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1.
Chem Pharm Bull (Tokyo) ; 67(9): 1006-1014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474723

RESUMO

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.


Assuntos
Ácido Clorogênico/química , Óxido Nítrico/metabolismo , Ácido Salicílico/química , Células A549 , Animais , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , PPAR gama/química , PPAR gama/metabolismo , Estrutura Terciária de Proteína , Células RAW 264.7
2.
Chem Biol Interact ; 313: 108821, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525342

RESUMO

Decrease in the bioavailability of vasoactive nitric oxide (NO), derived from the endothelial nitric oxide synthase (NOS3), underlines vascular endothelial damage. Our expanding knowledge on mature red blood cells (RBCs) makes it supposable that RBCs might contribute to vascular function and integrity via their active NO synthetizing system (RBC-NOS3). This "rescue" mechanism of RBCs could be especially important during pregnancy with smoking habit, when smoking acts as an additional stressor and causes active change in the redox status. In this study RBC populations of 82 non-smoking (RBC-NS) and 75 smoking (RBC-S) pregnant women were examined. Morphological variants were followed by confocal microscopy and quantified by a microscopy based intelligent analysis software. Fluorescence activated cell sorting was used to examine the translational and posttranslational regulation of RBC-NOS, Arginase-1 and the formation of the major product of lipid peroxidation, 4-hydroxy-2-nonenal. To survey the rheological parameters of RBCs like elasticity and plasticity atomic force microscopy-based measurement was applied. Significant morphological and functional differences of RBCs were found between the non-smoking and smoking groups. The phenotypic variations in RBC-S population, even the characteristic biconcave disc-shaped cells, could be connected to impaired NOS3 activation and are compromised in their physiological properties. Membrane lipid studies reveal an elevated lipid oxidation state well paralleled with the changed elastic and plastic activities. These features can form a basic tool in the prenatal health screening conditions; hence the compensatory mechanism of RBC-S population completely fails to sense and rescue the acute oxidative stress conditions.


Assuntos
Arginase/metabolismo , Eritrócitos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Fumar/efeitos adversos , Adulto , Aldeídos/metabolismo , Estudos de Casos e Controles , Morte Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Microscopia de Força Atômica , Gravidez
3.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
4.
Adv Exp Med Biol ; 1155: 717-727, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468442

RESUMO

Endothelial dysfunction is a critical factor in the development of diabetes-mediated cardiovascular complications. Free fatty acids (FFA), such as palmitate, which are elevated in diabetes and obesity, have been shown to mediate endothelial dysfunction, perhaps related to oxidative stress and inflammation. Taurine ameliorates endothelial dysfunction induced by diabetes. However, there has been no reports on the effect of Loliolus beka gray meat extracts, which contain large amounts of taurine. Here, we investigated the protective effect of a hot water extract of Loliolus beka gray meat (LBM), on palmitate-induced cell damage in human umbilical vein endothelial cells (HUVEC). The LBM extract was found to inhibit palmitate-induced cytotoxicity and DNA damage. In addition, the LBM extract reduced the level of reactive oxygen species (ROS) and nitric oxide (NO), as well as pro-inflammatory cytokines in HUVEC. These results suggest that the LBM extract protects against palmitate-induced cytotoxicity in HUVECs. Therefore, potential therapeutic and/or inhibitors of vascular disease may be derived from the LBM extract.


Assuntos
Extratos Celulares/farmacologia , Decapodiformes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Estresse Oxidativo , Animais , Células Cultivadas , Citocinas/metabolismo , Humanos , Carne , Óxido Nítrico/metabolismo , Palmitatos , Espécies Reativas de Oxigênio/metabolismo
5.
Adv Exp Med Biol ; 1155: 729-738, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468443

RESUMO

Gamma ray irradiation causes immune suppression, in which oxidative stress reduces cell viability and damages immune cells. In the present study, we investigated whether Loliolus beka gray meat (LBM), which contains large amounts of taurine, protects against damage of murine splenocytes by oxidative stress. An aqueous extract of LBM (LBMW) was prepared, which contained plentiful levels of taurine. LBMW improved cell viability of gamma ray-irradiated murine splenocytes, an effect that was associated with significant reduction in the production of reactive oxygen species (ROS). We also showed that the production of nitric oxide (NO) and ROS in gamma ray-irradiated zebrafish embryos, as well as the death of the embryos, were diminished by LBMW. These data suggest that the consumption of taurine-rich foods, such as LBM, may be used in the protection of cells against oxidative stress.


