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1.
Gen Physiol Biophys ; 39(3): 249-258, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32525818

RESUMO

Nitric oxide is known as relaxing factor because it acts as a vasodilator, increases blood flow, and inhibits platelet aggregation and adhesion, on the other hand nitric oxide can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. As the complete mechanism of myricetin and its cardiovascular benefits is not completely understood, the aim of this study was to investigate the antihypertensive activity of myricetin in human umbilical vein endothelial cell (HUVEC). Angiotensin converting enzyme (ACE) activity, nitric oxide production, reactive oxygen species (ROS) scavenger activity, cellular calcium concentration, and endothelial nitric oxide synthase (eNOS) activity and protein expression was investigated in HUVEC treated with different concentration of myricetin (1-60 µM). Myricetin increased nitric oxide production in HUVEC through decreased ROS levels and increased nitric oxide production and eNOS activation. Activation of eNOS enzyme was achieved by an increase of cellular calcium concentration. At the same examined concentration of myricetin, the activity of ACE was significantly inhibited. These findings indicate that myricetin may be helpful for lowering blood pressure; this could be achieved through dietary intervention or by the production of new antihypertensive treatments from a natural product.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Óxido Nítrico/biossíntese , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III , Peptidil Dipeptidase A/metabolismo
2.
PLoS Biol ; 18(6): e3000722, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569301

RESUMO

Inflammation and infection can trigger local tissue Na+ accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (MΦs) and their antimicrobial activity. Enhanced Na+-driven MΦ function requires the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5), which augments nitric oxide (NO) production and contributes to increased autophagy. However, the mechanism of Na+ sensing in MΦs remained unclear. High extracellular Na+ levels (high salt [HS]) trigger a substantial Na+ influx and Ca2+ loss. Here, we show that the Na+/Ca2+ exchanger 1 (NCX1, also known as solute carrier family 8 member A1 [SLC8A1]) plays a critical role in HS-triggered Na+ influx, concomitant Ca2+ efflux, and subsequent augmented NFAT5 accumulation. Moreover, interfering with NCX1 activity impairs HS-boosted inflammatory signaling, infection-triggered autolysosome formation, and subsequent antibacterial activity. Taken together, this demonstrates that NCX1 is able to sense Na+ and is required for amplifying inflammatory and antimicrobial MΦ responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate MΦ function.


Assuntos
Macrófagos/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Sódio/metabolismo , Processamento Alternativo/genética , Animais , Cálcio/metabolismo , Espaço Extracelular/metabolismo , Inativação Gênica/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Íons , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7 , Cloreto de Sódio/farmacologia
3.
Food Chem ; 330: 127257, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535321

RESUMO

Huangshui (HS), the by-product of Chinese Baijiu, has attracted considerable attention due to its nutrient and microbial composition; however, none of the studies has explored the polysaccharides in HS yet. Here, from HS, we isolated a novel polysaccharide, HSP-3, with an average molecular weight of 26.40 kDa. The structure was elucidated based on monosaccharide composition and methylation analysis, NMR, FT-IR, and AFM analysis. It is mainly composed of mannose (46.6%), galactose (17.3%), arabinose (11.2%), glucose (10.5%), xylose (8.2%), fucose (5.2%), and rhamnose (1.0%). The backbone of HSP-3 was made up of â†’ 2)-ß-d-Manp-(1 â†’ 2,6)-ß-d-Manp-(1 â†’ 6)-ß-d-Galp-(1 â†’ 3,6)-ß-d-Galp-(1 â†’ 4)-α-l-Rhap-(1 â†’ 3,4)-α-l-Rhap-(1 â†’ . Moreover, stimulation of the production of ROS, NO, TNF-α and IL-6, upregulation of the mRNA and protein expression levels of TNF-α and IL-6 in THP-1 cells, and enhanced the pinocytic and phagocytic capacities of THP-1 cells exhibited significant immunomodulatory properties of HSP-3. Altogether, this study suggests that HSP-3 could be used as an active component in functional foods.


