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BMC Complementary Medicine and Therapies Mar 2021Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox...
BACKGROUND
Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice.
METHODS
Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate.
RESULTS
Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th and Th) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th and Th and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups.
CONCLUSION
Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.
Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Female; Humans; Immunoglobulin E; Mice; Mice, Hairless; Minerals; Nitric Oxide; Skin
PubMed: 33658026
DOI: 10.1186/s12906-021-03259-5 -
Molecules (Basel, Switzerland) Jun 2022(-)-α-Bisabolol (BIS) is a sesquiterpene alcohol derived mostly from L., which is a traditional herb and exhibits multiple biologic activities. BIS has been reported...
(-)-α-Bisabolol (BIS) is a sesquiterpene alcohol derived mostly from L., which is a traditional herb and exhibits multiple biologic activities. BIS has been reported for treatment of skin disorders, but the effect of BIS on anti-atopic dermatitis (AD) remains unclear. Therefore, we investigated the effects of BIS on 2,4-dinitrochlorobenzene (DNCB)-induced AD in BALB/c mice and the underlying mechanism in Bone Marrow-Derived Mast Cells (BMMCs). Topical BIS treatment reduced AD-like symptoms and the release of interleukin (IL)-4 without immunoglobulin (Ig)-E production in DNCB-induced BALB/c mice. Histopathological examination revealed that BIS reduced epidermal thickness and inhibited mast cells in the AD-like lesions skin. Oral administration of BIS effectively and dose-dependently suppressed mast-cell-mediated passive cutaneous anaphylaxis. In IgE-mediated BMMCs, the levels of β-hexosaminidase (β-hex), histamine, and tumor necrosis factor (TNF)-α were reduced by blocking the activation of nuclear factor-қB (NF-қB) and c-Jun N-terminal kinase (JNK) without P38 mitogen activated protein (P38) and extracellular regulated protein kinases (Erk1/2). Taken together, our experimental results indicated BIS suppresses AD by inhibiting the activation of JNK and NF-κB in mast cells. BIS may be a promising therapeutic agent for atopic dermatitis and other mast-cell-related diseases.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Mast Cells; Mice; Mice, Inbred BALB C; Monocyclic Sesquiterpenes; NF-kappa B; Skin; Tumor Necrosis Factor-alpha
PubMed: 35807237
DOI: 10.3390/molecules27133985 -
Parasites & Vectors Feb 2018Ticks are obligate hematophagous parasites important economically and to health. Ticks consume large amounts of blood for their survival and reproduction; however, large...
BACKGROUND
Ticks are obligate hematophagous parasites important economically and to health. Ticks consume large amounts of blood for their survival and reproduction; however, large amounts of iron in blood could lead to oxidative stress. Ticks use several molecules such as glutathione S-transferases (GSTs), ferritins, and peroxiredoxins to cope with oxidative stress. This study aimed to identify and characterize the GSTs of the hard tick Haemaphysalis longicornis in order to determine if they have a role in coping with oxidative stress.
METHODS
Genes encoding GSTs of H. longicornis were isolated from the midgut CDNA library. Genes have been cloned and recombinant GSTs have been expressed. The enzymatic activities, enzyme kinetic constants, and optimal pH of the recombinant GSTs toward 1-chloro-2,4-dinitrobenzene (CDNB) were determined. The gene transcription and protein expression profiles were determined in the whole ticks and internal organs, and developmental stages using real time RT-PCR and Western blotting during blood feeding. The localization of GST proteins in organs was also observed using immunofluorescent antibody test (IFAT).
RESULTS
We have isolated two genes encoding GSTs (HlGST and HlGST2). The enzymatic activity toward CDNB is 9.75 ± 3.04 units/mg protein for recombinant HlGST and 11.63 ± 4.08 units/mg protein for recombinant HlGST2. Kinetic analysis of recombinant HlGST showed K values of 0.82 ± 0.14 mM and 0.64 ± 0.32 mM for the function of CDNB and GSH, respectively. Meanwhile, recombinant HlGST2 has K values of 0.61 ± 0.20 mM and 0.53 ± 0.02 mM for the function of CDNB and GSH, respectively. The optimum pH of recombinant HlGST and recombinant HlGST2 activity was 7.5-8.0. Transcription of both GSTs increases in different developmental stages and organs during blood-feeding. GST proteins are upregulated during blood-feeding but decreased upon engorgement in whole ticks and in some organs, such as the midgut and hemocytes. Interestingly, salivary glands, ovaries, and fat bodies showed decreasing protein expression during blood-feeding to engorgement. Varying localization of GSTs in the midgut, salivary glands, fat bodies, ovaries, and hemocytes was observed depending on the feeding state, especially in the midgut and salivary glands.
