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1.
Food Funct ; 10(11): 7091-7102, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31617532

RESUMO

Cranberry volatiles have received little attention for health-promoting properties. In this study, we compared the inhibitory effects of cranberry polyphenol and volatile extracts and volatile standards on nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophages. Polyphenols were analyzed by HPLC/HPLC-MS and volatiles were analyzed by GC/GC-MS. The inhibition of NO production of the fresh cranberry polyphenol and volatile extracts and α-terpineol, linalool, linalool oxide, and eucalyptol standards at 2, 4, and 8-fold dilutions of their original concentrations in fresh cranberries was evaluated by treating these extracts/standards for 1 h before or after LPS application for 24 h. After inducing inflammation with LPS, the polyphenol treatments (317.8 and 635.7 µg g-1) and 1.8 µg g-1 volatile treatment lowered NO levels 46-62% compared to the positive control (P < 0.05). When the cells were treated with polyphenol and volatile extracts before inducing inflammation, the 635.7 µg g-1 and 317.8 µg g-1 polyphenol treatments and 1.8 µg g-1 and 0.9 µg g-1 volatile treatments lowered NO levels (13-52%) compared to the positive control (P < 0.05). Polyphenol and volatile extracts from cranberry were effective in reducing NO production whether applied before or after the application of LPS. α-Terpineol at a concentration found in fresh cranberries (1.16 µg mL-1) was also found to be effective in reducing NO production whether cells were treated before or after application of LPS. Future studies are needed to reveal the mechanisms by which volatile compounds, especially α-terpineol act to mitigate inflammation and to determine the bioavailability of terpenes.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/imunologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vaccinium macrocarpon/química , Animais , Frutas/química , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Células RAW 264.7
2.
BMC Complement Altern Med ; 19(1): 252, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506082

RESUMO

BACKGROUND: Turmeric is commonly used as a dietary treatment for inflammation, but few studies have evaluated the direct effect of turmeric on cartilage. The purpose of this study was to characterize cartilage explants' inflammatory responses to lipopolysaccharide in the presence of a simulated biological extract of turmeric. METHODS: Turmeric was incubated in simulated gastric and intestinal fluid, followed by inclusion of liver microsomes and NADPH. The resulting extract (TURsim) was used to condition cartilage explants in the presence or absence of lipopolysaccharide. Explants were cultured for 96 h (h); the first 24 h in basal tissue culture media and the remaining 72 h in basal tissue culture media containing TURsim (0, 3, 9 or 15 µg/mL). Lipopolysaccharide (0 or 5 µg/mL) was added for the final 48 H. media samples were collected immediately prior to lipopolysaccharide exposure (0 h) and then at 24 and 48 h after, and analyzed for prostaglandin E2 (PGE2), glycosaminoglycan (GAG), and nitric oxide (NO). Explants were stained with calcein-AM for an estimate of live cells. Data were analyzed using a 2-way repeated measures (GAG, PGE2, NO) or 1-way ANOVA without repeated measures (viability). Significance accepted at p < 0.05. RESULTS: TURsim significantly reduced PGE2, NO and GAG, and calcein fluorescence was reduced. CONCLUSIONS: These data contribute to the growing body of evidence for the utility of turmeric as an intervention for cartilage inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Cartilagem/efeitos dos fármacos , Curcuma/química , Extratos Vegetais/farmacologia , Animais , Cartilagem/imunologia , Dinoprostona/imunologia , Glicosaminoglicanos/imunologia , Técnicas In Vitro , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/imunologia , Masculino , Óxido Nítrico/imunologia , Ratos , Suínos
3.
J Med Microbiol ; 68(11): 1629-1640, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553301

RESUMO

Introduction. ML1899 is conserved in all mycobacterium sp. and is a middle member of mle-ML1898 operon involved in mycolic acid modification.Aim. In the present study attempts were made to characterize ML1899 in detail.Methodology. Bioinformatics tools were used for prediction of active-site residues, antigenic epitopes and a three-dimensional model of protein. The gene was cloned, expressed and purified as His-tagged protein in Escherichia coli for biophysical/biochemical characterization. Recombinant protein was used to treat THP-1 cells to study change in production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and chemokines using flowcytometry/ELISA.Results. In silico analysis predicted ML1899 as a member of α/ß hydrolase family with GXSXG-motif and Ser126, His282, Asp254 as active-site residues that were confirmed by site-directed mutagensis. ML1899 exhibited esterase activity. It hydrolysed pNP-butyrate as optimum substrate at pH 8.0 and 50 °C with 5.56 µM-1 min-1 catalytic efficiency. The enzyme exhibited stability up to 60 °C temperature and between pH 6.0 to 9.0. K m, V max and specific activity of ML1899 were calculated to be 400 µM, 40 µmoles min-1 ml-1 and 27 U mg- 1, respectively. ML1899 also exhibited phospholipase activity. The protein affected the survival of macrophages when treated at higher concentration. ML1899 enhanced ROS/NO production and up-regulated pro-inflammatory cytokines and chemokine including TNF-α, IFN-γ, IL-6 and IL-8 in macrophages. ML1899 was also observed to elicit humoral response in 69 % of leprosy patients.Conclusion. These results suggested that ML1899, an esterase could up-regulate the immune responses in favour of macrophages at a low concentration but kills the THP-1 macrophages cells at a higher concentration.