Assuntos
Imunossupressores/farmacologia , Interleucina-6/metabolismo , Óxido Nítrico/biossíntese , Polissacarídeos/farmacologia , Rios/química , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Imunossupressores/química , Peso Molecular , Polissacarídeos/química , Células THP-1
4.
Int J Nanomedicine ; 15: 2647-2658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368046

RESUMO

Purpose: Myocardial ischemia-reperfusion injury primarily causes myocardial infarction (MI), which is manifested by cell death. Angiogenesis is essential for repair and regeneration in cardiac tissue after MI. In this study, we aimed to investigate the effect of exosomes derived from the serum of MI patients in angiogenesis and its related mechanism. Patients and Methods: Exosomes, isolated from serum, were collected from MI (MI-exosome) and control (Con-exosome) patients. After coculturing with human umbilical vein endothelial cells, MI-exosome promoted cell proliferation, migration, and tube formation. Results: The results revealed that the production and release of MI-exosome were associated with cardiomyocytes. Moreover, microarray assays demonstrated that miRNA-143 was significantly decreased in MI-exosome. Meanwhile, the overexpression and knockdown of miRNA-143 could inhibit and enhance angiogenesis, respectively. Furthermore, the effect of exosomal miRNA-143 on angiogenesis was mediated by its targeting gene, insulin-like growth factor 1 receptor (IGF-IR), and was associated with the production of nitric oxide (NO). Conclusion: Taken together, exosomes derived from the serum of patients with MI promoted angiogenesis through the IGF-IR/NO signaling pathway. The results provide novel understanding of the function of exosomes in MI.


Assuntos
Vasos Coronários/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/sangue , Neovascularização Fisiológica , Receptor IGF Tipo 1/metabolismo , Animais , Linhagem Celular , Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Óxido Nítrico/biossíntese , Transdução de Sinais
5.
Chem Biol Interact ; 325: 109088, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360554

RESUMO

Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging people. The activation of chondrocytes and their dysregulation are closely related to the pathogenesis of OA. GPR55 is an unique orphan G-receptor which binds to cannabinoids. In this study, we explored the role of GPR55 in advanced glycation end productions (AGEs)- induced chondrocytes activation in cultured cells. We showed that AGEs dose dependently induced GPR55 expression in ATDC5 chondrocytes. The blockage of GPR55 by its newly discovered antagonist-CID16020046 mitigated AGEs- induced increase in cellular ROS and decrease in antioxidant NRF2. Moreover, CID16020046 showed a dose-response suppressive effect on AGEs- induced expression of the major inflammatory mediators, including COX-2 and iNOS, and the production of NO and PGE2. CID16020046 also dose responsively inhibited AGEs- induced key effectors of cartilage degradation such as MMP-3 and MMP-13. In consequence, CID16020046 showed robust inhibition on AGEs- induced type II collagen degradation. Mechanistically, our data demonstrated that CID16020046 mediated GPR55 blockage ameliorated AGEs- induced NF-κB activation as revealed by its inhibition on IκBα, nuclear p65 translocation and NF-κB promoter activity. Collectively, our study demonstrates that GPR55 signaling mediates AGEs- induced chondrocyte activation, and the targeted blockage of GPR55 pathway could be therapeutic choice in the treatment of osteoarthritis.


Assuntos
Compostos Azabicíclicos/farmacologia , Benzoatos/farmacologia , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Receptores de Canabinoides/metabolismo , Linhagem Celular , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Proteólise/efeitos dos fármacos
6.
Mem Inst Oswaldo Cruz ; 115: e190408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321156

RESUMO

BACKGROUND: The mechanism of resistance to SbIII in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES: In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (SbIII)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS: Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS: The phagocytic capacity and intracellular NO production by classical (CD14++CD16-) and proinflammatory (CD14++CD16+) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(ß1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the SbIII-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS: Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.


Assuntos
Antimônio/farmacologia , Antiprotozoários/farmacologia , Leishmania braziliensis/imunologia , Leishmania infantum/imunologia , Monócitos/parasitologia , Óxido Nítrico/biossíntese , Fagocitose/imunologia , Adulto , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Humanos , Imunidade Inata , Leishmania braziliensis/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Masculino , Monócitos/imunologia , Adulto Jovem
7.
Metabolism ; 107: 154226, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32277945

