ABSTRACT
Dendritic cells (DCs) are play critical roles in the priming and regulation of immune responses. DCs rapidly process and convey these antigens to prime antigen-specific T cells. Therefore, regulation of DCs functions is important for immunity and immunotherapies. Immune adjuvants for DCs activation are needed to improve the efficacy of vaccines against tumors and many infectious diseases. Therefore, we demonstrate that H. fusiformis extract can regulate DCs maturation and activation. H. fusiformis extract induced costimulatory molecules (CD 80 and CD86), antigen-presenting molecules (major histocompatibility complex (MHC) I and II), CCR7 expression, and interleukin (IL)-12 production in DCs. These effects are associated with upregulation of mitogen-activated protein kinase (MAPK) signaling pathway. In addition, H. fusiformis extract induces costimulatory molecules on splenic DCs and activated CD8+ T cells in vivo. Taken together, these findings suggest that H. fusiformis extract may be a potential efficient immune therapeutic compound in DCs-mediated immunotherapies. ABBREVIATIONS: CTL: cytotoxic T lymphocytes; DCs: dendritic cells; ERK: extracellular signal-regulated kinases; IL: interleukini; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MHC: major histocompatibility complex.
Subject(s)
Dendritic Cells/cytology , Dendritic Cells/drug effects , Plant Extracts/pharmacology , Sargassum/chemistry , Cell Differentiation/drug effects , Cell Line , Dendritic Cells/immunology , Dendritic Cells/metabolism , Gene Expression Regulation/drug effects , Humans , Interleukin-12/biosynthesis , Lymphocyte Activation/drug effects , MAP Kinase Signaling System/drug effects , Receptors, CCR7/metabolismABSTRACT
Ba(Ni_{1-x}Co_{x})_{2}As_{2} is a structural homologue of the pnictide high temperature superconductor, Ba(Fe_{1-x}Co_{x})_{2}As_{2}, in which the Fe atoms are replaced by Ni. Superconductivity is highly suppressed in this system, reaching a maximum T_{c}=2.3 K, compared to 24 K in its iron-based cousin, and the origin of this T_{c} suppression is not known. Using x-ray scattering, we show that Ba(Ni_{1-x}Co_{x})_{2}As_{2} exhibits a unidirectional charge density wave (CDW) at its triclinic phase transition. The CDW is incommensurate, exhibits a sizable lattice distortion, and is accompanied by the appearance of α Fermi surface pockets in photoemission [B. Zhou et al., Phys. Rev. B 83, 035110 (2011)PRBMDO1098-012110.1103/PhysRevB.83.035110], suggesting it forms by an unconventional mechanism. Co doping suppresses the CDW, paralleling the behavior of antiferromagnetism in iron-based superconductors. Our study demonstrates that pnictide superconductors can exhibit competing CDW order, which may be the origin of T_{c} suppression in this system.
ABSTRACT
A bone-remodeling imbalance induced by increased bone resorption and osteoclast formation causes skeletal diseases such as osteoporosis. Induction of osteogenic differentiation of bone marrow stromal cells (BMSCs) leads to bone regeneration. Many researchers have tried to develop new adjuvants as specific stimulators of bone regeneration for therapeutic use in patients with bone resorption. We tried to develop a new adjuvant that has stronger osteogenic differentiation-promoting activity than bone morphogenetic proteins (BMPs). In this study, we identified a new peptide, which we called bone-forming peptide (BFP)-3, derived from the immature precursor of BMP-7. Upon osteogenic differentiation, BMSCs treated with BFP-3 exhibited higher alkaline phosphatase (ALP) activity and mineralization ability and significantly up-regulated expression of osteogenic genes such as ALP, osteocalcin (OC), Osterix, and Runx2 compared with control BMSCs. Furthermore, fluorescence-activated cell sorting (FACS) and immunofluorescence analyses demonstrated that BFP-3 treatment up-regulated CD44 expression. Interestingly, extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad1/5/8 phosphorylation was increased by BFP-3 treatment during osteogenic differentiation. Furthermore, BFP-3-induced osteogenic differentiation was significantly decreased by treatment with ERK1/2- and Smad-specific inhibitors. These results suggest that BFP-3 plays an important role in regulating osteogenic differentiation of BMSCs through increasing levels of osteogenic-inducing factors and regulating the ERK1/2 and Smad1/5/8 signaling pathways. Our finding indicates that BFP-3 may be a potential new therapeutic target for promoting bone formation.