Assuntos
Extratos Celulares/farmacologia , Decapodiformes/química , Estresse Oxidativo , Protetores contra Radiação/farmacologia , Taurina/farmacologia , Animais , Células Cultivadas , Raios gama/efeitos adversos , Carne , Camundongos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/citologia
6.
Adv Exp Med Biol ; 1155: 989-999, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468462

RESUMO

In the present study, we investigated the regulation of inflammatory effects by glucose-taurine reduced (G-T-R), a taurine-carbohydrate derivative, on lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The anti-inflammatory action of G-T-R revealed that this derivative markedly inhibited the nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages induced by LPS. Suppression of NO and PGE2 production was involved in the inhibitory action by G-T-R on the inducible nitric oxide synthase and cyclooxygenase-2 proteins expression. G-T-R decreased the production of a variety of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6. Moreover, G-T-R effectively suppressed the nuclear factor-kappa B (NF-κB) activation in LPS-stimulated RAW264.7 macrophages according to evaluation of the molecular inflammatory mechanisms. Thus, we suggest that G-T-R modulates several inflammatory pathways mediated by NF-κB activation, demonstrating its potential or preventing and treating inflammatory conditions.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Taurina/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Glucose/farmacologia , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
7.
Adv Exp Med Biol ; 1155: 1001-1014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468463

RESUMO

Batillaria multiformis (B. multiformis) belong to gastropods. They live generally in the sandpit of the lagoons and the estuaries of the intertidal zone. Most of them are distributed in Korea, Japan and China. In this study, we investigated the anti-inflammatory potential of B. multiformis water extracts (BMW). The results showed that the extracts significantly decreased the production of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-induced RAW 264.7 macrophages. In addition, the extracts suppressed the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner. Further investigation indicated that BMW suppressed phosphorylated c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK) and p38 through the MAPK signaling pathway and influenced the NF-κB signaling pathway by suppressing the IκBα degradation in LPS-induced RAW 264.7 macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Celulares/farmacologia , Gastrópodes/química , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Água
8.
Adv Exp Med Biol ; 1155: 1057-1067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468467

RESUMO

Ribose-taurine (Rib-T) suppressed the generation of inflammatory mediators and cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2) through the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß induced by LPS was effectively blocked by Rib-T. Moreover, the anti-inflammatory actions of Rib-T were involved in its inhibitory effects against the nuclear translocation of nuclear factor-kappa B (NF-κB) p65, and NF-κB DNA-binding activity. These results suggest that the anti-inflammatory action of Rib-T is associated with NF-κB regulation.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Ribose/farmacologia , Taurina/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Inflamação , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA
9.
Adv Exp Med Biol ; 1155: 1069-1081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468468

RESUMO

Scallops belong to cosmopolitan family of bivalves which are found in any oceans. They are one of the most important marine fishery resources in the world. The shell, meat and pearl layer have a high utilization value and a lot of scallops are eaten as food. In this study, we established anti-inflammatory effect of Scallops water extract in lipopolysaccharide (LPS) stimulated RAW 264.7 mononuclear macrophage. Our results indicated that Scallop water extract effectively reduced the synthesis of nitric oxide (NO). In addition, Scallop water extract suppressed the reactive oxygen species (ROS) generation and the expression of IL-6 and TNF-α. Further investigation indicated that anti-inflammatory effect of Scallop water extract via suppressing downregulation of MAPK (JNK, p38 and ERK) and NF-κB signaling.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Celulares/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Pectinidae/química , Animais , Citocinas/metabolismo , Inflamação , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
10.
Bratisl Lek Listy ; 120(8): 569-575, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379179