RESUMO

BACKGROUND: Aberrant endothelial function is a major contributing factor in cardiovascular disease. Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. We hypothesized that the microRNA miR-652-3p negatively regulates endothelial ISL1 expression and that dyslipidemia-induced miR-652-3p upregulation induces aberrant endothelial functioning via ISL1 downregulation. METHODS: Various in vitro experiments were conducted in human umbilical vein endothelial cells (HUVECs). Luciferase assays were performed in HEK293 cells. We constructed a high-fat diet (HFD) Apoe-/- murine model of dyslipidemia and a rat model of low-density lipoprotein (LDL)-induced dyslipidemia to conduct in vivo and ex vivo experiments. RESULTS: Luciferase assays confirmed miR-652-3p's targeting of the ISL1 3'-untranslated region (3'-UTR). Simvastatin blocked oxidized LDL (ox-LDL)-induced increases in miR-652-3p and ox-LDL-induced decreases in ISL1 protein expression, endothelial NO synthase (eNOS) activation, and NO production. Simvastatin's effects were abrogated by miR-652-3p overexpression and phenocopied by miR-652-3p inhibition. The dyslipidemic mouse model exhibited increased miR-652-3p and decreased ISL1 protein levels in the endothelium, effects opposed by simvastatin or miR-652-3p inhibition. The impact of simvastatin in vivo was abolished by overexpressing miR-652-3p or knocking-down ISL1. The rat model of dyslipidemia exhibited a similar pattern of miR-652-3p upregulation, attenuated ISL1 protein levels, decreased eNOS activation, and decreased NO production, effects mitigated by simvastatin. CONCLUSIONS: Dyslipidemia upregulates endothelial miR-652-3p, which decreases ISL1 protein levels, eNOS activation, and NO production. Simvastatin therapy lowers endothelial miR-652-3p expression to protect endothelial function under dyslipidemic conditions.


Assuntos
Dislipidemias/patologia , Dislipidemias/prevenção & controle , Endotélio/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Proteínas com Homeodomínio LIM/biossíntese , MicroRNAs/biossíntese , Fatores de Transcrição/biossíntese , Animais , Apolipoproteínas E/genética , Regulação para Baixo/efeitos dos fármacos , Dislipidemias/genética , Ativação Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/efeitos dos fármacos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley
8.
Artigo em Inglês | MEDLINE | ID: mdl-32302942

RESUMO

Involvement of nitrate reductase (NR) and nitric oxide synthase (NOS)-like enzyme in 24-epibrassinolide (EB)-triggered nitric oxide (NO) synthesis to improve iron deficiency (ID) tolerance in strawberry plants was studied. EB was sprayed to strawberry plants every two days for two weeks. Then, the EB-treated plants were pre-treated with inhibitors of NR, tungstate, or NOS, L-NAME for 3 h. During the first three weeks, Fe was supplied as 100 µM EDTA-Fe or FeSO4 to Fe-sufficient or Fe-deficient plants, respectively. Thereafter, plants were subjected for further three weeks to control (100 µM EDTA-Fe) and Fe deficiency (ID; without Fe). ID reduced biomass, chlorophyll, and chlorophyll fluorescence, while increased oxidative stress parameters, ascorbate (AsA), glutathione (GSH), endogenous NO, and the activities of NR, NOS, and antioxidant enzymes. Pre-treatments with EB and EB + SNP improved ID tolerance of strawberry by improving leaf Fe2+, plant growth, and antioxidant enzyme activities, and causing a further elevation in AsA, GSH, NO, NR and NOS. L-NAME application reversed NOS activity, but it did not eliminate NO, however, tungstate application reversed both NR activity and NO synthesis in plants exposed to ID + EB, suggesting that NR is the main contributor of EB-induced NO synthesis to improve ID tolerance in strawberry plants.


Assuntos
Fragaria , Ferro , Nitrato Redutase , Óxido Nítrico , Regulação para Cima , Ácido Ascórbico/metabolismo , Brassinosteroides/farmacologia , Fragaria/efeitos dos fármacos , Fragaria/enzimologia , Fragaria/genética , Regulação da Expressão Gênica de Plantas , Glutationa/metabolismo , Ferro/deficiência , Nitrato Redutase/metabolismo , Óxido Nítrico/biossíntese , Esteroides Heterocíclicos/farmacologia
9.
Curr Pharm Biotechnol ; 21(11): 1070-1078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101118