Subject(s)
Bone Marrow Cells/cytology , Bone Morphogenetic Protein 7/metabolism , Cell Differentiation/drug effects , Gene Expression Regulation/drug effects , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Peptide Fragments/pharmacology , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cells, Cultured , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Signal Transduction/drug effects , Smad1 Protein/genetics , Smad1 Protein/metabolism , Smad5 Protein/genetics , Smad5 Protein/metabolism , Smad8 Protein/genetics , Smad8 Protein/metabolismABSTRACT
Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP(+) treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders.
Subject(s)
Astrocytes/metabolism , Bee Venoms/therapeutic use , MPTP Poisoning/metabolism , MPTP Poisoning/prevention & control , Neuroprotective Agents/therapeutic use , Animals , Astrocytes/drug effects , Astrocytes/pathology , Bee Venoms/pharmacology , Cells, Cultured , Female , MPTP Poisoning/pathology , Male , Mice , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , Pregnancy , Random Allocation , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
Grateloupia lanceolata is a red alga native to coastal areas of East Asia. In this study, extract from G. lanceolata (EGL) was investigated for suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. EGL was found to have anti-inflammatory properties with the inhibition of nitric oxide (NO), pro-inflammatory cytokine production, and MAPK signaling in LPS-induced RAW 264.7 macrophages. Moreover, treatment of RAW 264.7 macrophage with EGL inhibited LPS-induced IL-1ß production in a dose-dependent manner. These inhibitory effects were found with the blockage of p38 mitogen-activated protein kinases (MAPK), extracellular signal regulated kinases 1 and 2 (ERK1/2), and also c-Jun N-terminal kinases 1 and 2 (JNK1/2). These results indicated that anti-inflammatory actions of EGL in RAW 264.7 macrophages involved in the inhibition of LPS-induced p38MAPK/ERK/JNK signaling pathways. In addition, our findings suggest that EGL holds great promise for use in the treatment of various inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Macrophages/drug effects , Nitric Oxide/antagonists & inhibitors , Plant Extracts/pharmacology , Rhodophyta/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Cell Line , Gene Expression Regulation , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/metabolism , Mice , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 8/antagonists & inhibitors , Mitogen-Activated Protein Kinase 8/genetics , Mitogen-Activated Protein Kinase 8/metabolism , Mitogen-Activated Protein Kinase 9/antagonists & inhibitors , Mitogen-Activated Protein Kinase 9/genetics , Mitogen-Activated Protein Kinase 9/metabolism , Nitric Oxide/biosynthesis , Plant Extracts/chemistry , Signal Transduction , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Inflammation is major symptom of the innate immune response by infection of microbes. Macrophages, one of immune response related cells, play a role in inflammatory response. Recent studies reported that various natural products can regulate the activation of immune cells such as macrophage. Sargassum horneri (Turner) C. Agardh is one of brown algae. Recently, various seaweeds including brown algae have antioxidant and anti-inflammatory effects. However, anti-inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown. In this study, we investigated anti-inflammatory effects of ethanolic extract of Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with 70% ethanol and then lyophilized at -40 °C. ESH was not cytotoxic to RAW 264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage activation was significantly decreased by the addition of 200 µg/mL of ESH. Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1ß, and pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory effects by inhibiting ERK, p-p38 and NF-κB phosphorylation. In addition, ESH inhibited the release of IL-1ß in LPS-stimulated macrophages. These results suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage activation via the inhibition of ERK, p-p38, NF-κB, and pro-inflammatory gene expression.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Macrophage Activation/drug effects , Macrophage Activation/immunology , Macrophages/immunology , Macrophages/metabolism , NF-kappa B , Plant Extracts/pharmacology , Sargassum/chemistry , Signal Transduction , Animals , Cell Line , Cell Survival , Cytokines/genetics , Cytokines/metabolism , Enzyme Activation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation/drug effects , Inflammation Mediators/metabolism , Lipopolysaccharides/immunology , Macrophages/drug effects , Mice , NF-kappa B/metabolism , Nitric Oxide/metabolismABSTRACT
Anaphylaxis is a rapidly occurring allergic reaction to any foreign substance, including venom from insects, foods and medications, which may cause fatalities. To prevent anaphylaxis, these triggers must be avoided. However, avoidance of numerous triggers is difficult. For this reason, the development of immunotherapeutic adjuvants that suppress the allergic response is important for anaphylaxis control. Mast cells are one of the major inflammatory cells involved in the inflammatory response, which secrete several inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and recruits other immune cells. Mast cells are also involved in a number of diseases, such as sinusitis, rheumatoid arthritis and asthma. Genistein, a phytoestrogen, has been reported to have anti-oxidative and anti-inflammatory activities. However, the effects of genistein on the anti-inflammatory response of mast cells remain unknown. In the present study, the anti-inflammatory effects of genistein on mast cells were investigated. Genistein significantly decreased IL-6 and IL-1ß mRNA levels, as well as IL-6 production in PMA/A23187-induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187-induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.