Assuntos
Proteínas de Bactérias/imunologia , Esterases/imunologia , Hanseníase/microbiologia , Mycobacterium leprae/enzimologia , Sequência de Aminoácidos , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Citocinas/genética , Citocinas/imunologia , Estabilidade Enzimática , Esterases/química , Esterases/genética , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cinética , Hanseníase/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Mycobacterium leprae/química , Mycobacterium leprae/genética , Mycobacterium leprae/imunologia , Óxido Nítrico/imunologia , Espécies Reativas de Oxigênio/imunologia , Alinhamento de Sequência
4.
Food Funct ; 10(9): 6135-6146, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31497826

RESUMO

Osteoarthritis (OA) is a degenerative joint disease, whose progression is closely related to the inflammatory environment. Urolithin A (UA), a natural metabolite of a class of compounds (ellagitannins and ellagic acid) found in pomegranates and other fruits and nuts, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of UA in OA development is still unclear. In the present study, we examined the latent mechanism of UA and its protective role in the progression of OA by both in vitro and in vivo experiments. In vitro, UA inhibited the interleukin-1 beta (IL-1ß) induced over-production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in a concentration-dependent manner in human OA chondrocytes. Furthermore, by downregulating the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), UA attenuated the degradation of the extracellular matrix (ECM) induced by IL-1ß. Mechanistically, UA was found to suppress the activation of PI3K/Akt/NF-κB pathways. In vivo, in a surgically induced mouse OA model, UA-induced protective effects in OA development could be detected. In summary, this research suggested that UA may be adopted as a new therapeutic agent for the treatment of OA.


Assuntos
Cumarínicos/administração & dosagem , Interleucina-1beta/imunologia , NF-kappa B/imunologia , Osteoartrite/tratamento farmacológico , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Óxido Nítrico/imunologia , Osteoartrite/genética , Osteoartrite/imunologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
5.
Food Funct ; 10(10): 6589-6603, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31552984

RESUMO

In the current study, we identified and characterized a novel water-soluble polysaccharide (JNY2PW) with significant immunoregulatory effects and no apparent overall toxicity. JNY2PW, which was isolated from Arca inflata, belongs to a novel class of α-glucans with a molecular weight of 5.25 × 107 Da. Its backbone is composed of (1 → 4)-linked α-d-glucopyranosyl residues and a single (1 → 6)-α-d-glucopyranosyl branched unit for every five α-d-glucopyranosyl residues, showing a comb-like α-d-glucan with intensive short branches. Using in vitro models, we demonstrated that JNY2PW exerts significant immunoregulatory effects by promoting the production of nitric oxide, interleukin-6, and tumor necrosis factor α. The pathway involves the activation of the TLR4-MAPK/NF-κB signaling cassette in murine RAW264.7 macrophages. In an in vivo immunosuppressive mice model induced by cyclophosphamide treatment, we found that the JNY2PW treatment produced good antitumor activity, comparable to that of chemotherapy by doxycycline in murine breast carcinoma 4T1-bearing mice, but devoid of any observable side effects (e.g. weight loss) related with doxycycline treatment. The anti-tumor mechanism of JNY2PW may involve an overall enhancement in the immune responses of the mice to tumors. These results indicate that JNY2PW possesses potential as an adjuvant to existing chemotherapy and current immune-oncology treatment.


