Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 121
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nutr Metab Cardiovasc Dis ; 29(11): 1245-1253, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31439394

RESUMO

BACKGROUND AND AIMS: The novel nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) is effective in the management of elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The aim of the present study was to investigate the effects of the three components on proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of LDL receptor (LDLR) expression, in hepatocyte cell lines and to compare their effects on LDL cellular uptake. METHODS AND RESULTS: HepG2 and Huh7 cells were incubated with B. aristata cortex extract (BCE), red yeast rice (RYR) and M. alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (Western blot analysis and ELISA), PCSK9 mRNA (qPCR) and its promoter activity (luciferase reporter assay). BCE (40 µg/mL) reduced instead PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent reduction of PCSK9 at the mRNA and protein levels, with a maximal reduction at 1 mg/mL, without significant changes of PCSK9 promoter activity. MLE also downregulated the expression of 3-hydroxy-3-methyl-3-glutaryl coenzyme A reductase and fatty acid synthase mRNA levels. The combination of RYR, BCE and MLE reduced the PCSK9 mRNA and protein levels, as well as the promoter activity. Finally, the single components and their combination induced LDL receptor and LDL uptake by the hepatocytes. CONCLUSION: The positive effect of MLE on PCSK9 supports the rationale of using the nutraceutical combination of RYR, BCE and MLE to control hyperlipidemic conditions.


Assuntos
Anticolesterolemiantes/farmacologia , Berberis/química , Produtos Biológicos/farmacologia , LDL-Colesterol/metabolismo , Hepatócitos/efeitos dos fármacos , Lovastatina/farmacologia , Morus/química , Extratos Vegetais/farmacologia , Pró-Proteína Convertase 9/metabolismo , Anticolesterolemiantes/isolamento & purificação , Relação Dose-Resposta a Droga , Regulação para Baixo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Enzimológica da Expressão Gênica , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Pró-Proteína Convertase 9/genética
2.
Anal Bioanal Chem ; 411(22): 5885-5896, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280476

RESUMO

Olive (Olea europaea) processing results in large amounts of by-products that contain valuable molecules such as phenolic compounds and phytosterols. These molecules have demonstrated to reduce blood cholesterol levels. This work proposes the development of a method to obtain simultaneously phenolic compounds and phytosterols from the olive stone using CO2-expanded liquid extraction. Hansen solubility parameters were employed for the theoretical prediction of the most suitable bio-based solvent to extract target compounds. The Box-Behnken experimental design was employed to select the optimal conditions of pressure (8-25 MPa), the molar fraction of CO2 in ethyl acetate (0.15-0.55), and the temperature (40-80 °C). Extracts showing the highest and the lowest reductions of micellar cholesterol solubility capacity were analyzed by gas chromatography coupled to mass spectrometry to find out the compounds responsible for this activity. Different phenolic compounds, free fatty acids, and phytosterols were identified in the extracts. ß-Sitosterol and, especially, tyrosol and hydroxytyrosol were the compounds that primarily contributed to the reduction of micellar cholesterol solubility capacity.


Assuntos
Acetatos/química , Anticolesterolemiantes/isolamento & purificação , Dióxido de Carbono/química , Olea/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Extração Líquido-Líquido/métodos
3.
Pak J Pharm Sci ; 32(1): 69-74, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772792

RESUMO

Mulberry (M. alba L.) has prominent use in traditional Chinese medicine since ancient times but its therapeutic properties have not been sufficiently explored in India. Present study was designed to isolate and identify the polyphenolic constituents present in mulberry leaf (M. latifolia) using HPLC and to evaluate its antihyperglycemic and antihyperlipedemic properties in streptozotocin (STZ) induced diabetic wistar rat models. HPLC analysis identified chlorogenic acid (103mg/100gm), caffeic acid (4.3mg/100gm), coumaric acid (11.61mg/kg), rutin (53mg/100gm) and quercetin (46.19mg/100gm) as the major constituents of crude polyphenolic extracts in M. latifolia. STZ induced diabetic rats administered with mulberry leaf extract at doses 250 and 500mg/kg after 4 weeks of treatment significantly improved their glycemic control (p<0.001). Body weight increased significantly (p<0.001) after administration of BC259 extract at a dose of 500mg/kg. Results also showed that there was a significant decrease in serum urea (p<0.001) and creatinine level (p<0.01). Significant decline was observed in the levels of serum triglycerides (p<0.01), total cholesterol (p<0.001), LDL-cholesterol (p<0.01) and VLDL-cholesterol (p<0.01), while the serum HDL-cholesterol (p<0.01) significantly increased. Results revealed that the leaf extract of M. latifolia (var.BC259) causes significant antidiabetic and antihypercholesterolemic activity. Evidence of identified bioactive polyphenolic compounds present in M. latifolia leaf extract strengthens its antidiabetic property.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Morus , Extratos Vegetais/farmacologia , Folhas de Planta , Polifenóis/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/farmacologia , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/diagnóstico , Hipoglicemiantes/isolamento & purificação , Masculino , Morus/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Polifenóis/isolamento & purificação , Ratos Wistar , Estreptozocina , Triglicerídeos/sangue , Ganho de Peso/efeitos dos fármacos
4.
Int J Biol Macromol ; 124: 796-801, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30500510