Subject(s)
Cytokines/metabolism , Genistein/pharmacology , Inflammation Mediators/metabolism , MAP Kinase Signaling System/drug effects , Mast Cells/drug effects , Blotting, Western , Calcimycin/pharmacology , Cell Line, Tumor , Cytokines/genetics , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Neoplastic/drug effects , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Mast Cells/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Phosphorylation/drug effects , Phytoestrogens/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Tetradecanoylphorbol Acetate/pharmacology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Oxidative stress has been proposed to be a major cause of aging and many age-related diseases. Peroxynitrite (ONOO(-)), formed from the reaction of superoxide ((â¢)O2 (-)) and nitric oxide (NO), is a cytotoxic species that can oxidize various cellular components, such as proteins, lipids, and DNA. The present study investigated whether dimethyl lithospermate (DML), isolated from Salvia miltiorrhiza, modulates age-related increases of ONOO(-), NO, and reactive species (RS) levels and expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). For this study, 20-month-old rats were intraperitoneally injected with 5 or 10 mg/kg/day of DML, and 6-month-old rats were used as young control animals. Our results indicated that DML reduces ONOO(-) levels in a dose-dependent manner. The data also revealed that DML has significant inhibitory effects on NO metabolites and RS generation in a dose-dependent manner during aging. Furthermore, the results of Western blot analysis revealed that DML treatment reduces age-associated increases in COX-2 and iNOS expressions. Thus, this study found that DML caused the decrease of renal oxidative stress and COX-2 and iNOS expressions in aged rats. The significance of the present study is the finding of DML in its potential application against the aging process.
Subject(s)
Aging/metabolism , Antioxidants/therapeutic use , Benzofurans/therapeutic use , Cyclooxygenase 2/biosynthesis , Nitric Oxide Synthase Type II/biosynthesis , Oxidative Stress/drug effects , Animals , Antioxidants/administration & dosage , Antioxidants/isolation & purification , Benzofurans/administration & dosage , Benzofurans/isolation & purification , Down-Regulation , Male , Nitric Oxide/metabolism , Peroxynitrous Acid/metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Salvia miltiorrhiza/chemistryABSTRACT
Ginsenoside Rc (Rc), a protopanaxadiol type ginsenoside, is the active component mainly responsible for the therapeutic and pharmacologic properties of ginseng, which are derived from its suppression of superoxide-induced free radicals. Forkhead box O (FoxO1) regulates various genes involved in cellular metabolism related to cell death and response to oxidative stress, and Rc is known to prevent FoxO1 phosphorylation by activation of PI3K/Akt and subsequent inhibition of AMP-activated protein kinase (AMPK) in cells exposed to tert-butylhydroperoxide (t-BHP). In the current study, we attempted the mechanism of increased catalase expression by Rc through inhibition of FoxO1 activation resulting from t-BHP-induced production of reactive species (RS). We found that overexpression of catalase induced by Rc resulted in suppression of RS production in kidney human embryo kidney 293T cells (HEK293T) cells, and that oxidative stress induced activation of PI3K/Akt and inhibition of the AMPK pathway and FoxO1 phosphorylation, leading to down-regulation of catalase, a FoxO1-targeting gene. In addition, treatment of HEK293T cells with Rc resulted in cAMP-response element-binding protein (CREB)-binding protein (CBP) regulated FoxO1 acetylation. Our results suggest that Rc modulates FoxO1 phosphorylation through activation of PI3K/Akt and inhibition of AMPK and FoxO1 acetylation through interaction with CBP and SIRT1, and that this leads to upregulation of catalase under conditions of oxidative stress.