Assuntos
Arcidae/química , Glucanos/administração & dosagem , Glucanos/química , Fatores Imunológicos/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Feminino , Glucanos/isolamento & purificação , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/imunologia , Neoplasias/genética , Neoplasias/imunologia , Óxido Nítrico/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
BMC Complement Altern Med ; 19(1): 262, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547810

RESUMO

BACKGROUND: Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. One of the plants with great medicinal potentials is Diospyros kaki which is mainly cultivated in Asian countries including Korea, Japan, and China. Astringent D. kaki is a wild species with an astringent taste until they are Ripened. kaki calyx is a traditional Korean medicine (TKM) made from the stalks of astringent D. kaki and is used in treating bed-wetting, vomiting, and hiccupping. The present study was designed to investigate the potential anti-inflammatory activities of astringent D. kaki stalks based on cultivar types and stages of maturity. METHODS: The anti-inflammatory effects of the stalk extracts of local astringent D. kaki cultivar species were evaluated on RAW 264.7 cells. Cell viability was measured using a Cell Counting Kit-8 (CCK8) method. The anti-inflammatory effects were determined by measuring the nitric oxide (NO) concentration of the supernatant. Cellular signaling pathways were determined by quantitative polymerase chain reactions of inducible nitric oxide synthase (iNOS). Protein expression of iNOS and phospho-p65 was determined using western blot, and the nuclear localization of p65 was determined using confocal imaging in RAW 264.7 cells. RESULTS: We found that the stage 1 (8-9 month) samples all showed a high percentage of tannic acid content and Gojongsi (Hamyang) stalks had the highest content. The stage 1 samples also showed the highest inhibition of NO production. Decreases in the expression of iNOS and phosphorylated p65, and in the nuclear localization of p65, were dose-dependent. All the extracts were nontoxic under 100 µg/ml concentration. CONCLUSION: This study provides insight into the changes in tannic acid content in astringent D. kaki and their anti-inflammatory effects, in relation to their stage of maturity. These results are expected to be useful in the verification of the efficacy of oriental medicine and the timing of proper harvest for medical use.


Assuntos
Anti-Inflamatórios/farmacologia , Diospyros/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Diospyros/classificação , Diospyros/crescimento & desenvolvimento , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Extratos Vegetais/química , Caules de Planta/química , Caules de Planta/classificação , Caules de Planta/crescimento & desenvolvimento , Células RAW 264.7 , República da Coreia
7.
Food Funct ; 10(9): 5827-5842, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31463498

RESUMO

In this study, we aim to assess possible impacts of essential oil (SEO) from Schisandra chinensis (Turcz.) Baill. (S. chinensis) on mice with cognition impairment. Our data showed that SEO improved the cognitive ability of mice with Aß1-42 or lipopolysaccharides (LPS)-induced Alzheimer's disease (AD) and suppressed the production of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in the hippocampus. Furthermore, SEO inhibited p38 activation, but had little effect on other signaling proteins in the MAPK family, such as extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK). The SEO and BV-2 microglia co-culture was performed to further confirm the anti-inflammatory activity of SEO. The data showed that SEO decreased nitric oxide (NO) levels in LPS-stimulated BV-2 microglia and significantly blocked LPS-induced MAPKs activation. Taken together, these findings suggested that SEO produces anti-AD effects on AD mice partly by modulating neuroinflammation through the NF-κB/MAPK signaling pathway.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Óleos Voláteis/administração & dosagem , Óleos Vegetais/administração & dosagem , Schisandra/química , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Cognição/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Microglia/química , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
8.
Food Funct ; 10(9): 5779-5788, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31454011

RESUMO

Chronic inflammation depends on inflammatory mediators produced by activated macrophages and is the common pathological basis for various diseases. Turmeronol is a sesquiterpenoid found in the spice turmeric (Curcuma longa), which is known to have anti-inflammatory activity. To elucidate the anti-inflammatory mechanism of turmeronol, we investigated the influence of turmeronol A and turmeronol B in mouse macrophages (RAW264.7 cells) stimulated with lipopolysaccharide (LPS). Pretreatment of RAW264.7 cells with either turmeronol A or B significantly inhibited LPS-induced production of prostaglandin E2 and nitric oxide, as well as expression of mRNAs for the corresponding synthetic enzymes. In addition, the turmeronols significantly inhibited LPS-induced upregulation of interleukin-1ß, interleukin-6, and tumor necrosis factor-α at the mRNA and protein levels. Both turmeronols also inhibited nuclear translocation of nuclear factor κB (NF-κB), with a similar time course to the NF-κB inhibitor pyrrolidine dithiocarbamate, but not curcumin (another NF-κB inhibitor). Thus, both turmeronols prevented activation of macrophages and inflammatory mediator production, possibly by suppressing activation of NF-κB, and therefore have potential for use in preventing chronic inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Curcuma/química , Inflamação/imunologia , Macrófagos/efeitos dos fármacos , NF-kappa B/imunologia , Extratos Vegetais/farmacologia , Animais , Dinoprostona/imunologia , Inflamação/tratamento farmacológico , Inflamação/genética , Mediadores da Inflamação/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/efeitos adversos , Macrófagos/imunologia , Camundongos , NF-kappa B/genética , Óxido Nítrico/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
9.
J Med Food ; 22(9): 885-895, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274380