RESUMO

Our previous study suggested that extrusion can enhance the soluble dietary fiber (SDF) and improve the physicochemical properties of fiber-rich orange pomace (OP). The aim of this study was to determine the predictive indices for the hypoglycemic, hypocholesterolemic, and fermentation capacities of extruded orange pomace (EOP) with several in vitro assays. The results revealed that EOP could effectively retard glucose diffusion and inhibit α-amylase activity relative to OP. Moreover, EOP had the binding capacities of cholesterol micelles and bile acids. During the in vitro fermentation of EOP, a high content of short chain fatty acid was produced. Scanning electron microscope images showed a more porous and irregular shaped structure of the EOP, which may influence physiological activities, relative to OP. The morphological alterations in the EOP were caused by mechanical shear. Thus, EOP has potential to become a functional food additive for glycemic control and the attenuation of blood cholesterol.


Assuntos
Anticolesterolemiantes/química , Citrus sinensis/química , Fibras na Dieta/análise , Hipoglicemiantes/química , Extração em Fase Sólida/métodos , Anticolesterolemiantes/isolamento & purificação , Ácidos e Sais Biliares/química , Colesterol/química , Fibras na Dieta/metabolismo , Difusão , Ácidos Graxos/química , Fermentação , Frutas/química , Alimento Funcional/análise , Glucose/química , Humanos , Hipoglicemiantes/isolamento & purificação , Micelas , Pressão
5.
J Agric Food Chem ; 67(4): 1104-1114, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30592221

RESUMO

Insoluble residue (INS) is a lignin-rich fraction of brewer's spent grain (BSG) that also contains ß-glucan and arabinoxylan, the major constituents of dietary fiber. We investigated the effects of INS in diet-induced obese mice in terms of lipid metabolism and metabolic diseases. Male mice (C57bl6) were fed a high-fat diet (HFD), a HFD + 20% INS, a HFD + 20% cellulose (CEL), a HFD with a combination of 20% INS-CEL (1:1), or a control diet for 14 weeks. Insulin and glucose tolerance tests were performed after 12 weeks. Fasting plasma lipids, bile acid, and fecal bile acid were measured after 14 weeks of feeding, and tissues were collected for gene expression analysis. Body weight gain was significantly reduced with all fibers, but only INS and INS-CEL decreased fasting plasma low-density lipoprotein cholesterol and total cholesterol compared to HFD. CEL and INS-CEL significantly improved insulin resistance. Fecal bile acids were significantly increased by all fibers, but there was no change in plasma bile acid. Clostridium leptum was increased with all fibers, but universal bacterial diversity was only with INS and INS-CEL. In addition, INS significantly increased the abundance of Bacteriodes, while CEL decreased Atopobium and Lactobacillus. INS feeding significantly upregulated various genes of cholesterol and bile acid metabolism, such as Srebp2, Hmgcr, Ldlr, Cyp7a1, Pparα, Fxr, and Pxr, in the liver. INS, INS-CEL, and CEL significantly attenuated liver steatosis. Our results suggest that INS from BSG induced beneficial systemic changes in mice via gut microbiota, bile acids, and gene expression in the liver.