CONCLUSIONS
In summary, a novel GST of H. longicornis has been identified. Characterization of the GSTs showed that GSTs have positive correlation with the degree and localization of oxidative stress during blood-feeding. This could indicate their protective role during oxidative stress.
Topics: Animal Structures; Animals; Blotting, Western; Dinitrochlorobenzene; Enzyme Stability; Feeding Behavior; Fluorescent Antibody Technique, Direct; Gene Expression Profiling; Glutathione Transferase; Hydrogen-Ion Concentration; Ixodidae; Kinetics; Oxidative Stress; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Stress, Physiological
PubMed: 29422079
DOI: 10.1186/s13071-018-2667-1 -
Frontiers in Pharmacology 2018Atopic dermatitis (AD) is a chronic inflammatory skin disease. Bleomycin (BLM) contributes to the induction of pulmonary inflammation and fibrosis in animals. Although...
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Bleomycin (BLM) contributes to the induction of pulmonary inflammation and fibrosis in animals. Although skin and lung tissue inflammation is closely related in the pathogenesis of allergic diseases, a proper animal model for investigating the relationship between skin and lung inflammation is lacking. Therefore, we developed a mouse model of AD with relapsing dermatitis and pulmonary fibrosis caused by the administration of allergen and BLM. The present study determined whether lung injury caused by the bronchial application of BLM would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. NC/Nga mice treated with BLM and DNCB had increased severity of clinical symptoms and airway hyperresponsiveness as well as increased inflammatory cell infiltration and collagen deposition in the dorsal skin and lung. Compared to normal mice, interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in bronchoalveolar lavage fluid were increased in NC/Nga mice treated with both DNCB and BLM and in animals treated with DNCB alone. Administration of BLM and DNCB increased the levels of IL-4 and IL-13 production in spleen cells and eotaxin-2 mRNA expression in dorsal skin, compared to NC/Nga mice treated with DNCB alone. The total cell numbers in axillary lymph node, bronchoalveolar lavage, and thymus were increased in DNCB-BLM mice compared to those in mice treated with DNCB alone. Administration of BLM and DNCB increased the numbers of cluster of differentiation 4 (CD4)+ T cells and CD11b+granulocyte-differentiation antigen-1 (Gr-1)+ cells among peripheral blood mononuclear cells, CD4+ cells in bronchoalveolar lavage, CD4+ and B220+CD23+ B cells in the axillary lymph node, and CD4+ cells in thymus, compared to DNCB-treated mice. The number of total, CD4+, and CD11b+Gr-1+ cells in the lung were increased in both DNCB and DNCB-BLM mice. These results demonstrate that BLM aggravates allergic skin inflammation and promotes airway hyperreactivity and lung inflammation when combined with DNCB in NC/Nga mice.
PubMed: 29910732
DOI: 10.3389/fphar.2018.00578 -
Molecular Medicine Reports Oct 2020The present study aimed to investigate the effects of Solanum nigrum Linne (SNL) in a model of 1‑chloro‑2,4‑dinitrobenzene (DNCB)‑induced atopic dermatitis (AD)...