RESUMO

INTRODUCTION: The plant, Astilboides tabularis (Hemsl.) Engler, is used in Chinese and Korean medicine to regulate blood sugar levels; however, little is known about its precise effects. MATERIALS AND METHODS: In this study, we aimed to measure the composition as well as the antioxidant, and anti-proliferative capacities of A. tabularis. Various extracts were generated using different organic solvents, and in vitro antioxidant activities were evaluated using DPPH free radical-scavenging and reducing power assays. The extracts were also evaluated based on their ability to inhibit lipopolysaccharide (LPS)-induced Nitric Oxide (NO) production in RAW 264.7 cells. RESULTS: Research shows that the A. tabularis ethyl acetate (EtOAc) extract showed significant antioxidant activity. Additionally, this extract could inhibit the LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in RAW 264.7 cells, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-1 beta (IL-1ß). Notably, the A. tabularis EtOAc extract also displayed potent cytotoxic effects against MCF-7 and HeLa cancer cell lines, as determined by MTT assays. Lastly, total phenol and flavonoid content was measured for all extracts, and four flavonoid compounds-catechin, kaempferol, quercitrin, and isoquercetin were isolated from the EtOAc extract. Their structures were confirmed using mass spectrometry and nuclear magnetic resonance, and these isolated compounds were found to display potent DPPH free radical-scavenging activity. CONCLUSION: Thus, our data suggest that phenolic compounds in A. tabularis extracts promote antioxidant activity, and furthermore, these extracts show numerous features that indicate potential for therapeutic development.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Saxifragaceae/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/química , Células HeLa , Humanos , Lipopolissacarídeos/farmacologia , Células MCF-7 , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polifenóis/química , Polifenóis/isolamento & purificação , Células RAW 264.7
10.
J Microbiol Biotechnol ; 30(3): 333-340, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-31893612

RESUMO

Macrophages are the cells of the first-line defense system, which protect the body from foreign invaders such as bacteria. However, Gram-negative bacteria have always been the major challenge for macrophages due to the presence of lipopolysaccharides on their outer cell membrane. In the present study, we evaluated the effect of phloretin, a flavonoid commonly found in apple, on the protection of macrophages from Escherichia coli infection. RAW 264.7 cells infected with standard E. coli, or virulent E. coli K1 strain were treated with phloretin in a dose-dependent manner to examine its efficacy in protection of macrophages. Our results revealed that phloretin treatment reduced the production of nitric oxide (NO) and generation of reactive oxygen species along with reducing the secretion of proinflammatory cytokines induced by the E. coli and E. coli K1 strains in a concentration-dependent manner. Additionally, treatment of phloretin downregulated the expression of E. coli-induced major inflammatory markers i.e. cyclooxygenase-2 (COX-2) and hemeoxygenase-1 (HO-1), in a concentration dependent manner. Moreover, the TLR4-mediated NF-κB pathway was activated in E. coli-infected macrophages but was potentially downregulated by phloretin at the transcriptional and translational levels. Collectively, our data suggest that phloretin treatment protects macrophages from infection of virulent E. coli K1 strain by downregulating the TLR4-mediated signaling pathway and inhibiting NO and cytokine production, eventually protecting macrophages from E. coli-induced inflammation.


Assuntos
Escherichia coli , Macrófagos/efeitos dos fármacos , Floretina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Inflamação , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
11.
J Microbiol Biotechnol ; 30(3): 352-358, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-31893613

RESUMO

In this study we investigated the immune effects of oral administration of anionic macromolecules extracted from Codium fragile (CFAM) and red ginseng extract mixture on the peritoneal macrophage cells in immune-suppressed mice. Cyclophosphamide (CY) induces the immune-suppressed condition. CY-treated mice were orally fed with different concentrations of CFAM supplemented with red ginseng extract and the peritoneal macrophages collected. CY treatment significantly decreased the immune activities of peritoneal macrophages, compared to the normal mice. The administration of CFAM mixed with red ginseng extract significantly boosted the viability of macrophage cells and nitric oxide production of peritoneal macrophages. Further, the oral administration of CFAM mixed with red ginseng extract up-regulated the expression of iNOS, COX-2, and TLR-4 as well as cytokines such as IL-1ß, IL-6, TNF-α, and IFN-γ more than the red ginseng-treated group. This study showed that CFAM enhanced the immune activity of red ginseng extract in the peritoneal macrophage cells of immune-suppressed mice. Furthermore, CFAM might be used as a co-stimulant of red ginseng extract through the regulation of macrophage cells for the enhancement of human health and immunity.