RESUMO

We have previously demonstrated the hepatoprotective effect of Schisandra chinensis polysaccharides (SCP) against the liver injury induced by alcohol, high-fat diet, and carbon tetrachloride in mice. In this study, we investigated the effect of SCP against the immunological liver injury induced by concanavalin A (Con A) in mice. The results showed that SCP could significantly reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of mice with immunological liver injury. SCP could significantly decrease the content of malondialdehyde (MDA) and nitric oxide (NO) and increase the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver tissue. SCP could significantly increase the number of CD4+ and decrease the number of CD8+ in the peripheral blood, and elevate the ratio of CD4+/CD8+. SCP could significantly downregulate the expression of Kelch-like ECH-associated protein 1 (Keap1) and upregulate the expression of nuclear factor-erythroid 2-related factor2 (Nrf2) and downstream gene heme oxygenase-1 (HO-1), and downregulate the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) proteins. This study indicates that SCP can reduce the release of a large number of inflammatory factors to inhibit the oxidative stress in mice with the immunological liver injury induced by Con A, and its mechanism is closely related to the regulation of Nrf2/antioxidant response element and TLR4/NF-κB signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Polissacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Schisandra/química , Receptor 4 Toll-Like/imunologia , Animais , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Óxido Nítrico/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
10.
Int Immunopharmacol ; 75: 105750, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330445

RESUMO

Telmisartan, widely prescribed for the treatment of hypertension, has an anti-inflammatory property in addition to being an angiotensin II type 1 receptor antagonist. This study was carried out to explore the influence of telmisartan upon the elaboration of inflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) prepared from Prevotella intermedia, a periodontal pathogen, as well as its molecular mechanisms. Telmisartan significantly inhibited LPS-induced generation of inducible nitric oxide (NO) synthase-derived NO and interleukin-1ß (IL-1ß) as well as their gene expressions in RAW264.7 cells. Telmisartan treatment of LPS-activated cells significantly up-regulated arginase 1 (Arg-1) and chitinase-like 3 (Ym-1), which are specific markers of M2 macrophages. Telmisartan caused a significant increase in heme oxygenase-1 (HO-1) expression in cells stimulated with LPS, and its inhibitory action against NO production was reversed by treatment with SnPP, an HO-1 inhibitor. Phosphorylation of STAT1 and STAT3 induced by LPS was attenuated by telmisartan. Telmisartan inhibited LPS-induced generation of NO and IL-1ß independently of PPAR-γ activation. In addition, activation of NF-κB as well as JNK and p38 signaling induced by LPS was not modulated by telmisartan. In summary, telmisartan is a potent inhibitor of P. intermedia LPS-induced generation of NO and IL-1ß in RAW264.7 cells and promotes macrophage phenotype switching toward the M2 phenotype. Telmisartan may have potential to be developed into host modulatory agent for inflammatory periodontal disease, although additional studies are needed to confirm the therapeutic effect.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Inflamatórios/farmacologia , Interleucina-1beta/imunologia , Óxido Nítrico/imunologia , Prevotella intermedia , Telmisartan/farmacologia , Animais , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Interleucina-1beta/genética , Lipopolissacarídeos , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Células RAW 264.7
11.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340484

RESUMO

In order to enrich and separate three coumarins (columbianetin acetate, osthole and columbianadin) from Angelicae Pubescentis Radix (APR), an efficient method was established by combining macroporous resins (MARs) with preparative high-performance liquid chromatography (PHPLC). Five different macroporous resins (D101, AB-8, DA-201, HP-20 and GDX-201) were used to assess the adsorption and desorption characteristics of three coumarins. The result demonstrated that HP-20 resin possessed the best adsorption and desorption capacities for these three coumarins. Moreover, the adsorption dynamics profiles of three coumarins were well fitted to the pseudo second order equation (R2 > 0.99) for the HP-20 resin. The adsorption process was described by the three isotherms models including Langmuir (R2 > 0.98, 0.046 ≤ RL ≤ 0.103), Freundlich (R2 > 0.99, 0.2748 ≤ 1/n ≤ 0.3103) and Dubinin Radushkevich (R2 > 0.97). The contents of columbianetin acetate, osthole and columbianadin in the product were increased 10.69-fold, 19.98-fold and 19.68-fold after enrichment, respectively. Three coumarins were further purified by PHPLC and the purities of them reached above 98%. Additionally, the anti-inflammatory effects of these three coumarins were assessed by Lipopolysaccharide (LPS)-induced RAW 264.7 cells. It was found that the production of NO and MCP-1 was obviously inhibited by three coumarins. Columbianetin acetate, osthole and columbianadin could be used as potentially natural anti-inflammatory ingredients in pharmaceutical products. It was concluded that the new method combining MARs with PHPLC was efficient and economical for enlarging scale separation and enrichment of columbianetin acetate, osthole and columbianadin with anti-inflammatory effect from the APR extract.