The present study aimed to investigate the effects of Solanum nigrum Linne (SNL) in a model of 1‑chloro‑2,4‑dinitrobenzene (DNCB)‑induced atopic dermatitis (AD) and in TNF‑α/IFN‑γ‑stimulated HaCaT cells. AD is a chronic inflammatory skin disease and is characterized by erythema, edema, increased pruritus and eczema. Steroids are most commonly used for anti‑inflammatory therapy; however, their long‑term use is limited due to side‑effects, such as osteoporosis, brittle skin, muscle weaknesses and diabetes. Therefore, patients with AD require alternative treatment strategies. In previous studies, SNL has been reported to be effective against oxidants and cancer. However, to the best of our knowledge, the effects of SNL on AD have not yet been investigated. The present study examined the effects of SNL ethanol extract on a model of DNCB induced AD and on TNF‑α/IFN‑γ‑stimulated HaCaT cells. The skin tissue was sectioned to measure the thicknesses of the epidermis and dermis, as well as the numbers of eosinophils, mast cells and CD8 infiltration by H&E, toluidine blue, Masson's trichrome and IHC staining. ELISA was performed using serum to measure IgE levels. The present study also examined the expression of various inflammatory cytokines, MAPK and NF‑κB in TNF‑α/IFN‑γ‑stimulated HaCaT cells. SNL significantly reduced the levels of cytokines released from HaCaT cells stimulated with TNF‑α/IFN‑γ. SNL also significantly reduced the levels of p‑p38 at 30 min and significantly reduced the activation of NF‑κB in a time course experiment. In addition, SNL significantly reduced the level of serum IgE and dermal thickness and the infiltration of mast cells and CD8 in the BALB/c mouse model of DNCB‑induced AD. The results of the current study suggest that SNL exerts a suppressive effect on pro‑inflammatory cytokines in vitro and in vivo through the regulation of the immune system.
Topics: Animals; Anti-Inflammatory Agents; Cell Survival; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; HaCaT Cells; Humans; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Phytotherapy; Plant Extracts; Signal Transduction; Skin; Solanum nigrum; Treatment Outcome
PubMed: 32945415
DOI: 10.3892/mmr.2020.11381 -
Molecules (Basel, Switzerland) Apr 2021Human glutathione transferase A1-1 (hGSTA1-1) contributes to developing resistance to anticancer drugs and, therefore, is promising in terms of drug-design targets for...
Human glutathione transferase A1-1 (hGSTA1-1) contributes to developing resistance to anticancer drugs and, therefore, is promising in terms of drug-design targets for coping with this phenomenon. In the present study, the interaction of anthraquinone and diazo dichlorotriazine dyes (DCTD) with hGSTA1-1 was investigated. The anthraquinone dye Procion blue MX-R (PBMX-R) appeared to interact with higher affinity and was selected for further study. The enzyme was specifically and irreversibly inactivated by PBMX-R, following a biphasic pseudo-first-order saturation kinetics, with approximately 1 mol of inhibitor per mol of the dimeric enzyme being incorporated. Molecular modeling and protein chemistry data suggested that the modified residue is the Cys112, which is located at the entrance of the solvent channel at the subunits interface. The results suggest that negative cooperativity exists upon PBMX-R binding, indicating a structural communication between the two subunits. Kinetic inhibition analysis showed that the dye is a competitive inhibitor towards glutathione (GSH) and mixed-type inhibitor towards 1-chloro-2,4-dinitrobenzene (CDNB). The present study results suggest that PBMX-R is a useful probe suitable for assessing by kinetic means the drugability of the enzyme in future drug-design efforts.
Topics: Amino Acid Sequence; Anticarcinogenic Agents; Binding Sites; Coloring Agents; Dinitrochlorobenzene; Glutathione; Glutathione Transferase; Humans; Kinetics; Neoplasms; Protein Binding; Triazines
PubMed: 33924269
DOI: 10.3390/molecules26082399 -
Nutrients Sep 2021The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries....
The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.
Topics: Animals; Benzofurans; Cytokines; Depsides; Dermatitis, Atopic; Gene Expression Regulation; Immunoglobulin G; Lithospermum; Male; Mice; Mice, Inbred Strains; Plant Extracts; Skin; Spleen; Th1-Th2 Balance
PubMed: 34579088
DOI: 10.3390/nu13093209 -
Wounds : a Compendium of Clinical... Nov 2019Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in children worldwide. Resveratrol exerts various pharmacologic effects, and...
INTRODUCTION
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in children worldwide. Resveratrol exerts various pharmacologic effects, and application of resveratrol has been suggested as an alternative treatment for microorganism infection and skin pathologies.
OBJECTIVE
The present study examines the effect of resveratrol on AD using an in vivo murine model.
