AD) effects of the total extract of rhizomes and active fractionson murine oxazolone- and 2,4-dinitrochlorobenzene-induced models of AD. Specific AD symptoms, such as erythema, ear swelling, and epidermis thickening, were significantly reduced in the oxazolone-mediated AD BALB/c mice upon topical application of rhizomes 95% EtOH extract (DQ). DQEA ( rhizomes EtOAc fraction) was beneficial for protecting the skin barrier against AD in DNCB-sensitized SKH-1 hairless mice. Decreased total serum IgE and IL-4 levels could be observed in atopic dorsal skin samples of the DQEA-treated group. On the basis of the phytochemical analysis, DQEA was found to contain dioscin and gracillin as its main compounds. Therapeutic applications with might be useful in the treatment of AD and related inflammatory skin diseases.
Topics: Animals; Cell Line; Dermatitis, Atopic; Dinitrochlorobenzene; Dioscorea; Female; Gene Expression Regulation; Immunoglobulin E; Interleukin-4; Mice; Mice, Hairless; Mice, Inbred BALB C; Oxazolone; Phytotherapy; Plant Extracts; RNA, Messenger; Rats; Rhizome
PubMed: 29206209
DOI: 10.3390/nu9121324 -
Biomolecules Oct 2021Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial...
Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial exposure. Although melatonin has an excellent biosafety profile and a potential to treat AD, there is limited clinical evidence from controlled trials that support the use of melatonin as an AD treatment. The delivery of melatonin via the transdermal delivery system is also a challenge in designing melatonin-based AD treatments. In this study, we generated melatonin-loaded extracellular vesicle-mimetic nanoparticles (NVs) to improve the transdermal delivery of melatonin and to evaluate their therapeutic potential in AD. The NVs were spherical nanoparticles with an average size of 100 nm, which is the optimal size for the transdermal delivery of drugs. NVs showed anti-inflammatory effects by suppressing the release of TNF-α and β-hexosaminidase in LPS-treated RAW264.7 cells and compound 48/80-treated RBL-2H3 cells, respectively. NVs showed a superior suppressive effect compared to an equivalent concentration of free melatonin. Treating a 2,4-dinitrofluorobenzene (DNCB)-induced AD-like mouse model with NVs improved AD by suppressing local inflammation, mast cell infiltration, and fibrosis. In addition, NVs effectively suppressed serum IgE levels and regulated serum IFN-γ and IL-4 levels. Taken together, these results suggest that NVs are novel and efficient transdermal delivery systems of melatonin and that NVs can be used as a treatment to improve AD.
Topics: Administration, Topical; Animals; Biomimetics; Dermatitis, Atopic; Dinitrochlorobenzene; Extracellular Vesicles; HEK293 Cells; Humans; Melatonin; Mice; Nanoparticles; RAW 264.7 Cells
PubMed: 34680082
DOI: 10.3390/biom11101450 -
Nutrients Oct 2022The genus has been traditionally used as a purgative, diuretic, stimulant, and psoriasis treatment. In this study, the anti-AD (atopic dermatitis) activities of the...
The genus has been traditionally used as a purgative, diuretic, stimulant, and psoriasis treatment. In this study, the anti-AD (atopic dermatitis) activities of the EtOH extract (DCE) were investigated in an oxazolone (OX)-induced mouse model of AD, and the anti-inflammatory effects of its active compounds were confirmed in PI-sensitized or IgE/DNP-BSA-sensitized RBL-2H3 cells. DCE improved the symptoms of OX-induced inflammatory dermatitis (swelling, erythema, and increased ear thickening) in OX-induced BALB/c mice ears and reduced epidermal thickness and mast cell infiltration. Eleven flavonoid compounds were isolated from DCE, and two compounds (7,8-dimethoxyflavone and 7,2'-dimethoxyflavone) significantly inhibited IL-4 overexpression in PI-induced RBL-2H3 cells and mast cell degranulation in IgE + DNP-BSA-induced RBL-2H3 cells. Our study indicates that DCE and two compounds (7,8-dimethoxyflavone and 7,2'-dimethoxyflavone) might effectively improve inflammatory and atopic skin symptoms.
Topics: Mice; Animals; Dermatitis, Atopic; Oxazolone; Mice, Inbred BALB C; Dinitrochlorobenzene; Thymelaeaceae; Plant Extracts; Immunoglobulin E; Mast Cells; Cytokines; Skin
PubMed: 36364783
DOI: 10.3390/nu14214521 -
Journal of Traditional Chinese Medicine... Oct 2023To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor...
Zhenxin Anshen formula ameliorates atopic der-matitis-like skin dysfunction in mice and regulation of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 in Neural pathways.
OBJECTIVE
To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) signalling pathway in mice and .
METHODS
AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. BALB/c mice were divided into five groups: normal control, model control, cetirizine, low-, medium-, and high-dose of ZXAS. After ZXAS in-tervention, the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines. Immun-oglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) were de-tected by Enzyme-linked immunosorbent assay (ELISA). The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor (GRPR), TRPV1, and TRPA1 by using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, ELISA, and Western blotting were conducted for analysis of primary dorsal root ganglia (DRG) neurons .
RESULTS
ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score, number of scratching and epidermal thickness, accompanied by the de-creased IgE and Th2 inflammatory cytokines. ZXAS also supressed the mRNA and protein expression of GRPR, TRPV1, and TRPA1 in the spinal cord. The medicated sera of ZXAS decreased capsaicin-induced Ca influx and downregulated the expression of TRPV1, TRPA1, and phospholipase C in DRG neurons.
CONCLUSIONS
The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca2+ signals in neurons.
Topics: Animals; Mice; Ankyrins; Dinitrochlorobenzene; Antineoplastic Agents; Dermatitis, Atopic; Cytokines; Neural Pathways; Dinitrobenzenes; Immunoglobulin E
PubMed: 37679976
DOI: 10.19852/j.cnki.jtcm.20230802.003 -
Scientific Reports May 2020The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress...
The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl-Pro-His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.
Topics: Amides; Animals; Antioxidants; Caffeic Acids; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Eosinophils; Female; Filaggrin Proteins; Heme Oxygenase-1; Immunoglobulin E; Interleukins; Intermediate Filament Proteins; Mast Cells; Membrane Proteins; Mice; Mice, Inbred BALB C; Protein Precursors; Pruritus; Skin; Tight Junctions; Thymic Stromal Lymphopoietin
PubMed: 32439906
DOI: 10.1038/s41598-020-65502-2