Assuntos
Angelica/química , Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Medicamentos de Ervas Chinesas/química , Furocumarinas/farmacologia , Adsorção , Animais , Anti-Inflamatórios/isolamento & purificação , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/isolamento & purificação , Furocumarinas/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/imunologia , Porosidade , Células RAW 264.7 , Resinas Sintéticas/química
12.
J Surg Res ; 244: 241-250, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31301480

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) can provide a defense against ischemia-reperfusion (IR)-induced acute inflammation and barrier dysfunction in many organs. Because nitric oxide (NO) has been implicated as a trigger or mediator in the IPC mechanism and because neuronal NO synthase (nNOS) is a dominant isoform of NOS in the gastrointestinal tract, our aim was to investigate the role of nNOS in IPC-induced protection after mesenteric IR. MATERIALS AND METHODS: Intestinal IR was induced in sodium pentobarbital-anesthetized dogs by clamping the superior mesenteric artery for 60 min followed by 2 h of reperfusion (IR group; n = 7). In further groups, IPC was used (three cycles of 5-min ischemia/5-min reperfusion periods) before IR in the presence or absence of selective inhibition of nNOS with 7-nitroindazole (5 mg/kg, intravenously, in a bolus 15 min before IPC, n = 6 each). Changes in mesenteric vascular resistance, intramucosal pH (pHi), and small bowel motility were monitored. Plasma nitrite/nitrate levels, intestinal NO synthase activity, leukocyte accumulation, mast cell degranulation, and histologic injury were also determined. RESULTS: Ischemia significantly decreased mesenteric vascular resistance and pHi, whereas IR induced a temporary bowel hypermotility and acute inflammatory reaction. IPC facilitated pHi recovery, attenuated motility dysfunction, elevated NOS-dependent NO production, and reduced leukocyte accumulation, mast cell degranulation, and mucosal injury. Pretreatment with 7-nitroindazole halted the IPC-induced increase in NO availability, pHi recovery, and the anti-inflammatory and morphologic effects. CONCLUSIONS: Our data demonstrate that NO generated by intestinal nNOS plays a pivotal role in IPC-linked tissue protection by inhibiting an IR-related acute inflammatory response.


Assuntos
Mucosa Intestinal/imunologia , Precondicionamento Isquêmico/métodos , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/imunologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Degranulação Celular/imunologia , Modelos Animais de Doenças , Cães , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Masculino , Mastócitos/imunologia , Artéria Mesentérica Superior/cirurgia , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/etiologia
13.
Food Funct ; 10(8): 5059-5069, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31359010

RESUMO

As a chronic degenerative joint disease, osteoarthritis (OA) is clinically characterized by a high incidence, long-term pain, and limited joint activity but without effective preventative therapy. Troxerutin (Tx) is a natural flavonoid, also called vitamin P4, which is widely present in plants consumed as part of our daily diet, such as cereals, various fruits and vegetables, tea, and coffee, and possesses various biological activities, especially an anti-inflammatory effect. Here, we aimed to investigate the potential chondroprotection of Tx in experimental OA development. In in vitro studies, human chondrocytes were isolated and exposed in advanced glycation end-products (AGEs) to simulate OA development. It was found that Tx pretreatment inhibited the AGE-induced production of pro-inflammatory factors in chondrocytes, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Meanwhile, AGE-medicated extracellular matrix (ECM) degradation was decreased in Tx-pretreated chondrocytes. Furthermore, we found that Tx pretreatment suppressed the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in AGE-exposed chondrocytes. In vivo, Tx treatment prevented the narrowing of the joint space, the calcification of cartilage, and the loss of proteoglycans in the mouse OA model. In brief, Tx is considered as a potential therapeutic agent for OA.