MATERIALS AND METHODS
Atopic dermatitis was induced in 30 BALB/c mice by topical application of 2,4-dinitrochlorobenzene (DNCB) prior to treatment with 0 mg/kg, 5 mg/kg, or 25 mg/kg resveratrol. Histologic data changes were evaluated, and the levels of thymus- and activation-regulated chemokine; type 2 helper T cytokines interleukin (IL) 4, IL-5, and IL-13; and type 1 helper T cytokines IL-12 and interferon γ were examined by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression was evaluated with quantitative polymerase chain reaction. Filaggrin (FLG), envoplakin (EVPL), transglutaminase (TG), and kallikrein 7 (KLK7) protein expression were evaluated with Western blot.
RESULTS
Resveratrol ameliorated the onset of AD-like skin lesions and significantly improved the DNCB-induced dermal destruction in mice. In addition, resveratrol reduced the levels of the above chemokines, downregulated the expression of the proinflammatory cytokine KLK7, and upregulated the expression of several cytokines, such as EVPL, FLG, and TG.
CONCLUSIONS
These results suggest resveratrol has therapeutic effects in the treatment of AD.
Topics: Animals; Antioxidants; CD4-Positive T-Lymphocytes; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Male; Mice; Mice, Inbred BALB C; Resveratrol; Skin
PubMed: 31730508
DOI: No ID Found -
Insects Mar 2022Odorant-degrading enzymes (ODEs) play an important role in rapidly degrading and inactivating odorant molecules that have completed information transmission, as well as...
Odorant-degrading enzymes (ODEs) play an important role in rapidly degrading and inactivating odorant molecules that have completed information transmission, as well as in maintaining the stability and sensitivity of insect olfactory sensing systems. Glutathione S-transferases (GSTs), as a group of ODEs, supposedly bear the ability to catalyze the conjugation of glutathione (GSH) and xenobiotic odorant molecules in the degrading process. However, there are few reports regarding the role of the GST genes of in the degrading process. Thus, we characterized 13 full-length genes encoding GST sequences from , of which only contained a high abundance in the antennae. Ligand-binding assays implied that SzeaGSTd1 was able to catalyze the conjugation of GSH with 2, 4-dinitrochlorobenzene (CDNB). We investigated whether recombinant SzeaGSTd1 bears the ability to degrade the volatile molecules of the host; among the host volatiles, and found capryl alcohol to be a suitable substrate for SzeaGSTd1. These results strongly suggest that SzeaGSTd1 probably plays a role in auxiliary host location by degrading the host volatiles of capryl alcohol and exhibits a potential biological function in the olfactory sensing system of . Knowledge of the potential functions of SzeaGSTd1 will provide new ideas for biological control strategies for .
PubMed: 35323557
DOI: 10.3390/insects13030259 -
Evidence-based Complementary and... 2021Prevalence of atopic dermatitis (AD), a chronic, pruritic, and relapsing inflammatory skin disorder, is growing. Because available therapeutics is limited, immune...
Prevalence of atopic dermatitis (AD), a chronic, pruritic, and relapsing inflammatory skin disorder, is growing. Because available therapeutics is limited, immune regulators from natural resources could be helpful for treating AD symptoms. The root of Bunge (Lamiaceae) has been studied for the treatment of inflammatory diseases, including dermatologic disorders in Korea. This study examined the effect of salvianolic acid A on AD-like symptoms. Sensitization on the dorsal skin and repeated application on the ears with 2,4-dinitrochlorobenzene (DNCB) were performed in BALB/c mice to induce AD-like skin lesions. After induction of atopic dermatitis, salvianolic acid A (5 and 10 mg/kg) or dexamethasone (10 mg/kg) were administrated via intraperitoneal injection for 3 weeks. Salvianolic acid A suppressed DNCB-induced AD-like symptoms like ear skin hypertrophy and decreased mast cell infiltration into skin lesions. Salvianolic acid A not only reduced DNCB-induced increase of serum IgE but also lowered levels of the Th2 cytokines (IL-4 and IL-13), Th1 cytokine (interferon-), and Th17 cytokine (IL-17A). Furthermore, salvianolic acid A blocked DNCB-induced lymph node enlargement. In summary, these results suggest that salvianolic acid A might have a therapeutic potential for the treatment of AD.
PubMed: 34691223
DOI: 10.1155/2021/7902592