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International Journal of Molecular... Nov 2021Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the family, and is well known for its beneficial pharmacological activities....
Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.
Topics: Animals; Cell Line; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Humans; In Vitro Techniques; Inflammation; Irritants; Keratinocytes; Mice; Mice, Inbred ICR; NF-kappa B; Oleanolic Acid; Signal Transduction
PubMed: 34769428
DOI: 10.3390/ijms222112000 -
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 -
The Journal of Investigative Dermatology Apr 1976Evidence in favor of a role for Langerhans cells in contact allergic hypersensitivity reactions has been reviewed. This includes mononuclear cell to Langerhans cell... (Comparative Study)
Comparative Study Review
Evidence in favor of a role for Langerhans cells in contact allergic hypersensitivity reactions has been reviewed. This includes mononuclear cell to Langerhans cell apposition and damage to some Langerhans cells at sites of specific challenge to a variety of contact allergens. Such apposition occurs in actively sensitized patients and guinea pigs and in passively sensitized guinea pigs. In addition, in passively sensitized guinea pigs Langerhans cells circulate in dermal vessels resembling lymphatics and are much increased in the dermis after challenge with the contact allergen. These observations, together with the existing knowledge that Langerhans cells occur in the lymph nodes and thymus, suggest that these cells may be involved not only in contact allergic reactions but also in other immunologic reactions, particularly in cell-mediated reactions in the skin.
Topics: Animals; Dermatitis, Contact; Dinitrochlorobenzene; Guinea Pigs; Humans; Immunity, Cellular; Langerhans Cells; Skin
PubMed: 774995
DOI: 10.1111/1523-1747.ep12482139 -
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 -
Molecules (Basel, Switzerland) Sep 2021S. Moore is a perennial herbaceous plant classified as Asteraceae of the genus Artemisia. Many species of have been used as medicinal materials. S. Moore has been...
Herba Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and the Production of Pro-Inflammatory Mediators in Tumor Necrosis Factor Alpha-/Interferon Gamma-Induced HaCaT Cells.
S. Moore is a perennial herbaceous plant classified as Asteraceae of the genus Artemisia. Many species of have been used as medicinal materials. S. Moore has been widely used in China to treat inflammatory diseases. However, the mechanism of its action on the keratinocyte inflammatory response is poorly understood. Here, we investigated the anti-inflammatory reaction of S. Moore ethanol extract (EAA) using human keratinocyte (HaCaT) cells, which involved investigating the nuclear factor kappa B (NF-κB), signal transducer, and activator of transcription-1 (STAT-1), as well as mitogen-activated protein kinase (MAPK) signaling pathways and atopic dermatitis-like skin lesions in mice. We elucidated the anti-inflammatory effects of EAA on tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated human keratinocyte cells and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice. The levels of chemokines and cytokines (IL-8, IL-6, TARC, and RANTES) were determined by an enzyme-linked immunosorbent assay. The NF-κB, STAT-1, and MAPK signaling pathways in HaCaT cells were analyzed by western blotting. Thickening of the mice dorsal and ear skin was measured and inflammatory cell infiltration was observed by hematoxylin and eosin staining. Results showed that EAA suppressed IL-8, IL-6, TARC, and RANTES production. EAA inhibited nuclear translocation of NFκB and STAT-1, as well as reduced the levels of phosphorylated ERK MAPKs. EAA improved AD-like skin lesions in DNCB-treated mice. These findings suggest that EAA possesses stronger anti-inflammatory properties and can be useful as a functional food or candidate agent for AD.
Topics: Animals; Anti-Inflammatory Agents; Artemisia; Chemokines; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; HaCaT Cells; Humans; Inflammation Mediators; Interferon-gamma; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases; Plant Extracts; STAT1 Transcription Factor; Signal Transduction; Skin; Tumor Necrosis Factor-alpha
PubMed: 34500860
DOI: 10.3390/molecules26175427 -
Annals of Surgery Sep 1975Host resistance to infection was measured by the in vivo response to 5 delayed hypersensitivity antigens and to sensitivity and challenge by dinitrochlorobenzene (DNCB)...
Host resistance to infection was measured by the in vivo response to 5 delayed hypersensitivity antigens and to sensitivity and challenge by dinitrochlorobenzene (DNCB) in 55 seriously ill or injured patients and in 50 preoperative patients. A close correlation between infections, septicemia, death related to infection and anergy was found in the postoperative and post injury patients and was predictive of these complications in the patients studied preoperatively. Decreased body cell mass was noted in both the anergic and non-anergic patients which was consistent with protein-calorie malnutrition but the two groups were not significantly different. A serum factor which inhibited cellular immunity in vitro was found in 4 patients. This factor disappeared in the two patients who recovered. The study suggests the therapeutic value of the in vivo measurement of delayed hypersensitivity in seriously ill and especially preoperative patients in whom specific or non-specific stimulation of cell mediated immunity might alter the risk of infection.
Topics: Adolescent; Adult; Aged; Bacterial Infections; Blood Protein Electrophoresis; Body Composition; Dinitrochlorobenzene; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunoelectrophoresis; Lectins; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Neutrophils; Postoperative Complications; Potassium; Protein-Energy Malnutrition; Risk; Sepsis; Skin Tests; Sodium; Surgical Procedures, Operative; Surgical Wound Infection; T-Lymphocytes; Wounds and Injuries
PubMed: 126046
DOI: 10.1097/00000658-197509000-00004 -
Nutrients Aug 2020The present study investigated the protective effects of () ethanol extract (SHE) against atopic dermatitis (AD), known as an abnormal immune response in house dust...
The present study investigated the protective effects of () ethanol extract (SHE) against atopic dermatitis (AD), known as an abnormal immune response in house dust mite (HDM)/2,4-dinitrochlorobenzene (DNCB)-stimulated NC/Nga mice. The oral administration of SHE attenuated the AD symptoms, including the skin dermatitis severity, transepidermal water loss (TEWL), and ear edema in HDM/DNCB-stimulated mice. Moreover, the histological analysis revealed that SHE improved epidermal hyperplasia and hyperkeratosis, and reduced the dermal infiltrations of mast cells and eosinophils. Moreover, SHE downregulated the expression levels of cytokines (interleukin (IL)-6, IL-10, and interferon (IFN)-γ) and chemokines (Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), Eotaxin, and Thymus and activation-regulated chemokine (TARC)) by decreasing the expression levels of atopic initiators (IL-25 and IL-33) in HDM/DNCB-stimulated skin. The oral administration of SHE decreased the spleen size, reducing expression levels of AD-related cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IFN-γ, and TARC) by regulating the expressions of Tbx21 (T-bet), GATA Binding Protein 3 (GATA-3), and Signal transducer and activator of transcription 3 (STAT3). Moreover, SHE significantly attenuated the serum immunoglobulin (Ig)G and IgG levels in HDM/DNCB-stimulated mice. Collectively, these results suggest that could be an ingredient of functional food against abnormal immune response.
Topics: Administration, Oral; Animals; Chemokines; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Functional Food; GABA Plasma Membrane Transport Proteins; Gene Expression; Immunoglobulin G; Mice; Plant Extracts; Pyroglyphidae; STAT3 Transcription Factor; Sargassum; Severity of Illness Index
PubMed: 32824648
DOI: 10.3390/nu12082482