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Frontiers in Pharmacology 2021Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory,...
Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory, and antidepressant activities of pumpkin were previously reported. This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit ( L.) extract (PE) in relieving CD associated with chronic stress-induced depression and compare it to the topical pumpkin extract alone and to the standard treatment. Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups ( = 10 each); untreated, betamethasone-treated, PE-treated and pumpkin extract cream, and oral-treated groups. Treatments were continued for 2 weeks. All groups were compared to the negative control group ( = 10). Depression was behaviorally and biochemically confirmed. Serum and mRNA levels of pro-inflammatory cytokines, such as TNF-α, IL-6, COX-2, and iNOS, were assessed. Oxidant/antioxidant profile was assessed in the serum and skin. Histopathological and immunohistochemical assessments of affected skin samples were performed. Pumpkin extract, used in this study, included a large amount of oleic acid (about 56%). The combined topical and oral administration of PE significantly reduced inflammatory and oxidative changes induced by CD and depression compared to the CD standard treatment and to the topical PE alone. PE significantly alleviated CD signs and the histopathological score ( < 0.001) mostly through the downregulation of pro-inflammatory cytokines and the upregulation of antioxidants. Pumpkin extract, applied topically and orally, could be an alternative and/or complementary approach for treating contact dermatitis associated with depression. Further studies on volunteer patients of contact dermatitis are recommended.
PubMed: 34040528
DOI: 10.3389/fphar.2021.663417 -
Journal of Immunology (Baltimore, Md. :... Feb 2022Calcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17...
Calcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4 T cells from draining lymph nodes showed significantly reduced IL-17A expression with significantly increased IFN-γ, IL-4, and IL-22 expression at the protein and mRNA levels compared with control mice. Retinoic acid receptor-related orphan receptor γ t mRNA was significantly reduced, while mRNAs for T-box expressed in T cells and GATA binding protein 3 were significantly increased. In addition, EC RAMP1 knockout mice had significantly reduced contact hypersensitivity responses, and systemic administration of a CGRP receptor antagonist similarly inhibited contact hypersensitivity in wild-type mice. These observations provide compelling evidence that CGRP is a key regulator of cutaneous immunity through effects on ECs and suggest a novel pathway for potential therapeutic manipulation.
Topics: Animals; Antigen Presentation; Calcitonin Gene-Related Peptide; Dermatitis, Contact; Dinitrofluorobenzene; Endothelial Cells; GATA3 Transcription Factor; Interferon-gamma; Interleukin-17; Interleukin-4; Interleukins; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 1, Group F, Member 1; Receptor Activity-Modifying Protein 1; Skin; Th1 Cells; Th17 Cells; Th2 Cells; Interleukin-22
PubMed: 35031579
DOI: 10.4049/jimmunol.2100139 -
International Journal of Molecular... Oct 2023The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments....
The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) injection. Two different protocols were applied. In the preventive protocol, ALCAR was administered daily starting 14 days to 24 h before the delivery of DNBS. In the interventive protocol, ALCAR was daily administered starting the same day of DNBS injection, and the treatment was continued for 14 days. In both cases, ALCAR significantly reduced the establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one. The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis, as analyzed by immunofluorescence. On the other hand, the preventive protocol effectively protected enteric neurons from the inflammatory insult. These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from IBDs.
Topics: Humans; Rats; Animals; Acetylcarnitine; Visceral Pain; Hyperalgesia; Colitis; Neuroglia; Central Nervous System
PubMed: 37834289
DOI: 10.3390/ijms241914841 -
International Journal of Molecular... Aug 2023(L.) S. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this...
(L.) S. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<-8 kcal/mol) and IL-6 (<-6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-ɣ, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides.
Topics: Animals; Mice; Dinitrofluorobenzene; Interleukin-6; Luteolin; Dermatitis, Contact; Tumor Necrosis Factor-alpha; Araceae; Dinitrobenzenes; Anti-Inflammatory Agents; Plant Extracts
PubMed: 37686078
DOI: 10.3390/ijms241713271 -
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 -
Experimental Biology and Medicine... Oct 2019This study investigated the safety and effect of oxymatrine (OMT) and/or diammonium glycyrrhizinate (DG) on allergic contact dermatitis (ACD) induced by...