Assuntos
Anti-Inflamatórios/administração & dosagem , Condrócitos/efeitos dos fármacos , Produtos Finais de Glicação Avançada/efeitos adversos , Hidroxietilrutosídeo/análogos & derivados , Osteoartrite/tratamento farmacológico , Animais , Condrócitos/imunologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Modelos Animais de Doenças , Humanos , Hidroxietilrutosídeo/administração & dosagem , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Osteoartrite/etiologia , Osteoartrite/genética , Osteoartrite/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
14.
J Agric Food Chem ; 67(32): 9070-9078, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31343168

RESUMO

In this study, an immunologically active novel microparticulate mushroom ß-glucan (PRA-1p) was prepared using an alkali-soluble glucan PRA-1 by an emulsification and cross-linking method. PRA-1 was a hyperbranched (1→3),(1→6)-ß-d-glucan with a degree of branching of 0.89, isolated from the sclerotia of Polyporus rhinocerus. PRA-1 had a rod-like conformation, while PRA-1p exhibited a monodisperse and homogeneous spherical conformation with a diameter ranging from 0.3 to 2.0 µm in water. PRA-1p significantly induced nitric oxide and reactive oxygen species production as well as morphological changes of murine macrophages (RAW 264.7 cells) and upregulated their phagocytic activity. Furthermore, PRA-1p treatment markedly enhanced the secretion of cytokines, including cutaneous T cell-attracting chemokine 27, granulocyte-colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, macrophage inflammatory protein 2, regulated on activation, normal T cell expressed and secreted, soluble tumor necrosis factor receptor 1, and tissue inhibitors of metalloproteinases. Activation of RAW 264.7 cells triggered by PRA-1p was associated with activation of inducible nitric oxide synthase, nuclear factor κB, extracellular signal-regulated kinase, and protein kinase B. This work suggests that novel PRA-1p derived from the mushroom sclerotia of P. rhinocerus has potential application as an immunostimulatory agent.


Assuntos
Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polyporus/química , beta-Glucanas/química , beta-Glucanas/farmacologia , Animais , Quimiocina CCL27/genética , Quimiocina CCL27/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fatores Imunológicos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Fagocitose/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Polyporus/imunologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , beta-Glucanas/isolamento & purificação
15.
BMC Complement Altern Med ; 19(1): 149, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238921

RESUMO

BACKGROUND: The kidney is an essential organ required by the body to perform several important functions. Nephrotoxicity is one of the most prevailing kidney complications that result from exposure to an extrinsic or intrinsic toxicant, which increase the need for the acquisition of proper remedies. Recently, natural remedies are gaining great attention owed to the fact that they have fewer side effects than most conventional drugs. METHODS: The current study recorded a new therapeutic role of the well-known medicinal plants for kidney stones [Ammi visnaga (AVE), Petroselinum crispum (PCE), Hordeum vulgare (HVE), and Cymbopogon schoenanthus (CSE)]. Hence, the aqueous extracts of these plants examined against CCl4-induced toxicity in mammalian kidney (Vero) cells. RESULTS: These extracts showed the presence of varying amounts of phenolic and triterpenoid compounds, as well as vitamin C. Owing to the antioxidant potential of these constituents, the extracts suppressed the CCl4-induced oxidative stress significantly (p < 0.05) by scavenging the reactive oxygen species and enhancing the cellular antioxidant indices. In addition, these extracts significantly (p < 0.05) reduced the CCl4-induced inflammation by inhibiting the gene expression of NF-кB, iNOS, and in turn the level of nitric oxide. Consequently, the morphological appearance of Vero cells, cellular necrosis, and the gene expression of kidney injury molecule-1 (a marker of renal injury) after these treatments were improved. The AVE improved CCl4-induced oxidative and inflammatory stress in Vero cells and showed a more potent effect than the commonly used alpha-Ketoanalogue drug (ketosteril) in most of the studied assays. CONCLUSION: Thus, the studied plant extracts, especially AVE can be considered as promising extracts in the management of nephrotoxicity and other chronic diseases associated with oxidative stress and inflammation.


Assuntos
Ammi/química , Cymbopogon/química , Hordeum/química , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Petroselinum/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Rim/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Sementes/química , Células Vero
16.
Mol Med Rep ; 20(1): 802-812, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180517