RESUMO

AIM: Oxidative and nitrosative stress triggers an extensive damage to the tissues. Many herbal and chemical medicines have claimed to possess antioxidant properties. Arbutin exists in some plants such as Pyrus Biossierana Bushe. In this study, an inhibitory effect of arbutin against tert-butyl hydroperoxide induced cytotoxicity was studied using SYTOX TM Green assay for cell viability. The antioxidant effects of arbutin on the generation of malondialdehyde, nitric oxide, activity of oxidative enzyme (Superoxide dismutase and catalyze) and the amount of total thiol in Hep-G2 cells exposed to tert-butyl hydroperoxide were evaluated. METHODS: Hep-G2 cells were cultured in 24-well plates. After 24 hours, the cells were pretreated with the arbutin at different concentrations (0, 100 and 150 µM). 24 hours later, tert-butyl hydroperoxide at different concentrations (0, 150, 200 and 250 µM) was added into the culture media. RESULTS: Arbutin was able to decrease malondialdehyde and nitric oxide concentrations in arbutin treated group in comparison with the control group (p < 0.00001). The catalase and superoxide dismutase enzymes in these cells were significantly decreased in a dose depend manner in the presence of arbutin in comparison with the control group (p < 0.00001). In addition, arbutin was capable of increasing the tert-butyl hydroperoxide mediated reduction in the total thiol amount in comparison with the control group (p < 0.00001.) CONCLUSION: Our investigation demonstrated that tert-butyl hydroperoxide evoked a reactive oxygen and nitrogen species overproduction in Hep-G2 cells. The cells treated with arbutin showed a dose-dependent reduction of tert-butyl hydroperoxide induced reactive oxygen and nitrogen species generation (Fig. 6, Ref. 34).


Assuntos
Antioxidantes/farmacologia , Arbutina/farmacologia , Estresse Nitrosativo , Estresse Oxidativo , Catalase/metabolismo , Células Hep G2 , Humanos , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , terc-Butil Hidroperóxido
11.
BMC Plant Biol ; 19(1): 368, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429706

RESUMO

BACKGROUND: We previously reported the involvement of nitric oxide (NO) and cyclic nucleotide-gated ion channel 6 (CNGC6) in the responses of plants to heat shock (HS) exposure. To elucidate their relationship with heat tolerance in Arabidopsis thaliana, we examined the effects of HS on several groups of seedlings: wild type, cngc6, and cngc6 complementation and overexpression lines. RESULTS: After HS exposure, the level of NO was lower in cngc6 seedlings than in wild-type seedlings but significantly elevated in the transgenic lines depending on CNGC6 expression level. The treatment of seeds with calcium ions (Ca2+) enhanced the NO level in Arabidopsis seedlings under HS conditions, whereas treatment with EGTA (a Ca2+ chelator) reduced it, implicating that CNGC6 stimulates the accumulation of NO depending on an increase in cytosolic Ca2+ ([Ca2+]cyt). This idea was proved by phenotypic observations and thermotolerance testing of transgenic plants overexpressing NIA2 and NOA1, respectively, in a cngc6 background. Western blotting indicated that CNGC6 stimulated the accumulation of HS proteins via NO. CONCLUSION: These data indicate that CNGC6 acts upstream of NO in the HS pathway, which improves our insufficient knowledge of the initiation of plant responses to high temerature.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cálcio/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Óxido Nítrico/metabolismo , Termotolerância , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Canais de Cálcio/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Citosol/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Mutação , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Plântula/genética , Plântula/metabolismo
12.
Fitoterapia ; 137: 104261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284019

RESUMO

Three new sesquilignans, zijusesquilignans A-C (1-3), together with fifteen known compounds (4-18), were isolated from fruits of Ziziphus jujuba var. inermis Rehder (Rhamnaceae). Their chemical structures were established using spectroscopic analyses including 1D- and 2D-NMR, HR-EIMS, and ECD spectra. These compounds were assessed for their inhibitory effects on nitric oxide (NO) production. Of these compounds, 1-3 and 17 displayed inhibitory effects on NO production, with IC50 values ranging from 18.1 to 66.4 µM. Pretreatment with 1 and 17 significantly suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein in cells. Moreover, compounds 1-3, 7, 9, and 17 exhibited cytotoxic activities against three human tumor cell lines, with IC50 values ranging from 8.4 to 44.9 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Frutas/química , Lignanas/farmacologia , Ziziphus/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Humanos , Lignanas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , República da Coreia
13.
Fitoterapia ; 137: 104268, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306720