Assuntos
Imunossupressores/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Panax/química , Extratos Vegetais/farmacologia , Animais , Ânions/química , Regulação da Expressão Gênica , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Fagócitos , Extratos Vegetais/química
12.
Anticancer Res ; 40(1): 565-572, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892613

RESUMO

BACKGROUND/AIM: To assess the effectiveness of three UV emitting lamps on the cutaneous production of vitamin D3, a marker of DNA damage and nitric oxide production in human skin. MATERIALS AND METHODS: Human skin samples (skin types II, III and IV) obtained from surgery were exposed to three different UV emitting lamps for varying times and then extracted and chromatographed to determine the vitamin D3 content. The skin samples exposed to the 3 UV emitting lamps were also evaluated for 8-hydroxy-2'-deoxyguanosine (a marker of DNA damage) and nitric oxide production. RESULTS: It was observed that the spectral output of the 3 lamps had different effects on the cutaneous production of vitamin D3, 8-hydroxy-2'-deoxyguanosine and nitric oxide production. One lamp demonstrated optimal production of vitamin D3 with the least amount of DNA damage and intermediate production of nitric oxide suggesting that it could be developed into a device for treating vitamin D deficiency. CONCLUSION: The spectral output of the experimental UVB emitting lamps significantly influenced the cutaneous production of vitamin D3 8-hydroxy-2'-deoxyguanosine and nitric oxide.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/biossíntese , Colecalciferol/biossíntese , Óxido Nítrico/biossíntese , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Relação Dose-Resposta à Radiação , Eritema/etiologia , Humanos
13.
Food Chem ; 315: 126266, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32000083

RESUMO

Flaxseeds are widely consumed for their desirable sensory attributes and health benefits. We focused on enhancing the sustainability and economic potential of flaxseeds by characterizing functional attributes of polysaccharides isolated from flaxseed hull residues. In particular, antioxidant and immune-stimulatory polysaccharides were isolated and purified from flaxseed hull. Infrared spectroscopy was used to identify the key functional groups. The polysaccharides were composed of mannose, rhamnose, galactose, glucose, galactose, xylose, arabinose, and fucose. In vitro studies showed certain flaxseed hull polysaccharide fractions exhibited strong antioxidant activities, increased nitric oxide levels, and enhanced the production of cytokines (TNF-α and IL-6). In the presence of 200 µg/mL of one of these fractions, the levels of p-ERK, p-JNK, and p-p38 increased significantly by 1.8-, 9.0-, and 6.7-fold. These polysaccharide fractions may exhibit their immune-regulatory properties partly by modulating the MAPK pathway. The flaxseed hull polysaccharides identified have potential application as natural antioxidants and immune-enhancing nutraceuticals.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antioxidantes/farmacologia , Linho/química , Polissacarídeos/análise , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/química , Animais , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Citocinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Óxido Nítrico/biossíntese , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade
14.
Carbohydr Polym ; 232: 115804, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952602

RESUMO

In this present study, the structure and immunomodulatory activity of a novel polysaccharide (WSRP-1b) from Kushui rose (Rosa setate x Rosa rugosa) waste were investigated. Structure characterization demonstrated that WSRP-1b had a weight-average molecular weight of 1.11 × 104 Da and consisted of glucose (42.6 %), mannose (21.4 %), arabinose (9.9 %), xylose (2.2 %), and galactose (23.9 %). Its backbone was composed of 1, 4-linked α-Glcp, 1, 4-linked ß-Glcp, and 1, 4-linked ß-Manp, with branches of 1, 4-linked α-Glcp and 1, 4-linked ß-Manp substituted at C-6 by 1, 6-linked ß-Galp. The branches mainly contained 1, 5-linked Araf, terminal arabinose and terminal glucose. Bioactivity assays showed that WSRP-1b had immunomodulatory activity by enhancing phagocytosis of macrophages, increasing production of ROS, NO, cytokines (IL-6, TNF-α), and activating NF-κB signaling pathway. These results suggested that it could be developed as a potential and safe immunomodulatory agent in fields of pharmacological or functional foods.