UNLABELLED
This study investigated the safety and effect of oxymatrine (OMT) and/or diammonium glycyrrhizinate (DG) on allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB) in ICR mice. Mice were topically smeared with vehicle (control) or DNFB on their ear and skin to induce ACD. The mice were randomized and injected with saline as the model, treated intraperitoneally with dexamethasone (DEX), 45 or 90 mg·kg OMT and/or DG daily beginning one day post the first smearing for two weeks. The body weights, the severity of ear and skin inflammation, the levels of serum IgE, IL-4, and IFNγ, creatinine and urea as well as plasma sodium and potassium in individual mice were measured. In comparison with the control group, the model group did not change the body weights, but developed severe skin and ear inflammation with increased ear thickness, accompanied by many inflammatory infiltrates in the lesions and high levels of serum IgE, IL-4, and IFNγ. Combination of OMT and DG prevented the OMT- or DG-altered body weights in mice. While treatment with either OMT or DG moderately reduced the skin and ear inflammation, their thickness and inflammatory infiltrates, combination of OMT and DG further significantly increased their anti-inflammatory effects in mice. A similar pattern of inhibitory effect on the levels of serum IgE, IL-4, and IFNγ was observed in the different groups of mice. Combination of OMT and DG also prevented the OMT-, DG-, or DEX-altered plasma sodium or potassium levels in mice. Therefore, combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in mice and attenuated DG- or OMT-related adverse effects.
IMPACT STATEMENT
Diammonium glycyrrhizinate (DG) and oxymatrine (OMT) have similar anti-inflammatory, anti-allergic, anti-tumor, immunomodulatory, and other pharmacological properties. Our previous study has shown that when DG and OMT are combined, DG can attenuate both high-dose (347.44 mg·kg) and regular-dose (90 mg·kg) OMT-induced mortality and adverse effects (such as body weight loss and hyponatremia). Furthermore, OMT can similarly attenuate the adverse effects (such as body weight gain, hypernatremia, and hypokalemia) induced by regular dose (90 mg·kg) of DG. Accordingly, we tested whether combination of OMT and DG would increase anti-inflammatory activities and reduce their adverse effect in a mouse model of allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Our findings indicated that combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in ICR mice and attenuated adverse effects of DG or OMT alone.
Topics: Alkaloids; Animals; Creatinine; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Drug Therapy, Combination; Ear; Glycyrrhizic Acid; Immunoglobulin E; Inflammation; Interferon-gamma; Interleukin-4; Male; Mice, Inbred BALB C; Mice, Inbred ICR; Potassium; Quinolizines; Skin; Sodium; Urea
PubMed: 31342769
DOI: 10.1177/1535370219864895 -
Postepy Dermatologii I Alergologii Apr 2022The link between psychological stress and skin diseases, such as atopic dermatitis is established. Pumpkin was proved to have antioxidant, anti-inflammatory and...
INTRODUCTION
The link between psychological stress and skin diseases, such as atopic dermatitis is established. Pumpkin was proved to have antioxidant, anti-inflammatory and accelerating wound healing potential.
AIM
To assess the efficacy of pumpkin fruit (.) extract (PE) in relieving contact dermatitis (CD) in depressed rats compared to a standard treatment of CD and explore the mechanism behind this effect.
MATERIAL AND METHODS
Thirty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression, then exposed to 1-fluoro-2,4-dinitrofluorobenzene (DNFB) for 2 weeks for induction of CD. The rats were then divided into 3 groups ( = 10 each); the positive control, Betamethasone-treated, and PE-treated groups. Depression was confirmed by the forced swim test and measuring the serum corticosterone level. Proinflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were measured in the skin and serum and their mRNA levels were assessed using qRT-PCR. Oxidant/antioxidant profile including levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) was assessed in the skin and serum. Histopathological assessment of skin samples was performed and CD4 and CD68 immunoexpression was assessed.
RESULTS
The used PE included a large amount of oleic acid (about 56%) and a small amount of linoleic acid (about 1%). The topical application of PE significantly attenuated inflammation and oxidative changes attributed to CD associated with chronic stress-induced depression comparable to the standard treatment of CD. PE significantly alleviated signs and histopathological score of CD ( < 0.001) through the significant down-regulation of pro-inflammatory cytokines and the significant up-regulation of antioxidants in the skin. Significant down-regulation ( < 0.001) of TNF-α, IL-6, COX-2 and iNOS gene expression in the PE-treated group confirmed the anti-inflammatory action of PE.
CONCLUSIONS
The pumpkin extract, applied topically in CD associated with depression, could be an alternative as well as preventive approach in treating CD. Anti-inflammatory and antioxidants activity of pumpkin is a proposed mechanism behind this effect. Further studies to test this effect on volunteer patients of CD are recommended.
