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1.
Inflammopharmacology ; 31(1): 439-449, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36566264

RESUMO

This study identifies the anti-inflammatory, antioxidant, and immunomodulatory potential of a fatty acid methyl ester segregated from the brown algae Turbinaria ornata and identified by nuclear magnetic resonance and mass spectrometry as methyl 6,12-dimethyltridecanoate (ET). Antioxidant and anti-inflammatory effects of ET were studied on lipopolysaccharide (LPS)-induced inflammatory reaction in RAW 264.7 macrophages. Moreover, in silico docking studies of isolated ET with inflammatory markers TNFα, NFκB, and COX-2 showed potent binding scores suggesting anti-inflammatory potential. ET significantly reduced LPO and increased LPS-induced SOD, catalase, and GSH levels. Molecular docking results were further confirmed by checking mRNA levels of selected cytokines (IL6 and IL10), followed by protein expression of iNOS and NFκB in LPS-induced macrophages. ET significantly upregulated the expression of IL10 and downregulated the expression of IL6, iNOS, and NFκB, confirming the inhibition of LPS-induced inflammation via the iNOS/NFκB pathway.


Assuntos
Lipopolissacarídeos , Phaeophyceae , Humanos , Lipopolissacarídeos/farmacologia , Interleucina-6/metabolismo , Antioxidantes/farmacologia , Interleucina-10/metabolismo , Simulação de Acoplamento Molecular , Macrófagos , NF-kappa B/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Phaeophyceae/química , Phaeophyceae/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo
3.
Phytomedicine ; 89: 153615, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34153878

RESUMO

BACKGROUND: Inflammation and oxidative stress are common pathologies in a wide range of chronic diseases. Polysaccharides are known to exhibit antioxidant and anti-inflammatory potential and are suggested to possess immunomodulatory potential. PURPOSE: Herein, the immunomodulatory activity of a sulfated polysaccharide (PS) separated from a brown marine algae Turbinaria ornata is studied in LPS instigated systemic inflammation in experimental rats. STUDY DESIGN AND METHODS: Male SD rats are pretreated with different doses of PS (2.5, 5, 10 mg/kg bw) for a week followed by inducing systemic inflammation using LPS (10 mg/kg i.p.). Blood withdrawn after 8 h of LPS injection is subjected to hematological analysis (WBC, HCT, and PLT). After 24 h of LPS induction, cardiac tissue was isolated and subjected to biochemical, molecular, and histopathological analysis. Effect of PS pre-treatment (2.5, 5, 10 mg/kg bw) was checked by assessing serum parameters (AST, CK-MB, and γGT), antioxidant markers (LPO, GSH, SOD, Grx) and inflammatory markers (IL1ß, IL6, IL10, NFκB), followed by analyzing the iNOS, PI3k and Akt to identify the probable mode of action. RESULTS: Elevated levels of AST, CK-MB, and γGT in serum were significantly reduced on PS pretreatment. LPS significantly raised the LPO and Grx levels in heart tissue whereas, PS pre-treatment significantly reduced LPO and Grx levels. GSH and SOD levels were reduced upon LPS induction and were brought to near normal by HD of PS. PS also reduced the mRNA levels of IL6, Trx, and increased IL10 levels in the heart tissue substantiating its anti-inflammatory and antioxidant potency. Further, IL1ß, NFκB, iNOS, and pPI3k/pAkt expressions were significantly modulated by PS in the cardiac tissue substantiating the immunomodulatory effect. A trend of improvement in the inflammatory pathology was also observed in the heart tissue compared to LPS control, as confirmed by histopathology analysis. CONCLUSION: Altogether, this study concludes the immunomodulatory potential of PS from the marine macroalgae Turbinaria ornata significantly and prevents LPS induced systemic inflammation in the cardiac tissue presumably influenced by the glucopyranose and fucopyranose subunits in the polysaccharide.