Subject(s)
Forkhead Transcription Factors/physiology , Ginsenosides/pharmacology , Oxidative Stress/drug effects , Panax , Proto-Oncogene Proteins c-akt/physiology , Dose-Response Relationship, Drug , Forkhead Box Protein O1 , HEK293 Cells , Humans , Oxidative Stress/physiologyABSTRACT
Baicalin from Scutellaria baicalensis is a major flavonoid constituent found in the traditional Chinese medicinal herb Baikal skull cap. It has been widely used for the treatment of various diseases such as pneumonia, diarrhea, and hepatitis. Recent studies have demonstrated that baicalin possesses a wide range of pharmacological and biological activities, including anti-inflammatory, anti-microbial, anti-oxidant, and anti-tumor properties. Specifically, its anti-inflammatory activity has been estimated in various animal models of acute and chronic inflammation; however, its effects on dendritic cells (DCs) maturation and immuno-stimulatory activities are still unknown. In this study, we attempted to determine whether baicalin could influence DC surface molecule expression, antigen uptake capacity, cytokine production, and capacity to induce T-cell differentiation. Baicalin was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II as well as the levels of interleukin-12 production in lipopolysaccharide stimulated DCs. Moreover, baicalin-treated DCs showed an impaired induction of the T helper type 1 immune response and a normal cell-mediated immune response. These findings provide important understanding of the immunopharmacological functions of baicalin and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Differentiation/drug effects , Dendritic Cells/drug effects , Flavonoids/pharmacology , Scutellaria baicalensis , Th1 Cells/drug effects , Animals , B7-1 Antigen/biosynthesis , B7-2 Antigen/biosynthesis , Cells, Cultured , Dendritic Cells/cytology , Dendritic Cells/immunology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Flavonoids/biosynthesis , Interleukin-12/biosynthesis , Lipopolysaccharides/pharmacology , Major Histocompatibility Complex/genetics , Male , Mice , Th1 Cells/cytology , Th1 Cells/immunologyABSTRACT
Osteoporosis is a reduction in skeletal mass due to an imbalance between bone formation and bone resorption. Many researchers have tried to develop adjuvants as specific suppressors of bone resorption and stimulators of bone formation for therapeutic purposes in patients with osteoporosis. Therefore, specific stimulators on bone formation are one of therapeutic significance in the treatment of osteoporosis. Until now, the regulation of bone generation has been the focus of bone morphogenetic protein-7 (BMP-7) investigation from mature form. However, new peptides from immature form which has osteogenic activity has not been reported and developments of these proteins are still remained. In this study, we found a new peptide sequence, called bone forming peptide-1 (BFP-1) and have more high activities of osteogenic differentiation compared with BMP-7. BFP-1-treated multipotent bone marrow stromal stem cells (MBSCs) induced the expression levels and activity of alkaline phosphatase (ALP). Moreover, BFP-1 enhanced the levels of CD44, CD47 and CD51 expression as well as increased Ca(2+) content in MBSCs. In current study, radiography at 8 weeks revealed that BFP-1 pretreated-MBSC transplanted animals had strongly increased bone formation compared to that in the BMP-7 pretreated MBSC transplanted animals. Our finding indicates a new insight into peptides from the immature region of BMP-7 can also be useful in the development of adjuvant therapies for bone-related diseases.
Subject(s)
Bone Morphogenetic Protein 7/biosynthesis , Osteogenesis/physiology , Peptide Fragments/chemistry , Tissue Engineering/methods , Amino Acid Sequence , Biomarkers/metabolism , Bone Morphogenetic Protein 7/chemistry , Bone Regeneration , Bone and Bones/metabolism , CD47 Antigen/biosynthesis , Calcium/chemistry , Cell Survival , Dose-Response Relationship, Drug , Humans , Hyaluronan Receptors/biosynthesis , Integrin alphaV/biosynthesis , Molecular Sequence Data , Osteoporosis , Peptides/chemistry , Protein Structure, Tertiary , Regeneration , Stem Cells/cytology , Tetrazolium Salts/pharmacology , Thiazoles/pharmacologyABSTRACT
Osteoporosis is a reduction in skeletal mass due to an imbalance between bone formation and bone resorption. Therefore, the identification of specific stimulators of bone formation is of therapeutic significance in the treatment of osteoporosis. Salicylideneamino-2-thiophenol (Sal-2) consists of two benzene rings, has been reported to possess antioxidant activity, and is an effective remedy for fever and rheumatic diseases. However, until now the effects of osteoblastic bone formation by Sal-2 were unknown. In this study, we investigated the effects of Sal-2 on osteogenic differentiation of multipotent bone marrow stromal stem cells by alizarin red S staining for osteogenic differentiation, RT-PCR and western blot for alkaline phosphatase (ALP) activity and signaling pathways, FACS analysis and immunofluorescence staining for CD44 and CD51 expression, calcium assays, and immunofluorescence staining for signaling pathways. We found that Sal-2 enhanced the osteogenic differentiation of multipotent bone marrow stromal stem cells. Sal-2 treatment induced the expression and activity of ALP, and enhanced the levels of CD44 and CD51 expression as well as Ca2+ content, in multipotent bone marrow stromal stem cells. Moreover, we found that Sal-2-induced osteogenic differentiation and expression of osteogenesis-related molecules involve the activation of the MAPK and nuclear factor-κB pathways. Our findings provide insight into both the mechanism and effects of Sal-2 on osteogenic differentiation and demonstrate that Sal-2 may be a beneficial adjuvant in stimulating bone formation in osteoporotic diseases.