Assuntos
Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Rosa/química , Configuração de Carboidratos , Citocinas/biossíntese , Humanos , Fatores Imunológicos/química , Macrófagos/metabolismo , NF-kappa B/imunologia , Óxido Nítrico/biossíntese , Polissacarídeos/química , Espécies Reativas de Oxigênio/metabolismo
16.
Arch Biochem Biophys ; 679: 108187, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706880

RESUMO

Macrophages play a pivotal role in the defense response against harmful pathogens and stimuli by releasing various pro-inflammatory mediators. However, overproduction of pro-inflammatory mediators will do harm to the organism and cause inflammation-associated diseases. Omentin-1, which is a newly discovered adipokine, is specifically expressed in omental adipose tissue. Recent studies have found correlations between omentin-1 and insulin resistance, diabetes, obesity, inflammation, atherosclerosis, bone metabolism, and tumor cell proliferation. Some studies have shown that the association between omentin-1, insulin resistance, and inflammation might suggest that omentin-1 plays an important role in chronic inflammatory diseases. In this study, we found that omentin-1 inhibited LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in macrophages. Furthermore, omentin-1 inhibited activation of the NF-κB pathway by suppressing both nuclear p65 accumulation and transfected NFκB promoter activity. Importantly, omentin-1 increased nuclear translocation of Nrf2. Our findings demonstrate that omentin-1 exerts anti-inflammatory effects on LPS-induced macrophages and has potential implication in the treatment of inflammation-associated diseases.


Assuntos
Lectinas/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Células U937
17.
Chem Biodivers ; 17(1): e1900683, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797569
18.
Int J Food Microbiol ; 315: 108419, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734616

RESUMO

The effects of glucose and sucrose on the gene expression of nitric oxide synthase (NOS) in Staphylococcus vitulinus and colour formation in dry sausages were investigated. The results showed that sucrose addition promoted nitric oxide (NO) production in media when compared with glucose. In addition, sucrose could up-regulate nos (encoding NOS) and katA (encoding catalase KatA) gene expression by enhancing oxidative stress levels. In the sausages inoculated with S. vitulinus, a*-values (indicating redness) of the sausages with added sucrose were higher than those of samples with added glucose (P < 0.05) but did not differ from those in the nitrite treatment group (P > 0.05). The UV-vis spectra results showed that nitrosylmyoglobin (NO-Mb) was formed in the sausages with either S. vitulinus or nitrite added. In the S. vitulinus-inoculated sausages, sucrose addition led to a higher NO-Mb content than that after glucose addition, which was attributed to up-regulation of the nos gene. This study provides a potential method to enhance NO yield in S. vitulinus and colour formation in dry sausages without nitrite addition.


Assuntos
Catalase/biossíntese , Glucose/metabolismo , Óxido Nítrico Sintase/biossíntese , Staphylococcus/metabolismo , Sacarose/metabolismo , Animais , Catalase/genética , Cor , Produtos da Carne/análise , Mioglobina/biossíntese , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/genética , Nitritos/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Staphylococcus/enzimologia , Staphylococcus/genética , Ativação Transcricional , Regulação para Cima
19.
Phytochemistry ; 170: 112191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31731236

RESUMO

Seven undescribed polyketides javanicols A-E, 5-epi-citreoviridin and 5-epi-isocitreoviridin, together with five known compounds, were isolated from the endolichenic fungus Eupenicillium javanicum. The structures of these polyketides were determined by means of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR shift calculations. These compounds were evaluated for potential anti-inflammatory activity against LPS-activated RAW 264.7 cells. Javanicol E and (+)-terrein displayed moderate inhibitory effects on NO production, with IC50 values of 17.00 and 13.46 µM, respectively.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Eupenicillium/química , Óxido Nítrico/antagonistas & inibidores , Policetídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Compostos Fitoquímicos , Policetídeos/química , Policetídeos/isolamento & purificação , Células RAW 264.7
20.
Phytochemistry ; 170: 112186, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31731240

RESUMO

Chemical investigation of the traditional Chinese medicine, Murraya kwangsiensis, led to the isolation of 16 undescribed biscarbazole alkaloids, kwangsines A-M, two undescribed natural products, (+/-)-bispyrayafoline C, and 19 known monomeric analogues. (±)-Bispyrayafoline C and (±)-kwangsines A-C are four pairs of biscarbazole atropisomers, and they were separated by chiral HPLC to obtain the optically pure compounds. The structures of the undescribed compounds were elucidated on the basis of HRESIMS and NMR data analysis. Their absolute configurations were assigned via comparison of the specific rotation, ECD exciton coupling method, as well as comparison of experimental and calculated ECD data. A compound showed significant inhibition on NO production in lipopolysaccharide-stimulated BV-2 microglial cells, and four compounds exhibited moderate cytotoxicities against HepG2 cells, with IC50 values less than 20 µM.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carbazóis/farmacologia , Murraya/química , Compostos Fitoquímicos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Carbazóis/química , Carbazóis/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Relação Estrutura-Atividade
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