PubMed: 35645683
DOI: 10.5114/ada.2021.103459 -
Computational and Mathematical Methods... 2022Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life,...
BACKGROUND
Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life, underscoring the need for the development of safe and effective therapeutic agents to treat affected individuals. Fisetin is a Chinese herbal preparation that reportedly exhibits antitumor, antioxidant, antimicrobial, anticoagulatory, and antimalarial activity. In the current report, the immunomodulatory activity of fisetin was appraised by assessing its impact on balance between regulatory T (Treg) and Th17 cells in an ACD model.
METHODS
BALB/c mice ( = 60) were randomized into control, ACD model, CTX positive control (20 mg/kg), and fisetin treatment groups (three dose levels: 2, 4, or 8 mg/kg). ACD induction was achieved by sensitizing mice on the shaved ventral abdomen via the application of 5% DNFB (50 L) on days 1 and 2, followed by rechallenge in the right ear with 5% DNFB (20 L) on day 5. Beginning on day 1, immunized mice were intraperitoneally injected with the appropriate fisetin dose (in saline) once per day for 7 days. On day 7, ear swelling, transcription factor expression, Th17/Treg cell populations, and cytokine production were assessed in vivo.
RESULTS
Fisetin treatment significantly suppressed ear swelling and associated inflammatory cell infiltration, besides reducing the production of Th17 cytokines (IL-17, TNF-, and IL-6) and the expression of the Th17 lineage transcription factor RORt while simultaneously enhancing Treg-specific cytokine production (TGF- and IL-10) and the expression of the Treg lineage transcription factor Foxp3, thereby restoring the Th17/Treg cell in ACD mice.
CONCLUSIONS
These data indicate that fisetin exhibits immunomodulatory activity and can alter the Th17/Treg cell balance, highlighting its potential value as a treatment drug for ACD.
Topics: Animals; Cytokines; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Flavonols; Humans; Mice; Mice, Inbred BALB C; Quality of Life; T-Lymphocytes, Regulatory; Th17 Cells; Transcription Factors
PubMed: 35437448
DOI: 10.1155/2022/9222541 -
The Journal of Investigative Dermatology Nov 2015Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally....
Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally. In NC/Nga mice, repetitive applications of 2, 4-dinitrofluorobenzene (DNFB) evoke AD-like clinical symptoms similar to human AD. Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is a methyl ester of a dipeptide, which is used as an artificial non-nutritive sweetener. Aspartame has analgesic and anti-inflammatory functions that are similar to the function of nonsteroidal anti-inflammatory drugs such as aspirin. We investigated whether aspartame can relieve AD-like clinical symptoms induced by DNFB treatment in NC/Nga mice. Sucrose did not relieve AD-like symptoms, whereas aspartame at doses of 0.5 μg kg(-1) and 0.5 mg kg(-1) inhibited ear swelling and relieved AD-like clinical symptoms. Aspartame inhibited infiltration of inflammatory cells including eosinophils, mast cells, and CD4(+) T cells, and suppressed the expression of cytokines including IL-4 and IFN-γ, and total serum IgE levels. Aspartame may have therapeutic value in the treatment of AD.
Topics: Analysis of Variance; Animals; Aspartame; Biopsy, Needle; Cytokines; Dermatitis, Atopic; Dinitrofluorobenzene; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Flavanones; Humans; Immunoglobulin E; Immunohistochemistry; Male; Mice; Random Allocation
PubMed: 26099025
DOI: 10.1038/jid.2015.234 -
Scientific Reports Jul 2018Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for...
Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes. The MSC sheets were endoscopically transplanted to the inflamed area in electrocoagulation and DNBS colitis model. The effect of the transplantation was verified using endoscopic scoring and histological analysis. In the electrocoagulation model, the AD-MSC group showed significantly decreased ulcer size in the transplanted regions. In the DNBS colitis model, the AD-MSC group showed decreased inflammation and colitis in the transplanted regions. Histologic analysis showed that the MSC sheets had successfully attached to the inflamed mucosa in both the electrocoagulation and DNBS colitis model. Our results show that endoscopic transplantation of MSC sheets could be a new effective mode of stem cell therapy for IBD treatment.
Topics: Animals; Colitis; Dinitrofluorobenzene; Disease Models, Animal; Endoscopes; Green Fluorescent Proteins; Humans; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Rats; Rats, Transgenic
PubMed: 30054522
DOI: 10.1038/s41598-018-29617-x