RESUMO

Solanum nigrum L. (also called as European black nightshade) has been traditionally used as folk medicine and food in some regions. Phytochemical investigations of the immature fruits of S. nigrum yielded five steroidal alkaloid glycosides (1-5), including an unprecedented nor-spirosolane type steroidal alkaloid with a five-membered ring A (1) and two novel spirosolane type steroidal alkaloid glycosides (2, 3), together with eight known phenolic compounds (6-13). Their structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, HR-ESI-MS, and GC analyses. Five steroidal alkaloid glycosides were tested for their potential antiproliferative effects against HL-60, U-937, Jurkat, K562, and HepG2 cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 23.4 ±â€¯2.0 µM, compared to positive control indomethacin (IC50, 47.40 ±â€¯4.50 µM). Compound 4 exhibited significant cytotoxicity against all tested cell lines.


Assuntos
Alcaloides/farmacologia , Glicosídeos/farmacologia , Solanum nigrum/química , Esteroides/farmacologia , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , China , Frutas/química , Glicosídeos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Esteroides/isolamento & purificação
14.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2675-2679, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359676

RESUMO

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) µmol·L-1.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Espectrometria de Massas , Extratos Vegetais/isolamento & purificação , Animais , Cromatografia Líquida , Dracaena , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7
15.
Life Sci ; 232: 116634, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279782

RESUMO

AIM: Here, we evaluated the possible protective effects of oleuropein, the major phenolic constituent in virgin olive oil against glycerol-induced acute kidney injury (AKI) in rats. MAIN METHODS: Twenty-eight Sprague Dawley rats were allocated equally into four groups as follows: control group, oleuropein group (50 mg/kg body weight), AKI group and the oleuropein + AKI group. AKI was induced by injecting 50% glycerol (10 ml/kg body weight) intramuscularly. KEY FINDINGS: Glycerol injection increased the kidney relative weight as well as rhabdomyolysis (RM)- and AKI-related index levels, including the levels of creatine kinase, lactate dehydrogenase, creatinine, urea, and Kim-1 expression. Additionally, alteration in oxidative conditions in renal tissue was recorded, as confirmed by the elevated malondialdehyde and nitric oxide levels and the decreased glutathione content. Concomitantly, the protein and mRNA expression levels of antioxidant enzymes were suppressed. Moreover, Nfe2l2 and Hmox1 mRNA expression was also downregulated. Glycerol triggered inflammatory reactions in renal tissue, as evidenced by the increased pro-inflammatory cytokines and Ccl2 protein and mRNA expression, whereas myeloperoxidase activity was increased. Furthermore, glycerol injection enhanced apoptotic events in renal tissue by increasing the expression of the pro-apoptotic proteins and decreasing that of anti-apoptotic. However, oleuropein administration reversed the molecular, biochemical, and histological alterations resulting from glycerol injection. SIGNIFICANCE: Our data suggest that oleuropein has potential as an alternative therapy to prevent or minimize RM incidence and subsequent development of AKI, possibly due to its potent anti-stress, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Iridoides/farmacologia , Lesão Renal Aguda/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Creatina Quinase/metabolismo , Creatinina/metabolismo , Glutationa/metabolismo , Glicerol/efeitos adversos , Glicerol/farmacologia , Inflamação/metabolismo , Iridoides/metabolismo , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Rabdomiólise/complicações
16.
Ecotoxicol Environ Saf ; 182: 109420, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299472

RESUMO

Mancozeb (MZ), chlorothalonil (CT), and thiophanate methyl (TM) are pesticides commonly used in agriculture due to their efficacy, low acute toxicity to mammals, and short environmental persistence. Although the toxic effects of these pesticides have been previously reported, studies regarding their influence on the immune system are limited. As such, this study focused on the immunomodulatory effect of MZ, CT, and TM pesticides on macrophage cells. RAW 264.7 cells were exposed to a range of concentrations (0.1-100 µg/mL) of these pesticides. CT exposure promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) levels. The MTT and ds-DNA assay results demonstrated that MZ, CT, and TM exposure induced macrophage proliferation. Moreover, MZ, CT, and TM promoted cell cycle arrest at S phase, strongly suggesting macrophage proliferation. The levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ) and caspases (caspase 1, 3, and 8) in macrophages exposed to MZ, CT, and TM pesticides increased, whereas the anti-inflammatory cytokine levels decreased. These results suggest that MZ, CT, and TM exert an immunomodulatory effect on the immune system, inducing macrophage activation and enhancing the inflammatory response.


Assuntos
Praguicidas/toxicidade , Animais , Citocinas/metabolismo , Imunomodulação , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Maneb/toxicidade , Óxido Nítrico/metabolismo , Nitrilos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Tiofanato/toxicidade , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Zineb/toxicidade
17.
Life Sci ; 232: 116662, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323271

RESUMO

AIMS: Vascular endothelial cells act as a selective barrier between circulating blood and vessel wall and play an important role in the occurrence and development of cardiovascular diseases. Astragaloside IV (As-IV) has a protective effect on vascular endothelial cells, but its underlying mechanism remains unclear. This study is aimed at investigating the effect of As-IV on endothelial dysfunction (ED). METHODS: Male Sprague-Dawley (SD) were injected intraperitoneally with 65 mg/kg streptozotocin (STZ) to induce diabetes and then administered orally with As-IV (40, 80 mg/kg) for 8 weeks. Vascular function was evaluated by vascular reactivity in vivo and in vitro. The expression of calpain-1 and eNOS in the aorta of diabetic rats was examined by western blot. NO production was measured using nitrate reductase method. Oxidative stress was determined by measuring SOD, GSH-px and ROS. RESULTS: Our results showed that As-IV administration significantly improved diabetes associated ED in vivo, and both NAC (an antioxidant) and MDL-28170 (calpain-1 inhibitor) significantly attenuated hyperglycemia-induced ED in vitro. Meanwhile, pretreatment with the inhibitor l-NAME nearly abolished vasodilation to ACh in all groups of rats. Furthermore, As-IV increased NO production and the expression of eNOS in the thoracic aorta of diabetic rats. In addition, the levels of ROS were significantly increased, and the activity of SOD and GSH-px were decreased in diabetic rats, while As-IV administration reversed this change in a concentration-dependent manner. CONCLUSION: These results suggest that As-IV improves endothelial dysfunction in thoracic aortas from diabetic rats by reducing oxidative stress and calpain-1.


Assuntos
Calpaína/metabolismo , Endotélio Vascular/efeitos dos fármacos , Hiperglicemia/patologia , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Acetilcisteína/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Biomarcadores/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Diabetes Mellitus Experimental/metabolismo , Dipeptídeos/farmacologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperglicemia/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley , Estreptozocina , Vasodilatação/efeitos dos fármacos
18.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1904-1910, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342720

RESUMO

Xixian Tongshuan Capsules with functions of promoting blood circulation and removing blood stasis,dispelling wind and resolving phlegm,relaxing muscles and activating collaterals,restoring consciousness and inducing resuscitation,has significant effects on main and concurrently symptoms of apoplexy. In this research,908 chemical compounds of Xixian Tongshuan Capsules were collected,and 337 potential targets were discovered by pharmacophore based reverse target identification. Protein interaction network( PIN)was then constructed and Identifying Protein Complex Algorithm( IPCA) was used to obtain the modules of the capsule and analyze the potential action mechanism. According to the research,Xixian Tongshuan Capsules could play a therapeutic role for hyperlipidemia and hypertension by regulating lipid metabolic process and blood pressure,the most direct risk factors of apoplexy. It could be used to treat the cerebral thrombosis and irreversible death of nerve tissue caused by insufficient supply of cerebral tissue blood and oxygen,in a way of regulating blood circulation system and nervous system. Xixian Tongshuan Capsules could also treat stroke-induced inflammation and inflammatory immune response through its regulatory effect on inflammatory immune response. Based on the network analysis,the antiinflammatory activity of Xixian Tongshuan Capsules extracts was investigated by measuring the NO release with Griess reagent method through LPS-induced in vitro inflammation model of RAW264. 7 cells. The results showed that Xixian Tongshuan Capsules extracts inhibited the secretion of NO by LPS-induced RAW264. 7 cells,indicating favorable anti-inflammatory activity. This research illuminates the mechanism of Xixian Tongshuan Capsules based on the PIN analysis at molecular network level,providing a scientific basis for its clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Cápsulas , Humanos , Camundongos , Óxido Nítrico/metabolismo , Mapas de Interação de Proteínas , Células RAW 264.7
19.
J Agric Food Chem ; 67(30): 8312-8318, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31287303