RESUMO

Microglia are the major immune cells in the central nervous system. Microglial activation can be beneficial or detrimental depending on the stimuli and the physiopathological environment. Microglial activation is involved in a variety of neurodegenerative disorders. Different anesthetic agents have exhibited diverse effects on microglial activation and the engulfment process. The anthocyanin callistephin has been demonstrated to have antioxidant and anti­inflammatory properties, and these were assessed in the present study, with a focus on its effect on microglial activation. Mouse microglial cells C8­4B were treated with 100 ng/µl lipopolysaccharide (LPS) and 1 ng/µl interferon­Î³. Cells were subsequently treated with 2% isoflurane, 100 µM callistephin or both. LPS promoted apoptosis in C8­B4 cells, and this was reduced following treatment with isoflurane and callistephin. LPS­treated C8­B4 cells also exhibited enhanced production of reactive oxygen species and nitric oxide, excessive engulfment and increased caspase 3/7 activity. These detrimental alterations were suppressed following co­treatment with isoflurane and callistephin. LPS­induced apoptosis was facilitated via the expression of B­cell lymphoma­2 like 1 and poly (ADP­ribose) polymerase, which were subsequently restored following treatment with isoflurane and callistephin. Callistephin was demonstrated to be involved in the modulation of inducible nitric oxide synthase, cytochrome c oxidase subunit 2, tumor necrosis factor­α and nuclear factor­κ B. Callistephin enhanced the protective effects of isoflurane by modulating engulfment and apoptosis in C8­B4 cells. The potential underlying mechanism was identified to be the suppression of p38 phosphorylation. The present study thus suggested that the negative effects on microglial activity induced by LPS were ameliorated following treatment with callistephin, which also enhanced the effects of isoflurane. Callistephin may therefore constitute a candidate drug agent that may target inflammatory and growth regulatory signaling pathways, thus ameliorating certain aspects of neurodegenerative diseases.


Assuntos
Antocianinas/farmacologia , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Inflamação/tratamento farmacológico , Isoflurano/farmacologia , Microglia/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Linhagem Celular , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Microglia/imunologia , Óxido Nítrico/imunologia , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio/imunologia
17.
Immun Inflamm Dis ; 7(3): 170-182, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207167

RESUMO

BACKGROUND: Heredity and environmental parameters jointly affect allergy development. Here, we used a Swedish prospective cohort to study the influence of heredity and factors usually associated with allergic disease and the development of allergic manifestations in combination with immunoglobulin E (IgE) sensitization at four different time points until 10 years of age. METHODS: Parents-to-be were characterized concerning allergy and their children (n = 281) were divided based on allergic heredity and followed from birth and clinically examined for IgE-associated allergic symptoms until 10 years of age. The relation between allergy and early-life parameters was analyzed by logistic regression. Group-wise comparisons were made by nonparametrical tests. RESULTS: Early life eczema and/or asthma in combination with IgE sensitization, was a strong indicator of allergy at a later time point. Further, the early occurrence of multiple allergic symptoms among IgE-sensitized children predisposed for a more complex allergic phenotype at later ages, independently of allergic heredity. At 10 years of age, allergic children had higher fractional exhaled nitrogen oxide (FeNO) levels, regardless of asthma, and FeNO levels were also influenced by heredity. Birth season was strongly associated with allergy development, but only in children with two allergic parents. CONCLUSION: Allergic eczema/asthma in early life, being born during the autumn/winter, having multiple allergic symptoms and two allergic parents were all strong predictors for having allergic diseases at 5 and 10 years of age. However, the allergic march seems to be independent of heredity, as IgE-mediated allergies follow the same trajectories in children with and without allergic heredity.


Assuntos
Asma/imunologia , Eczema/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Fatores Etários , Asma/diagnóstico , Criança , Pré-Escolar , Eczema/diagnóstico , Expiração , Feminino , Humanos , Hipersensibilidade/diagnóstico , Lactente , Recém-Nascido , Masculino , Óxido Nítrico/imunologia , Óxido Nítrico/metabolismo , Pais , Fenótipo , Estudos Prospectivos
18.
Int J Med Microbiol ; 309(5): 307-318, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178418

RESUMO

Mycobacterium abscessus (MAB) is an emerging, rapidly growing non-tuberculous Mycobacterium causing therapy-resistant pulmonary disease especially in patients with cystic fibrosis (CF). Smooth and rough colony type MAB can be isolated from infected patients whereby rough colony type MAB are more often associated with severe disease. Disease severity is also associated with an alternated type I interferon (IFN-I) response of the MAB-infected patients. However the relevance of this response for the outcome of MAB infection is still unknown. In this study, we analyzed the IFNß expression of murine macrophages infected with a MAB rough colony strain (MAB-R) isolated from a patient with progressive CF and compared it to macrophages infected with the MAB smooth colony type reference strain (MAB-S). We found that MAB-R infected macrophages expressed significantly more IFNß mRNA and protein than MAB-S infected macrophages. Higher IFNß induction by MAB-R was associated with higher TNF expression and intracellular killing while low IFNß induction was associated with lower TNF expression and persistence of MAB-S. IFNß induction was independent of the intracellular cGAS-STING recognition pathway. MAB appeared to be recognized extracellularly and induced IFNß expression via TLR2-TLR4-MyD88-TRIF-IRF3 dependent pathways. By using macrophages lacking the IFN-I receptor we demonstrate that MAB induced IFN-I response essentially contributed to restricting MAB-R and MAB-S infections by activating macrophage Nos2 expression and nitric oxide production. Thus IFN-I seem to influence the intrinsic ability of macrophages to control MAB infections. As MAB persists over long time periods in susceptible patients, our findings suggest that virulence of MAB strains is promoted by an insufficient IFN-I response of the host.