Assuntos
Imunomodulação , Inflamação/tratamento farmacológico , Phaeophyceae , Polissacarídeos , Animais , Lipopolissacarídeos , Masculino , Estresse Oxidativo , Phaeophyceae/química , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfatos
4.
Mol Biol Rep ; 47(6): 4465-4475, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32451927

RESUMO

Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28 days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFß, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Xantonas/farmacologia , Animais , Antioxidantes/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Quimioterapia Combinada/métodos , Gliclazida/farmacologia , Hipoglicemiantes/farmacologia , Rim/patologia , Testes de Função Renal/métodos , Masculino , Metformina/farmacologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Xantonas/metabolismo
5.
Phytomedicine ; 59: 152901, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981189

RESUMO

BACKGROUND: Diabetes mellitus poses serious threat to the global population due to the alarming diabetic complications it leads to. The current therapeutic options available can be improved for better efficiency and maximum benefits. Combination therapy has been commonly used to improve the efficacy and to minimize the side effects of drugs in current clinical use. PURPOSE: The present study aims to assess the interaction between a natural molecule mangiferin with the commercially available oral hypoglycemic drugs metformin and gliclazide in diabetic rats. METHODS: In this study, the in vitro cytotoxicity and glucose uptake studies were performed in HepG2 cells. Based on experimental data, the combination index of the hypoglycemic drugs like metformin and gliclazide in combination with different doses of mangiferin was determined using COMPUSYN software. Further, in vivo studies were performed in HFD + STZ induced diabetic male Sprague Dawley rats. Serum parameters, enzyme markers, hepatic oxidative stress markers, gene and protein expression studies and histopathological analyses were performed in rat liver to identify the mode of action of the combination drug administration. RESULTS: The in vitro studies on HepG2 cells suggest a positive interaction of mangiferin with both metformin and gliclazide at specific concentrations as evidenced by glucose uptake. The hepatic enzymes, oxidative stress markers, carbohydrate metabolizing enzymes, gene (AMPK, Akt, ACC ß and Glut-2) and protein (PPARα, PPARγ) expression confirmed the results of the in vitro studies. Both the combinations of mangiferin with metformin and mangiferin with gliclazide exhibited potent antidiabetic effect. The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway). CONCLUSION: The overall results suggest that combination of mangiferin with both metformin and gliclazide alleviates diabetic conditions potentially at specific doses and modulates the adverse effect of high dose of commonly used OHD's. This combination therapy can be translated for its clinical use as a diabetes management strategy.


Assuntos
Gliclazida/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Xantonas/farmacologia , Administração Oral , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Quimioterapia Combinada , Enzimas/genética , Enzimas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gliclazida/administração & dosagem , Células Hep G2 , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metformina/administração & dosagem , Ratos Sprague-Dawley
6.
Exp Toxicol Pathol ; 69(8): 672-680, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28684087

RESUMO

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund's Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Phaeophyceae/química , Polissacarídeos/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/metabolismo , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/análise , Adjuvante de Freund/imunologia , Interleucina-6/sangue , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
7.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 10): o2720, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22065500

RESUMO

In the title compound, C(15)H(10)N(4)O(10), the dihedral angle between the aromatic rings is 89.05 (16)°. One O atom of one of the nitro groups is disordered over two sites in a 0.70:0.30 ratio. In the crystal, the mol-ecules are linked by weak C-H⋯O inter-actions.

8.
Water Sci Technol ; 62(10): 2435-41, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21076231

RESUMO

Environmental contamination by toxic heavy metals is a significant universal problem. The main objective of the study is to use a biodegradable materials like Cyperus pangorei and Chitosan as a composite biosorbent for the removal of Cr(VI) from water. The newly prepared biosorbent is characterized and the capacity of Cr(VI) removal of the biosorbent is carried out systematically by batch mode operations. The adsorption capacity of the biosorbent is examined by changing the parameters like biosorbent dose, varying the initial contact time, varying initial concentration of metal ion and pH of the metal ion solution to know the actual mechanism taking place during the initial sorption process. The experimental data obtained were fitted with the Freundlich, Langmuir and Redlich-Peterson isotherm models and the pseudo first order and the pseudo second order kinetic models. Equilibrium data were fitted very well to the Langmuir Isotherm model and pseudo second order kinetic model. Desorption of the metal ion is also carried out using different concentration of NaOH.


Assuntos
Quitosana/química , Cromo/química , Cyperus/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Metais Pesados/química
9.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 11): o2698, 2010 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-21588914

RESUMO

In the title mol-ecular salt (systematic name: morpholinium 3-hy-droxy-2,4,6-trinitro-phenolate), C(4)H(10)NO(+)·C(6)H(2)N(3)O(8) (-), two of the nitro groups of the anion are close to parallel with the plane of the benzene ring [dihedral angles = 3.46 (9) and 11.60 (10)°] and one is almost perpendicular [dihedral angle = 82.23 (8)°]. An intra-molecular O-H⋯O hydrogen bond occurs in the anion. The morpholinium cation has a slightly distorted chair conformation. In the crystal, the components are linked by simple N-H⋯O and trifurcated N-H⋯(O,O,O) hydrogen bonds.

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