Assuntos
Anticolesterolemiantes/metabolismo , Grão Comestível/metabolismo , Hipercolesterolemia/metabolismo , Lignina/metabolismo , Resíduos/análise , Animais , Anticolesterolemiantes/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Fibras na Dieta/análise , Fibras na Dieta/metabolismo , Microbioma Gastrointestinal , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/microbiologia , Hipercolesterolemia/fisiopatologia , Lignina/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Ganho de Peso
6.
Nat Prod Res ; 33(5): 651-658, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29139309

RESUMO

Lisosan® Reduction is a plant mixture produced from powder of fermented Triticum aestivum (Lisosan® G), Desmodium adscendens, Malus domestica, Picrorhiza kurroa and Hordeum vulgare. The aim of this study was to characterise the phenolic profile of Lisosan® Reduction and to evaluate the effects of aqueous extract on mice fed a high fat diet (HFD). Syringic acid, trans sinapic acid and neochlorogenic acid were identified by HPLC-DAD to be the dominant polyphenols of Lisosan® Reduction, followed by vitexin, trans p-coumeric acid and trans ferulic acid. Mice treated with aqueous extract of Lisosan® Reduction (60 mg/kg b.w.) showed a significant decrease of serum cholesterol, glucose and triglycerides level and a significant increase of CYP7A1 gene expression, compared to HFD group.


Assuntos
Anticolesterolemiantes/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Polifenóis/isolamento & purificação , Triglicerídeos/sangue
7.
Molecules ; 23(8)2018 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-30060618

RESUMO

Obesity and nonalcoholic fatty liver disease (NAFLD) are highly prevalent and cause numerous metabolic diseases. However, drugs for the prevention and treatment of obesity and NAFLD remain unavailable. In this study, we investigated the effects of mogrosides (luo han guo, LH) in Siraitia grosvenorii saponins on high-fat-diet-induced obesity and NAFLD in mice. We found that compared with the negative control, LH reduced body and liver weight. LH also decreased fat accumulation and increased AMP-activated protein kinase (AMPK) phosphorylation (pAMPK) levels in mouse livers. We also found that high-purity mogroside V upregulated pAMPK expression in HepG2 cells. In addition, high-purity mogroside V inhibited reactive oxygen species production and upregulated sequestosome-1 (SQSTM1, p62) expression in THP-1 cells. These results suggest that LH may affect obesity and NAFLD by enhancing fat metabolism and antioxidative defenses. Mogroside V may be a main component of LH. However, the exact molecular mechanisms and active components responsible for the inhibitory effects of LH on obesity and NAFLD require further investigation.


Assuntos
Fármacos Antiobesidade/farmacologia , Anticolesterolemiantes/farmacologia , Momordica/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Triterpenos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Anticolesterolemiantes/química , Anticolesterolemiantes/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Proteína Sequestossoma-1/agonistas , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Células THP-1 , Triterpenos/química , Triterpenos/isolamento & purificação
8.
Plant Foods Hum Nutr ; 73(2): 101-107, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29679358

RESUMO

In previous studies, it has not been reported that protein isolated from chia interferes favorably with antibacterial activity, and reduces cholesterol synthesis. The objective of this study was to determine whether commonly used commercial microbial proteases can be utilized to generate chia protein-based antibacterial and hypocholesterolemic hydrolysates/peptides, considering the effects of protein extraction method. Alcalase, Flavourzyme and sequential Alcalase-Flavourzyme were used to produce hydrolysates from chia protein (CF), protein-rich fraction (PRF) and chia protein concentrates (CPC1 and CPC2). These hydrolysates were evaluated for their antimicrobial activity against Gram-positive (G+) and Gram-negative (G-) microorganisms. The protein hydrolysates were purified by ultrafiltration through a membrane with 3 kDa nominal molecular weight, for evaluation of hypocholesterolemic activity. An inhibition zone was observed when the hydrolysate was tested against S. aureus, and minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were obtained. Peptides from chia protein with molecular mass lower than 3 kDa reduced up to 80.7% of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) enzymatic reaction velocity. It was also observed that, independent of the method used to obtain chia proteins, the fractions showed relevant bioactivity. Moreover, the intensity of the bioactivity varied with the method for obtaining the protein and with the enzyme used in the hydrolysis process. This is the first report to demonstrate that chia peptides are able to inhibit cholesterol homeostasis.


Assuntos
Antibacterianos/farmacologia , Anticolesterolemiantes/farmacologia , Peptídeos/farmacologia , Hidrolisados de Proteína/farmacologia , Salvia/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/análise , Antibacterianos/isolamento & purificação , Anticolesterolemiantes/análise , Anticolesterolemiantes/isolamento & purificação , Colesterol , Endopeptidases/metabolismo , Hidrólise , Peso Molecular , Peptídeo Hidrolases/metabolismo , Peptídeos/análise , Peptídeos/isolamento & purificação , Hidrolisados de Proteína/análise , Hidrolisados de Proteína/isolamento & purificação , Subtilisinas/metabolismo
9.
J Med Food ; 21(7): 647-653, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29648969

RESUMO

Western-style diets increase the risk for cardiovascular diseases. It is suggested that the risk could be prevented by lowering cholesterol concentrations in blood. In the present study, hypocholesterolemic effects of the probiotics isolated from kimchi (Lactobacillus curvatus KFP419, Leuconostoc paramesenteroides KJP421, and Leuconostoc mesenteroide subsp. mesenteroides KDK411) were investigated in hypercholesterolemia-induced rats. There was no difference in growth performance between the rats fed high cholesterol diet (HCD) and normal diet (ND). However, blood total cholesterol, low-density lipoprotein cholesterol, and hepatic cholesterol were elevated by the HCD compared to ND, and those concentrations were decreased by dietary supplementation of KFP419 and KDK411. It was concomitant with an increase in fecal excretion of neutral sterols (cholesterol, coprostanol, and coprostanone) in the rats fed HCD compared to ND and was even greater with KDK411 supplementation. These findings indicate that probiotics L. curvatus KFP419 and L. mesenteroide subsp. mesenteroides KDK411 isolated from kimchi ameliorate hypercholesterolemia in rats by assimilating and excreting cholesterol in feces.


Assuntos
Anticolesterolemiantes/administração & dosagem , Brassica/microbiologia , Hipercolesterolemia/tratamento farmacológico , Lactobacillus/metabolismo , Leuconostoc mesenteroides/metabolismo , Probióticos/administração & dosagem , Animais , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/metabolismo , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Leuconostoc mesenteroides/genética , Leuconostoc mesenteroides/isolamento & purificação , Masculino , Probióticos/isolamento & purificação , Probióticos/metabolismo , Ratos , Ratos Sprague-Dawley , Verduras/microbiologia
10.
Food Res Int ; 107: 73-83, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29580541

RESUMO

The hypocholesterolemic effect of Lonicera caerulea berry extract rich in polyphenols (LCBP) on high cholesterol-induced hypercholesterolemia and lipoprotein metabolite changes was examined in Caco-2 cells and rats. Cyanidin-3-glucoside, catechin, and chlorogenic acid are the major phenolic components of LCBP. The cholesterol-reducing effect and antioxidant capacity of these components were compared in Caco-2 cells. LCBP (80 µg/mL) and cyanidin-3-glucoside, catechin, and chlorogenic acid (50 µM) were found to be effective (p < 0.05). Rats were fed a high cholesterol diet (HCD) with or without LCBP supplementation (75, 150, and 300 mg/kg body weight intragastrically once daily) for 12 weeks. Compared with the HCD control group, LCBP supplementation at 150 and 300 mg/kg decreased the levels of TC, TG, and LDL-C, but increased that of HDL-C. LCBP treatment promoted greater neutral and acidic sterol excretion (p < 0.05) and improved the antioxidant capacity of the colon tissue, colon contents, and blood. Moreover, trimethylamine N-oxide (TMAO) levels were decreased in serum (p < 0.05). NPC1L1, ACAT2, and MTP mRNA and protein expression were reduced and ABCG5/8 expression was increased (p < 0.05) after LCBP treatment. Our results suggest that LCBP could be used as a functional food for the prevention and treatment of diseases related to excessive cholesterol accumulation.


Assuntos
Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Colesterol/sangue , Frutas , Hipercolesterolemia/prevenção & controle , Lonicera , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Células CACO-2 , Modelos Animais de Doenças , Fezes/química , Frutas/química , Humanos , Hipercolesterolemia/sangue , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipoproteínas/sangue , Lonicera/química , Masculino , Extratos Vegetais/isolamento & purificação , Polifenóis/isolamento & purificação , Ratos Sprague-Dawley , Triglicerídeos/sangue
11.
Food Res Int ; 104: 126-133, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29433777

RESUMO

The effects of CPe-III on hyperlipidemic mice were investigated, along with molecular docking and dynamics analyses between CPe-III and CETP. This study was conducted in order to explore the lipid metabolism potential and mechanism of CPe-III. CPe-III significantly (P<0.05) reduced serum total cholesterol, triglyceride and hepatic triglyceride levels and increased serum superoxide dismutase activity. CPe-III reversed liver changes induced by a high-fat diet and significantly (P<0.05) reduced kidney and epididymal fat indices. The activities of hepatic lipase and lipoprotein lipase, as well as fecal fat excretion, were significantly (P<0.05) enhanced. Furthermore, CPe-III was found to bind in the cavity of CETP, forming four stable hydrogen bonds. Hydrophobic interactions were the main driving force during binding. This study demonstrates that CPe-III improves dyslipidemia in mice. The binding of CPe-III to CETP demonstrates that CPe-III blocks cholesterol transport. These results indicate that CPe-III may be useful as an adjuvant element for hyperlipidemia and atherosclerosis therapies.