Assuntos
Interferon beta/imunologia , Macrófagos/microbiologia , Mycobacterium abscessus/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Óxido Nítrico/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Interações Hospedeiro-Patógeno/imunologia , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Micobactéria não Tuberculosa/imunologia , Infecções por Micobactéria não Tuberculosa/microbiologia , Óxido Nítrico Sintase Tipo II/genética , Escarro/microbiologia
19.
J Pharm Pharmacol ; 71(8): 1311-1323, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134626

RESUMO

OBJECTIVE: Mushroom crude polysaccharides offer a complete package of various medicinal activities. In this context, the present study aimed to unveil structural and biomedical properties of crude polysaccharide (MLHWP) obtained from an edible wild mushroom Macrocybe lobayensis (R. Heim) Pegler & Lodge. METHOD: Chemical characterization was accomplished with the help of spectrophotometry, Fourier-transform infrared spectroscopy, HPTLC and GC-MS. Immunomodulatory activity of the crude polysaccharide and its signalling mechanism was assessed using RAW 264.7 cells. Furthermore, antioxidant activity was analysed based on radical scavenging, metal ion chelating and reducing effect. KEY FINDINGS: Compositional study revealed that MLHWP possessed triple helical structure and its backbone consisted of ß-linked glucan along with xylose, rhamnose, mannose and galactose. Investigation on bioactive potency revealed that MLHWP augmented macrophage activity in terms of viability, phagocytosis, NO and ROS generation. Gene expression studies indicated that MLHWP signalled through TLR and modulated expression of immunomodulation-related genes including NF-κB, COX-2, IFN-γ, TNF-α, iNOS and Iκ-ßα. Besides, MLHWP displayed noticeable antioxidant potential as reflected in all investigating assays. CONCLUSIONS: Overall, the results portrayed possibility of MLHWP as pharmaceutical agent with multidimensional application.


Assuntos
Agaricales/imunologia , Macrófagos/imunologia , NF-kappa B/imunologia , Polissacarídeos/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/imunologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Polissacarídeos/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/imunologia , Transdução de Sinais/efeitos dos fármacos
20.
Immunopharmacol Immunotoxicol ; 41(2): 337-348, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31056974

RESUMO

Objective: The isochroman-type fungal metabolite 3,7-dimethyl-1,8-hydroxy-6-methoxyisochroman (DMHM) was isolated from the extracts of a marine-derived fungal strain of Penicillium sp. SF-6013. In this study, we investigated the effect of DMHM on inflammatory response. Materials and methods: Anti-inflammatory effects of DMHM were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, qRT-PCR, and western blot analysis. Results: DMHM revealed that it suppressed the production of prostaglandin E2 (PGE2), nitric oxide (NO), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) in LPS-stimulated RAW264.7 and BV2 cells. Furthermore, DMHM decreased the mRNA expression of pro-inflammatory cytokines including interleukin (IL)-1ß and IL-6. Therefore, DMHM was further investigated to elucidate the mechanisms of its anti-inflammatory properties; the results indicated that its effect was mediated by the suppression of the nuclear factor (NF)-κB and c-Jun N-terminal kinase (JNK) MAPK pathways. Furthermore, the anti-inflammatory activity of DMHM correlated with its induction of heme oxygenase-1 (HO)-1 expression via activation of the nuclear factor erythroid 2-like 2 (Nrf2) pathway. Discussion and conclusions: Collectively, the results of this study suggest that DMHM inhibited several inflammatory pathways including the NF-κB and MAPK pathways, and induced Nrf2-mediated HO-1 expression, demonstrating its potential usefulness for treating inflammatory and neuroinflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Cromanos/farmacologia , Heme Oxigenase-1/imunologia , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Membrana/imunologia , Fator 2 Relacionado a NF-E2/imunologia , Animais , Anti-Inflamatórios/química , Cromanos/química , Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Óxido Nítrico/imunologia , Penicillium/química , Células RAW 264.7
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