Subject(s)
Cell Differentiation/drug effects , Multipotent Stem Cells/drug effects , Osteogenesis/drug effects , Salicylates/pharmacology , Sulfhydryl Compounds/pharmacology , Alkaline Phosphatase/biosynthesis , Alkaline Phosphatase/metabolism , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Calcium/analysis , Cell Differentiation/physiology , Cell Line , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Hyaluronan Receptors/biosynthesis , Integrin alphaV/biosynthesis , MAP Kinase Signaling System/drug effects , Multipotent Stem Cells/metabolism , NF-kappa B/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Quercetin is found to be the most active of the flavonoids in studies and many medicinal plants owe much of their activity to their high Quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 were master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether Quercetin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in OVA-induced asthma model mice. Quercetin reduced the increased levels of IL-4, Th2 cytokine production in OVA-sensitized and -challenged mice. The other side, it increased IFN-gamma, Th1 cytokine production in Quercetin administrated mice. We also examined to ascertain whether Quercetin could influence Eosinophil peroxidase (EPO) activity. The administration of Quercetin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Quercetin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Quercetin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of Quercetin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Asthma/immunology , Quercetin/pharmacology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , Asthma/pathology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Eosinophil Peroxidase/metabolism , Eosinophils/drug effects , Eosinophils/immunology , Female , GATA3 Transcription Factor/antagonists & inhibitors , GATA3 Transcription Factor/immunology , GATA3 Transcription Factor/metabolism , Interferon-gamma/drug effects , Interferon-gamma/metabolism , Interleukin-4/antagonists & inhibitors , Interleukin-4/biosynthesis , Interleukin-4/immunology , Interleukin-5/antagonists & inhibitors , Interleukin-5/biosynthesis , Interleukin-5/immunology , Lung/immunology , Lung/pathology , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Ovalbumin/pharmacology , T-Box Domain Proteins/immunology , T-Box Domain Proteins/metabolism , Th1 Cells/drug effects , Th2 Cells/drug effectsABSTRACT
The primary objective of this study was to evaluate the ability and mechanism of action of kaempferol, which is contained in extracts from Nelumbo nucifera, a well-known Oriental herb used in traditional medicine, with regard to the inhibition of iNOS and TNF-alpha expression in aged rat gingival tissues. We conducted an investigation into the age-related effects of kaempferol on reactive oxygen species (ROS) and GSH oxidative status in samples of aged gingival tissues. Western blotting was conducted in order to determine the expression of iNOS, TNF-alpha, p38 MAPK, NIK/IKK, p65 and IkappaBalpha in the sample tissues. Electrophoretic mobility shift assays (EMSA) were conducted in an effort to characterize the binding activities of NF-kappaB transcription factors in the aged rat gingival nuclear extracts. Our results indicate that kaempferol reduced ROS levels and augmented GSH levels in a dose-dependent manner in the aged gingival tissues. Kaempferol was shown to effect a significant reduction in iNOS and TNF-alpha protein levels, as compared to control gingival tissue samples. The results of Western blot analysis revealed that kaempferol treatment effected the reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues, attenuated the NF-kappaB nuclear binding activity. Kaempferol may inhibit ROS generation via the inhibition of iNOS and TNF-alpha expression in aged gingival tissues, via the modulation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways.