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1.
Diab Vasc Dis Res ; 17(1): 1479164119896975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32000529

RESUMO

Advanced glycation end-products, especially toxic advanced glycation end-products derived from glyceraldehyde (advanced glycation end-product-2) and glycolaldehyde (advanced glycation end-product-3), are biologically reactive compounds associated with diabetic complications. We previously demonstrated that toxic advanced glycation end-products were internalised into macrophage-like RAW264.7 cells through scavenger receptor-1 class A (CD204). Toxic advanced glycation end-product uptake was inhibited by fucoidan, a sulphated polysaccharide and antagonistic ligand for scavenger receptors, suggesting that sulphated polysaccharides are emerging candidates for treatment of advanced glycation end-product-related diseases. In this study, we compared the effects of six types of sulphated and non-sulphated polysaccharides on toxic advanced glycation end-product uptake in RAW264.7 cells. Fucoidan, carrageenan and dextran sulphate attenuated toxic advanced glycation end-product uptake. Fucoidan and carrageenan inhibited advanced glycation end-product-2-induced upregulation of SR-A, while advanced glycation end-product-3-induced upregulation of scavenger receptor-1 class A was only suppressed by fucoidan. Dextran sulphate did not affect scavenger receptor-1 class A levels in toxic advanced glycation end-product-treated cells. Chondroitin sulphate, heparin and hyaluronic acid failed to attenuate toxic advanced glycation end-product uptake. Heparin and hyaluronic acid had no effect on scavenger receptor-1 class A levels, while chondroitin sulphate inhibited advanced glycation end-product-3-induced upregulation of scavenger receptor-1 class A. Taken together, fucoidan and carrageenan, but not the other sulphated polysaccharides examined, had inhibitory activities on toxic advanced glycation end-product uptake and toxic advanced glycation end-product-induced upregulation of scavenger receptor-1 class A, possibly because of structural differences among sulphated polysaccharides.


Assuntos
Carragenina/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Receptores Depuradores Classe A/antagonistas & inibidores , Animais , Transporte Biológico , Sulfatos de Condroitina/farmacologia , Sulfato de Dextrana/farmacologia , Heparina/farmacologia , Ácido Hialurônico/farmacologia , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Receptores Depuradores Classe A/metabolismo
2.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505754

RESUMO

Novel derivatives of some non steroidal anti-inflammatory drugs, as well as of the antioxidants α-lipoic acid, trolox and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid with lorazepam were synthesised by a straightforward method at satisfactory to high yields (40%-93%). All the tested derivatives strongly decreased lipidemic indices in rat plasma after Triton induced hyperlipidaemia. They also reduced acute inflammation and a number of them demonstrated lipoxygenase inhibitory activity. Those compounds acquiring antioxidant moiety were inhibitors of lipid peroxidation and radical scavengers. Therefore, the synthesised compounds may add to the current knowledge about multifunctional agents acting against various disorders implicating inflammation, dyslipidaemia and oxidative stress.


Assuntos
Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Lorazepam/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Acrilatos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Carragenina/química , Carragenina/farmacologia , Cromanos/química , Cromanos/farmacologia , Humanos , Hiperlipidemias/patologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidores de Lipoxigenase/farmacologia , Lorazepam/análogos & derivados , Ratos , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacologia
3.
Complement Ther Med ; 45: 254-261, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331571

RESUMO

PURPOSE: The objective of the present study was to evaluate the systemic anti-inflammatory activity of the hydroalcoholic extract of the leaves of Licania rigida Benth (EHFLR) on models of systemic inflammation in mice. METHODS: The quantitative chemical profiles of phenolic acids and flavonoids were performed by High-Performance Liquid Chromatography (HPLC). Systemic anti-inflammatory activity was determined from carrageenan and dextran-induced paw edema models and the animals were orally treated (p.o.) with EHFLR at doses of 25, 50, 100 mg/kg, indomethacin (10 mg/kg) for carrageenan-induced paw edema and promethazine (6 mg/kg) for dextran-induced paw edema. The possible mechanisms involved in the anti-inflammatory action of the extract were evaluated by the paw edema models induced by histamine and arachidonic acid, and by the model of carrageenan-induced peritonitis, where vascular permeability and leukocyte migration to the peritoneal cavity were evaluated. RESULTS: The results of the HPLC identified the presence of phenolic acids and flavonoids, with chlorogenic acid (1.16%) and Caempferol (0.81%) as the main constituents. From the results, it was concluded that the extract has an LD50 ≥5000 mg/kg when administered orally in mice as this dose did not trigger deaths in any of the observed groups. EHFLR (25 mg/kg) showed a significant antiderematogenic effect on histamine and arachidonic acid-induced paw edema at the third hour of the tests, with a percentage of inhibition of 46.64% and 18.33%, respectively. The extract (25 mg/kg, p.o.) also significantly reduced vascular permeability and leukocyte migration in the peritoneal cavity. CONCLUSIONS: It is concluded that EHFLR exerts a systemic anti-inflammatory action, which seems to depend, at least in part, on the inhibition of arachidonic acid metabolism and the action of vasoactive amines. In addition, the extract reduced the leukocyte migration in the peritoneal cavity, indicating that its action may be linked to the inhibition of pro-inflammatory cytokines.


Assuntos
Anti-Inflamatórios/farmacologia , Chrysobalanaceae/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Flavonoides/farmacologia , Hidroxibenzoatos/farmacologia , Masculino , Camundongos , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Fitoterapia/métodos , Folhas de Planta/química
4.
Mar Drugs ; 17(6)2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31234532

RESUMO

CONTEXT: Seaweed metabolites (fucoidans, carrageenans, ulvans, lectins, and polyphenols) are biologically active compounds that target proteins or genes of the influenza virus and host components that are necessary for replication and reproduction of the virus. OBJECTIVE: This review gathers the information available in the literature regarding to the useful properties of seaweeds metabolites as potential agents for the prevention and therapy of influenza infection. MATERIALS AND METHODS: The sources of scientific literature were found in various electronic databases (i.e., PubMed, Web of Science, and ScienceDirect) and library search. The retrospective search depth is 25 years. RESULTS: Influenza is a serious medical and social problem for humanity. Recently developed drugs are quite effective against currently circulating influenza virus strains, but their use can lead to the selection of resistant viral strains. In this regard, new therapeutic approaches and drugs with a broad spectrum of activity are needed. Metabolites of seaweeds fulfill these requirements. This review presents the results of in vitro and in vivo experimental and clinical studies about the effectiveness of these compounds in combating influenza infection and explains the necessity of their use as a potential basis for the creation of new drugs with a broad spectrum of activity.


Assuntos
Antivirais/metabolismo , Antivirais/farmacologia , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/prevenção & controle , Alga Marinha/metabolismo , Animais , Carragenina/metabolismo , Carragenina/farmacologia , Humanos , Polifenóis/metabolismo , Polifenóis/farmacologia , Estudos Retrospectivos
5.
J Diabetes Res ; 2019: 9582714, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179345

RESUMO

Exposure to low concentration of the common food additive carrageenan (10 mg/L) for only six days led to glucose intolerance and insulin resistance in the C57BL/6J mouse. Longer exposure produced fasting hyperglycemia but with no increase in weight, in contrast to the HFD. Glucose intolerance was attributable to carrageenan-induced inflammation and to increased expression of GRB10. Both HFD and carrageenan increased p(Ser32)-IκBα and p(Ser307)-IRS1, and the increases were greater following the combined exposure. The effects of carrageenan were inhibited by the combination of the free radical inhibitor Tempol and BCL10 siRNA, which had no impact on the HFD-mediated increase. In contrast, the PKC inhibitor sotrastaurin blocked the HFD-induced increases, without an effect on the carrageenan-mediated effects. HFD had no impact on the expression of GRB10. Both carrageenan and high fat increased hepatic infiltration by F4/80-positive macrophages. Serum galectin-3 and galectin-3 binding to the insulin receptor increased by carrageenan and by HFD. Tyrosine phosphorylation of the insulin receptor declined following either exposure and was further reduced by their combination. Carrageenan reduced the activity of the enzyme N-acetylgalactosamine-4-sulfatase (ARSB; arylsulfatase B), which was unchanged following HFD. Dietary exposure to both high fat and carrageenan can impair insulin signaling through both similar and distinct mechanisms.


Assuntos
Carragenina/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Animais , Proteína 10 de Linfoma CCL de Células B/metabolismo , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Proteína Adaptadora GRB10/metabolismo , Galectina 3/metabolismo , Regulação da Expressão Gênica , Intolerância à Glucose , Células Hep G2 , Humanos , Inflamação , Insulina/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , N-Acetilgalactosamina-4-Sulfatase/metabolismo , Ligação Proteica , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Marcadores de Spin , Triglicerídeos/metabolismo
6.
BMC Plant Biol ; 19(1): 258, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208344

RESUMO

BACKGROUND: It has been previously shown that oligo-carrageenan (OC) kappa increases growth, photosynthesis and activities of enzymes involved in basal and secondary metabolisms in Eucalyptus globulus. However, it is not known whether OC kappa may induce the activation of TOR pathway and the increase in expression of genes encoding proteins involved in photosynthesis and enzymes of basal and secondary metabolisms. RESULTS: E. globulus trees were sprayed on leaves with water (control) or with OC kappa 1 mg mL- 1, once a week, four times in total, and cultivated for 17 additional weeks (21 weeks in total). Treated trees showed a higher level of net photosynthesis than controls, beginning at week 3, a higher height, beginning at week 9, and those differences remained until week 21. In addition, treated trees showed an increase in the level of glucose beginning at week 1, trehalose at weeks 1-3, and in TOR-P level at week 1-2. On the other hand, transcripts encoding proteins involved in photosynthesis, and enzymes involved in glucose accumulation, C, N and S assimilation, and synthesis of secondary metabolites began at weeks 3-4 and with additional peaks at weeks 5-6, 8-11,13-14 and 17-19. Thus, OC kappa induced initial increases in glucose, trehalose and TOR-P levels that were followed by oscillatory increases in the level of transcripts coding for proteins involved in photosynthesis, and in basal and secondary metabolisms suggesting that initial increases in glucose, trehalose and TOR-P may trigger activation of gene expression. CONCLUSIONS: The stimulation of growth induced by OC kappa in E. globulus trees is due, at least in part, to activation of TOR pathway and the increase in expression of genes encoding proteins involved in photosynthesis and enzymes of basal metabolism.


Assuntos
Carragenina/farmacologia , Fotossíntese/efeitos dos fármacos , Metabolismo Basal/genética , Eucalyptus/genética , Eucalyptus/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glucose/metabolismo , Fotossíntese/genética , Proteínas de Plantas/metabolismo , Metabolismo Secundário/efeitos dos fármacos , Metabolismo Secundário/genética , Serina-Treonina Quinases TOR/metabolismo , Trealose/metabolismo
7.
Nutrients ; 11(5)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117266

RESUMO

Kappaphycus is a commercially important edible red alga widely cultivated for carrageenan production. Here, we aimed to investigate the anti-obesity mechanism of Kappaphycus alvarezii by comparing the effects of whole seaweed (T), extracted native κ-carrageenan (CGN), and the leftover fraction sans-carrageenan (SCGN) supplementations (5%, w/w) on diet-induced obese C57BL/6J mice. A high-fat diet induced both a raised body fat percentage and serum cholesterol level, increased adipocytes size, abnormal levels of adipocytokines, and promoted gut dysbiosis. Our results showed that, overall, both CGN and SCGN were more effective in reversing obesity and related metabolic syndromes to normal levels than T. Furthermore, these findings suggested that CGN- and SCGN-modulated gut dysbiosis induced by a high-fat diet, which may play an influencing role in adiponectin dysregulation. Our data also showed some evidence that CGN and SCGN have distinct effects on selected genes involved in lipid metabolism. In conclusion, both κ-carrageenan and SCGN have novel anti-obesity potential with possible different mechanisms of action.


Assuntos
Fármacos Antiobesidade/farmacologia , Carragenina/farmacologia , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Rodófitas/química , Adipocinas/metabolismo , Animais , Fármacos Antiobesidade/química , Carragenina/química , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Projetos Piloto , Extratos Vegetais/química , Organismos Livres de Patógenos Específicos
8.
Medicina (Kaunas) ; 55(4)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959829

RESUMO

Background and objectives: The clinical use of non-steroidal anti-inflammatory drugs is limited due to high incidence of adverse drug reactions. The pyrrole heterocycle is included in the chemical structure of a number of drugs with various activities and shows relatively good tolerability and safety. The objectives of our study were to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity, of 2-[3-acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid (compound 3g), a novel N-pyrrolylcarboxylic acid structurally similar to celecoxib. Materials and methods: All experiments were performed on 6-week-old male Wistar rats divided into parallel groups (n = 8). Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick, and formalin tests). Criteria for the analgesic effect were increased latency in the paw withdrawal and tail-flick tests and decreased paw licking time in the formalin test compared to animals treated with saline (control). Anti-inflammatory activity was measured using a carrageenan-induced paw edema model; the criterion for anti-inflammatory effect was decreased edema compared to control. Blood samples were obtained after animals were sacrificed to assess possible organ toxicity. Statistical analysis was performed with IBM SPSS 20.0. Results: 2-[3-Acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid had analgesic action against chemical stimulus after single and multiple administration and against thermal stimulus after single administration. Compound 3g significantly suppressed carrageenan-induced paw edema after both single and continuous administration. After continuous administration, hematological tests showed that compound 3g decreased leukocyte and platelet levels and elevated serum creatinine levels. Conclusions: Antinociception with the tested compound is most likely mediated by spinal, peripheral, and anti-inflammatory mechanisms. Possible tolerance of the analgesic action at the spinal level develops after continuous administration. Anti-inflammatory activity is significant and probably the leading cause of antinociception. After multiple administration, compound 3g showed signs of potential nephrotoxicity and antiplatelet activity, as well as suppression of leukocyte levels.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Celecoxib/análogos & derivados , Celecoxib/farmacologia , Avaliação Pré-Clínica de Medicamentos , Indóis/química , Indóis/farmacologia , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Análise de Variância , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Carragenina/administração & dosagem , Carragenina/farmacologia , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Eritrócitos/efeitos dos fármacos , Hemoglobinas/análise , Leucócitos/efeitos dos fármacos , Masculino , Modelos Animais , Medição da Dor , Pirróis/química , Ratos , Ratos Wistar
9.
Inflammopharmacology ; 27(4): 749-760, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30953227

RESUMO

In continuation with our previous studies on osthole, bergapten, a closely related furanocoumarin was investigated for its ameliorative effect on chemically induced neurogenic and inflammatory hyperalgesia and inflammation in mice. Chemical hyperalgesia and inflammation was induced by administration of formalin (intraplantar), acetic acid (intraperitoneal) and carrageenan (intraplantar) to different groups of animals. Pain responses were quantified and median effective dose (ED50) of bergapten was calculated. Lipopolysaccharide challenge was administered to study inflammatory cytokines which were analyzed in plasma using ELISA. The expression of poly ADP-ribose polymerase (PARP), cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) was quantified by immnofluorescence staining. Bergapten was found to ameliorate both neurogenic and inflammatory hyperalgesia precipitated by formalin, acetic acid induced writhing and carrageenan induced paw inflammation with ED50 dose of 2.96 mg/kg. Bergapten also significantly decreased the levels of TNF-α and IL-6 and the expression of PARP, COX-2 and iNOS in the spine. It is concluded that bergapten is an interesting molecule with significant analgesic and anti-inflammatory activity emanating through the modulation of multiple pain mediating pathways.


Assuntos
5-Metoxipsoraleno/farmacologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/metabolismo , Dor Nociceptiva/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Coluna Vertebral/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Carragenina/farmacologia , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Dor Nociceptiva/metabolismo , Coluna Vertebral/metabolismo
10.
Mar Drugs ; 17(3)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818840

RESUMO

In tumor development, the degradation of heparan sulfate (HS) by heparanase (HPSE) is associated with cell-surface and extracellular matrix remodeling as well as the release of HS-bound signaling molecules, allowing cancer cell migration, invasion and angiogenesis. Because of their structural similarity with HS, sulfated polysaccharides are considered a promising source of molecules to control these activities. In this study, we used a depolymerisation method for producing λ-carrageenan oligosaccharides (λ-CO), with progressive desulfation over time. These were then used to investigate the influence of polymeric chain length and degree of sulfation (DS) on their anti-HPSE activity. The effects of these two features on λ-CO anticoagulant properties were also investigated to eliminate a potential limitation on the use of a candidate λ-CO as a chemotherapeutic agent. HPSE inhibition was mainly related to the DS of λ-CO, however this correlation was not complete. On the other hand, both chain length and DS modulated λ-CO activity for factor Xa and thrombin IIa inhibition, two enzymes that are involved in the coagulation cascade, and different mechanisms of inhibition were observed. A λ-carrageenan oligosaccharide of 5.9 KDa was identified as a suitable anticancer candidate because it displayed one of the lowest anticoagulant properties among the λ-CO produced, while showing a remarkable inhibitory effect on MDA-MB-231 breast cancer cell migration.


Assuntos
Anticoagulantes/farmacologia , Antineoplásicos/farmacologia , Carragenina/farmacologia , Glucuronidase/antagonistas & inibidores , Oligossacarídeos/farmacologia , Anticoagulantes/química , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carragenina/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios Enzimáticos , Feminino , Glucuronidase/metabolismo , Heparitina Sulfato/metabolismo , Humanos , Oligossacarídeos/química
11.
Biomed Pharmacother ; 111: 1046-1056, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841418

RESUMO

BACKGROUND: Bothropic venoms cause intense local damage, pain, edema, and myonecrosis. Morus nigra L. (Moraceae) has several uses in folk medicine and can be a promising candidate for the treatment of several inflammatory disorders. HYPOTHESIS/PURPOSE: The present study aims to evaluate the anti-inflammatory and antinociceptive effects of the ethanolic extract of Morus nigra L. (Mn-EtOH) on paw lesions induced by Bothrops jararacussu snake venom (BjcuV) in mice. METHODS: UV-vis absorption of BjcuV was evaluated. A phytochemical study was performed, which led to the isolation and characterization of three compounds. These compounds were identified using spectrometric methods, namely LC-MS and NMR (1D and 2D), followed by the validation of their spectra with the data available in the literature. Further, the flavonoids i.e. rutin and quercetin (chemical markers of M. nigra), Mn-EtOH or Mn-EtOH-encapsulated electrospun fibers of Eudragit L100 (FB/Mn-EtOH), and Mn-EtOH-encapsulated microparticles of Eudragit L100 (MP/Mn-EtOH) were evaluated, in paw edema test induced by BjcuV. RESULTS: UV-vis spectra showed the presence of phospholipases A2 as component of BjcuV. The chemical examination resulted in the isolation of ß-sitosterol, quercetin-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside. Mn-EtOH, FB/Mn-EtOH, MP/Mn-EtOH, rutin, and quercetin reduced the local edema induced by BjcuV. The Mn-EtOH also prevented edema provoked by serotonin and bradykinin. Moreover, it reduced paw edema and peritoneal leukocyte infiltration induced by carrageenan, and decreased the mechanical hypernociception of BjcuV. Mn-EtOH exerted anti-inflammatory and antinociceptive effects, possibly by the inhibition of leukocyte migration and the modulation of serotonin and bradykinin actions. This anti-inflammatory activity was maintained even upon incorporation of the M. nigra extract into the drug delivery systems (i.e., Mn-EtOH-encapsulated FBs and MPs of Eudragit L100). CONCLUSION: These results reinforce the therapeutic potential of M. nigra in the treatment of inflammatory conditions, in addition to, its role as a complementary treatment of snakebites.


Assuntos
Edema/tratamento farmacológico , Moraceae/química , Morus/química , Nociceptividade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Venenos de Serpentes/farmacologia , Animais , Bothrops , Carragenina/farmacologia , Movimento Celular/efeitos dos fármacos , Edema/induzido quimicamente , Feminino , Leucócitos/efeitos dos fármacos , Medicina Tradicional/métodos , Camundongos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
12.
Biomed Pharmacother ; 111: 1187-1203, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841432

RESUMO

BACKGROUND: Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for treating these ailments have not been compared till date. AIM: To ascertain the effect of young and old leaves of VA in managing inflammation, pain and fever. METHODS: Both quantitative and qualitative phytochemical screening of ethanol extracts of young (EthYL) and old (EthOL) leaves of VA were performed. The anti-inflammatory activity of orally administered EthYL and EthOL (50-200 mg/kg) and Diclofenac (10 mg/kg) were evaluated in carrageenan-induced inflammation model in rats. Antipyretic activity of EthYL, EthOL and Aspirin (25 mg/kg) were assessed in the Baker's yeast-induced pyrexia model. Anti-allodynic effect of both extracts were evaluated by inserting inflamed paws of rats in cold water. Antinociceptive property of the extracts were assessed using tail withdrawal and formalin-induced nociception test. Histopathological examination of the paws was performed, in addition to formalin test to understand the possible mechanism of action of the extracts. Negative control rats received 2 ml/kg normal saline in all tests. RESULTS: The amount of flavonoids, alkaloids, tannins, and phenolics were significantly (p < 0.05) higher in EthOL than EthYL, while saponins were significantly higher (p < 0.05) in EthYL than EthOL. The antioxidant ability and total antioxidant capacity were significantly (p < 0.05) higher in EthYL than EthOL. However, this was significantly (p < 0.05) lower than the anti-oxidant activity of Ascorbic acid. A dose-dependent increase in anti-inflammatory, antipyretic and antinociceptive properties were observed in both EthYL and EthOL, similar to the standard drugs. Mast cell degranulation accompanied by vasodilatation and high leukocytosis were observed in the negative control, but were markedly low in extract treated groups. Both extracts mediated their analgesic effect through opioidergic and nitric oxide pathways with EthYL additionally implicating the muscarinic cholinergic system. CONCLUSION: Although both EthYL and EthOL alleviate inflammation, pyrexia and nociception, EthYL of VA was found to be more potent than EthOL.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antipiréticos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Vernonia/química , Animais , Antioxidantes/farmacologia , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Febre/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Fitoterapia/métodos , Ratos , Ratos Sprague-Dawley
13.
Mater Sci Eng C Mater Biol Appl ; 96: 583-590, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30606569

RESUMO

Composite hydrogels were obtained by the entrapment of chitosan, pectin or κ-carrageenan within methacrylate-based hydrogels to improve their swelling and the mechanical properties. The results indicated that the water uptake (WU) of κ-carrageenan and chitosan hydrogels were until 3.5 and 2.2 times higher than the WU of the synthetic hydrogel, respectively. The surface morphologies of the hydrogels showed that the pectin and κ-carrageenan favors the formation of larger and more defined pores. The mechanical properties indicated that the pectin increased slightly the mechanical properties and the κ-carrageenan improves the mechanical properties of the synthetic hydrogel reaching up 400 N of compression load. Therefore, the entrapment of κ-carrageenan within synthetic hydrogels improved both the swelling and the mechanical properties. The biocompatibility of the hydrogels was evaluated with in vitro cytotoxicity assays and the results indicated that they could be considered as candidates for biomedical use.


Assuntos
Carragenina , Quitosana , Hidrogéis , Teste de Materiais , Pectinas , Animais , Carragenina/química , Carragenina/farmacologia , Linhagem Celular , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Pectinas/química , Pectinas/farmacologia
14.
Inflammopharmacology ; 27(3): 603-612, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30680651

RESUMO

Overproduction of inflammatory markers by immune cells, such as macrophages and neutrophils, is one of the main reasons for many inflammatory conditions and inhibiting or suppressing of their production by cell depletion may provide new therapeutic targets or approaches to prevent a variety of inflammatory conditions. In this study, we examined the possible effects of anti-Ly6G-mediated systemic neutrophil depletion and liposome-encapsulated clodronate (LEC)-mediated systemic macrophage depletion on the inflammatory signs (thermal hyperalgesia, mechanical allodynia, oedema and fever) and measured the levels of various inflammation markers (tumour necrosis factor-α (TNF-α), interleukins (IL)-1ß, IL-4, IL-10, macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) and myeloperoxidase (MPO) in paw and spinal cord tissues in carrageenan (CG)-induced hindpaw inflammation model in rats. CG injection into the paw caused inflammation characterized by redness, swelling, heat and pain hypersensitivities. Anti-Ly6G or LEC significantly ameliorated the pain behaviours, and decreased the oedema and fever. Efficacies of anti-Ly6G or LEC on inflammatory responses changed depend on the degree of inhibition in inflammatory markers of inflamed paw or spinal cord. Anti-inflammatory properties of anti-Ly6G or LEC suggest that macrophages and/or neutrophil-mediated inflammatory cascade in inflamed site and spinal cord which can play key roles in inflammatory pain responses. These systemic or peripheral inflammatory mediators may be therapeutic targets in the treatment of many inflammatory conditions and related various diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Biomarcadores/metabolismo , Ácido Clodrônico/farmacologia , Inflamação/tratamento farmacológico , Lipossomos/química , Animais , Carragenina/farmacologia , Ácido Clodrônico/química , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo
15.
Inflammopharmacology ; 27(2): 397-408, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29372359

RESUMO

BACKGROUND: Annona crassiflora Mart., popularly known as "Araticum", is a native tree of the Brazilian Cerrado used in folk medicine for treatment of pain and inflammatory diseases. We proposed to analyze analgesic and anti-inflammatory properties of the filtrate (F1) and the precipitate (F2) of the hydroalcoholic fraction from the leaves of Annona crassiflora Mart. in mice. MATERIALS AND METHODS: Swiss mice were submitted to formalin-induced nociception test and tail-flick reflex test, to assess antinociceptive properties, and to the rota-rod test, for motor performance analyses. To evaluate anti-inflammatory properties, F1 and F2 were orally administered 1 h prior to the intrathoracic injection of carrageenan, zymosan, LPS, CXCL8, or vehicle in Balb/c mice and neutrophil infiltration was evaluated 4 h after injection. RESULTS: F1 and F2 reduced the licking time in the second phase of formalin-induced nociception test, but only F2 showed a dose-dependent response. Neither F1 nor F2 reduced the latency time in the tail-flick reflex test. In addition, motor performance alteration was not observed in F1- or F2-treated mice. F2 treatment significantly inhibited the neutrophilia induced by carrageenan, LPS, or CXCL8, but not zymosan. CONCLUSIONS: The experimental data demonstrated that hydroalcoholic fractions of Annona crassiflora Mart. leaves have remarkable anti-inflammatory and antinociceptive activities.


Assuntos
Analgésicos/farmacologia , Annona/química , Anti-Inflamatórios/farmacologia , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Carragenina/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C
16.
Inflammopharmacology ; 27(1): 157-166, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29946770

RESUMO

OBJECTIVE: The present study aimed to evaluate the anti-inflammatory and analgesic activities of the ginsenoside metabolite compound K (CK) and its mechanisms. METHODS: Mice model of xylene-induced ear swelling and rat model of carrageenan-induced paw swelling were used to evaluate the effect of CK on acute inflammation. The analgesic effect of CK was evaluated on heat-, acetic acid-, and carrageenan-induced hyperalgesia. The levels of prostaglandin E2 (PGE2), cyclooxygenase-1 (COX-1), and COX-2 in carrageenan-induced rat paw swelling and gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA). COX-1 and COX-2 expressions in carrageenan-induced rat paw swelling and gastric mucosa were detected by western blotting. In vitro effect of CK (10-9, 10-8, 10-7, 10-6, 10-5 M) on COX-1 and COX-2 activities was evaluated by measuring the production of 6-keto-PGF1α and PGE2 in rat peritoneal macrophages. RESULTS: CK at doses of 7, 14, 28, 56, 112, and 224 mg/kg alleviated xylene-induced ear oedema, whereas CK at 40, 80, and 160 mg/kg alleviated carrageenan-induced paw oedema. CK at 224 mg/kg showed an analgesic effect against acetic acid-induced pain. CK at 40, 80, and 160 mg/kg significantly increased rat inflammatory pain threshold, but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160 mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the gastric mucosa. CK at 20, 40, 80, and 160 mg/kg decreased COX-2 expression in the paw tissue and gastric mucosa, but exhibited no effect on COX-1 expression or on COX-1 and COX-2 activities. CONCLUSION: CK exerted anti-inflammatory and analgesic effects, possibly by reducing the catalytic synthesis of PGE2 via downregulation of COX-2 expression.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ginsenosídeos/farmacologia , Inflamação/tratamento farmacológico , Animais , Carragenina/farmacologia , Ciclo-Oxigenase 1/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Feminino , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Dor/metabolismo , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Inflammopharmacology ; 27(1): 121-128, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30182184

RESUMO

Dizocilpine is a highly selective and potent non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. It is well known that dizocilpine has different neuroprotective effects in animal models of pain, epilepsy and oedema during trauma. The search for alternative antiinflammatory drugs is ongoing. We investigated the anti-oedematous effects of dizocilpine and the probable mechanism of action in a rat model that mimics local and persistent inflammation without tissue injury or damage. Male Wistar rats were injected with 100 µL of 0.5% carrageenan to the plantar surface of the hind paw. Anti-oedematous activity was assessed in the carrageenan-induced paw inflammatory oedema test with a plethysmometer. To assess possible mechanisms of dizocilpine action, we examined the effects of the selective inhibitor of neuronal [N-ω-propyl-L-arginine hydrochloride (L-NPA)] and inducible [S-methylisothiourea (SMT)] nitric oxide synthase (NOS). Dizocilpine after systemic (0.0005, 0.005 and 0.02 mg/kg, subcutaneous (s.c.)), but not after local peripheral administration, reduced the paw inflammatory oedema. The effect is not dose dependent, and the highest decrease by about 47% at the time of maximally developed oedema was achieved with 0.005 mg/kg. Intraperitoneally (i.p.) administered L-NPA (0.5, 1 and 2 mg/kg) or SMT (0.005, 0.01 and 0.015 mg/kg) before dizocilpine abolished or reduced the anti-oedematous effect of dizocilpine by about 70-85%. An acute single dose of dizocilpine administered before inducing oedema systemically reduced the development of inflammatory oedema. The mechanism of the anti-oedematous effect includes, at least partially, an increase in nitric oxide (NO) production.


Assuntos
Carragenina/farmacologia , Maleato de Dizocilpina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Arginina/metabolismo , Edema/metabolismo , Inflamação/metabolismo , Isotiurônio/análogos & derivados , Isotiurônio/metabolismo , Masculino , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo
18.
J Sci Food Agric ; 99(4): 1812-1819, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30255626

RESUMO

BACKGROUND: Seaweed oligosaccharides are environmentally-friendly natural products and their use for disease control in sustainable agriculture is extremely promising. Enzymatic digestion to prepare seaweed oligosaccharides has drawn considerable interest. However, the study of enzymatically degraded products of carrageenan is still in its infancy compared with that of other hydrocolloids such as agar and alginate. To prepare degraded carrageenan on a commercial scale, it is necessary to select superior producer bacterial strains to improve the yield and thermostability of carrageenases. RESULTS: The carrageenan-degrading bacterium Bacillus sp. HT19 was isolated from sediment of a hot spring in Indonesia, and a κ-carrageenase with high activity was purified from the culture supernatant. The purified enzyme, named Car19, had maximum activity (538 U mg-1 ) at 60 °C and pH 7.0. Notably, the enzyme retained >90% of its initial activity after incubation at 60 °C for 24 h. The Ca2+ obviously improved the thermostability of Car19 at 70 °C. The Km and Vmax values of purified Car19 were 0.061 mg mL-1 and 115.13 U mg-1 , respectively, with κ-carrageenan as substrate. Thin-layer chromatography and electrospray ionization mass-spectrometry analysis of hydrolysates indicated that the enzyme exolytically depolymerized κ-carrageenan to neo-carrabiose. The hydrolysate enhanced the resistance of cucumber to cucumber mosaic virus and increased the activity of antioxidant enzymes in infected plants. CONCLUSION: To our knowledge, Car19 is the most thermostable κ-carrageenase reported so far. Its high optimal reaction temperature and thermostability, and unitary hydrolysate constituent, makes Car19 a promising candidate for the preparation of carrageenan oligosaccharides with plant protection activity. © 2018 Society of Chemical Industry.


Assuntos
Bacillus/enzimologia , Proteínas de Bactérias/química , Glicosídeo Hidrolases/química , Fontes Termais/microbiologia , Oligossacarídeos/metabolismo , Oligossacarídeos/farmacologia , Doenças das Plantas/prevenção & controle , Bacillus/química , Bacillus/genética , Bacillus/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Carragenina/química , Carragenina/metabolismo , Carragenina/farmacologia , Cucumis sativus/virologia , Cucumovirus/efeitos dos fármacos , Cucumovirus/fisiologia , Estabilidade Enzimática , Glicosídeo Hidrolases/isolamento & purificação , Glicosídeo Hidrolases/metabolismo , Temperatura Alta , Cinética , Oligossacarídeos/química , Doenças das Plantas/virologia
19.
Scand J Med Sci Sports ; 29(1): 82-88, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30256459

RESUMO

Interleukin-1 (IL1) is a cytokine that plays a role in inflammation and is a potential contributor to the inflammation present in tendinopathy. Its inhibition may be of use in the treatment of tendinopathy and has been a target for treatment. To evaluate how an IL1-receptor antagonist (IL1-RA) reverses pathologic changes associated with established patellar tendinopathy, we randomized 48 Sprague-Dawley retired breeder rats into three groups having weekly bilateral patellar tendon injections for 6 weeks. The control group received 0.1 mL saline for 6 weeks. The intervention groups were treated with 0.1 mL 2% carrageenan for 4 weeks. Beginning at week three, the IL1-RA group received 0.94 mg of the IL1-RA (2.5 mg/kg) added to the 0.1 mL 2% carrageenan and 0.94 mg of the IL1-RA alone for the final 2 weeks, while the CAR received 0.1 mL saline for the final 2 weeks. Animals were euthanized 6 weeks after initial injection. The CAR group demonstrated significantly (P < 0.05) shorter tendon lengths (7.81 ± 0.44 mm) than the control (8.25 ± 0.58 mm) and IL1-RA (8.34 ± 0.52 mm) group (P < 0.05). Macroscopically, plaque-like formations were reduced and margins of the tendon were more evident in the IL1-RA group compared to the CAR group. CAR group demonstrated significantly greater histopathologic changes (inflammatory cell density, disorganization of collagen, nuclear rounding, and angiogenesis) than the control and IL1-RA group. No significant difference in mechanical properties of the tendon was noted. These findings demonstrate IL1-RA can reduce pathologic changes in the patellar tendon in an established tendonitis model although did not demonstrate a difference in mechanical properties.


Assuntos
Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Ligamento Patelar/patologia , Receptores Tipo I de Interleucina-1/antagonistas & inibidores , Tendinopatia/patologia , Animais , Carragenina/farmacologia , Feminino , Distribuição Aleatória , Ratos Sprague-Dawley
20.
Acta Biomater ; 83: 425-434, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30342285

RESUMO

The combination of kappa-carrageenan (κ-CG) and hydroxyapatite (HA) to generate a bone substitute material has been underexplored to date. Carrageenans (CGs) have remarkable characteristics such as biocompatibility, hydrophilicity, and structural similarities with natural glycosaminoglycans (GAGs), and they have demonstrated the ability to stimulate cellular adhesion and proliferation. Hydroxyapatite nanoparticles have been one of the most investigated materials for bone regeneration due to their excellent biocompatibility, bioactivity and osteoconductivity. In particular, this study presents an approach for the preparation of new bioactive composites of κ-CG/nHA for numerous bone regeneration applications. We performed a set of in vitro experiments to evaluate the influence of the bone substitutes on human osteoblasts. Cell culture studies indicated that all samples tested were cytocompatible. Relative to control substrates, cellular attachment and proliferation were better on all the scaffold surfaces that were tested. The S2 and S3 samples, those permeated by 1.5 and 2.5 wt% of CG, respectively, exhibited an enhancement in cell spreading capacity compared to the S1 test materials which were comprised of 1 wt% of CG. Excellent osteoblast viability and adhesion were observed for each of the tested materials. Additionally, the bone substitutes developed for this study presented a distinct osteoconductive environment. Data supporting this claim were derived from alkaline phosphatase (ALP) and calcium deposition analyses, which indicated that, compared to the control species, ALP expression and calcium deposition were both improved on test κ-CG/nHA surfaces. In summary, the injectable bone substitute developed here demonstrated great potential for numerous bone regeneration applications, and thus, should be studied further. STATEMENT OF SIGNIFICANCE: The novelty of this work lies in the determination of the in vitro cytocompatibility behavior of carrageenan and hydroxyapatite composite materials used as injectable bone substitutes. This injectable biomaterial can fill in geometric complex defects, and it displays bioactivity as well as high bone regeneration capacity. In this study, we evaluated the behaviors of osteoblast cells in contact with the scaffolds, including cellular adhesion and proliferation, cellular metabolism, and mineralization on the fabricated injectable bone substitutes. The results show than the carrageenan and hydroxyapatite substitutes provided a biomaterial with a great capacity for promoting cellular growth, adhesion, and proliferation, as well as contributing an osteoinductive environment for osteoblast differentiation and osteogenesis.


Assuntos
Substitutos Ósseos , Carragenina , Durapatita , Teste de Materiais , Nanotubos/química , Osteoblastos/metabolismo , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Carragenina/química , Carragenina/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Durapatita/química , Durapatita/farmacologia , Humanos , Osteoblastos/citologia
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