RESUMO

The role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide (NO)-reduced chilling injury (CI) in peach fruit was investigated. The fruit were immersed in sodium nitroprusside (SNP) (NO donor) and neomycin (IP3 inhibitor). Results showed that chilling tolerance was enhanced upon exogenous SNP in postharvest peach fruit. Further, GABA accumulation was stimulated by SNP. The increase in protein expression and activity for enzymes in GABA biosynthesis, including glutamate decarboxylase (GAD), polyamine oxidase (PAO), and amino aldehyde dehydrogenase (AMADH), upon SNP treatment was also observed. Also, the up-regulation of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine d-aminotransferase (OAT) and the down-regulation of proline dehydrogenase (PDH) were induced by SNP treatment, thereby accelating proline production. Additionally, SNP treatment elevated protein expression and activity of alternative oxidase (AOX). The above effects induced upon SNP were partly weakened by neomycin. Therefore, IP3 mediated NO-activated GABA and proline accumulation as well as AOX, thus inducing chilling tolerance in postharvest peach fruit.


Assuntos
Frutas/química , Inositol 1,4,5-Trifosfato/metabolismo , Óxido Nítrico/metabolismo , Prunus persica/metabolismo , Aldeído Desidrogenase/metabolismo , Temperatura Baixa , Armazenamento de Alimentos , Frutas/metabolismo , Glutamato Descarboxilase/metabolismo , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Prunus persica/química , Prunus persica/enzimologia , Ácido gama-Aminobutírico/metabolismo
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 204-208, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257799

RESUMO

OBJECTIVE: To investigate the effects of Xiaotan Huayu Liqiao formula (the Chinese Medicine) on mesenteric artery function in rats exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups as Normoxia, CIH, Formula+CIH and formula group. Rats were exposed to normoxia in the Normoxia and Formula group, or intermittent hypoxia in CIH or Formula+CIH group. Xiaotan Huayu Liqiao formula was given at 24g/kg by intragastric administration before intermittent hypoxia exposure. The pathological changes of mesenteric artery were determined by HE staining, and the relaxation of mesenteric artery (induced by acetylcholine(ACh) and L-arginine(L-Arg)) was recorded by microvascular ring technique. Serums of all rats were collected (0 d and 21 d) and the content of NO was detected by ELISA. The levels of endothelial nitric oxide synthase (eNOS) and p-eNOS were measured by Western blot. RESULTS: Compared with Normoxia group, the mesenteric arterial endothelial injury and media thickening were observed and the relaxation of mesenteric artery was significantly reduced in rats exposed to CIH. The level of NO in serum and the ratio of p-eNOS/eNOS were also decreased in the CIH group. Xiaotan Huayu Liqiao formula administration improved the pathologic changes and dilatation function of mesenteric artery, increased the levels of NO and p-eNOS. Compared with Normoxia group,all the results were not observed significant difference in Formula group. CONCLUSION: Xiaotan Huayu Liqiao formula increased the bioavailability of NO, and ameliorated the CIH induced mesenteric artery function injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hipóxia/patologia , Artérias Mesentéricas/efeitos dos fármacos , Acetilcolina , Animais , Masculino , Artérias Mesentéricas/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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