Assuntos
Anticolesterolemiantes/farmacologia , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Cicer/química , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Oligopeptídeos/farmacologia , Sementes/química , Adiposidade/efeitos dos fármacos , Animais , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/metabolismo , Sítios de Ligação , Biomarcadores/sangue , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação para Baixo , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hiperlipidemias/sangue , Hiperlipidemias/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/metabolismo , Ligação Proteica
12.
Bioengineered ; 9(1): 12-16, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28632991

RESUMO

Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biologic activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a ß-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes. Triggering the secondary metabolic pathways can be achieved through the variation of cultivation conditions and growth media composition. The alternative strategy is to use genetic engineering to activate the respective genomic segments, e.g. by the manipulation of regulators or chromatin-modifying enzymes. Recently, whole-genome sequencing of several fungi isolated from the Chernobyl accident area was reported by Singh et al. (Genome Announc 2017; 5:e01602-16). These strains were selected for exposure to microgravity at the International Space Station. Biochemical characterization of fungi cultivated under extreme conditions is likely to provide valuable insights into the adaptation mechanism associated with metabolism and, possibly, a catalog of novel molecules of potential pharmaceutical importance.


Assuntos
Produtos Biológicos/isolamento & purificação , Fungos/metabolismo , Regulação Fúngica da Expressão Gênica , Genoma Fúngico , Metabolismo Secundário/genética , Antibacterianos/biossíntese , Antibacterianos/isolamento & purificação , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/metabolismo , Produtos Biológicos/metabolismo , Acidente Nuclear de Chernobyl , Fungos/genética , Fungos/efeitos da radiação , Engenharia Genética , Lovastatina/biossíntese , Lovastatina/isolamento & purificação , Penicilinas/biossíntese , Penicilinas/isolamento & purificação , Metabolismo Secundário/efeitos da radiação , Voo Espacial , Ausência de Peso
13.
Int J Med Mushrooms ; 19(10): 905-913, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29256844

RESUMO

In vivo and in vitro treatments were carried out to investigate the effects of a 95% ethanol extract of Chroogomphus rutilus (CRE) on antioxidant, hypoglycemic, hypolipidemic, and antitumor properties. CRE showed potent radical scavenging activity against DPPH in vitro. It could increase antioxidant enzymatic activities (superoxide dismutase and glutathione peroxidase) and could reduce malondialdehyde content in vivo in mice in which aging was induced by D-galactose. CRE had hypoglycemic activity and could significantly inhibit α-glucosidase activity in vitro and decrease blood glucose concentration in vivo. CRE could decrease the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase the high-density lipoprotein cholesterol level in diabetic mice. The MTT assay showed that CRE also had a certain inhibitory effect on the tumor cells. These results suggest that CRE may be beneficial for human health and could be useful for applications in medicine, the food industry, and agriculture.


Assuntos
Anticolesterolemiantes/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Basidiomycota/química , Hipoglicemiantes/farmacologia , Animais , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/isolamento & purificação , Antineoplásicos/administração & dosagem , Antineoplásicos/isolamento & purificação , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Etanol , Formazans/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Masculino , Camundongos , Solventes , Sais de Tetrazólio/análise
14.
Prep Biochem Biotechnol ; 47(9): 901-908, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-28816626

RESUMO

The elution characteristics of lovastatin were studied by varying the composition of mobile phase in both isocratic and gradient elution modes to comprehend the role of organic modifier and acidifier on the overall analysis time and retention time of individual forms of lovastatin. Acetonitrile has influenced on the overall analysis time, whereas the acidifier determines the retention time of hydroxy acid form of lovastatin and the retention time gap between the individual forms. A combination of acetonitrile and 0.1% trifluoroacetic acid (TFA) (60:40, v/v) in isocratic elution mode eluted both hydroxy acid and lactone forms of lovastatin at 4.5 and 5.4 min, respectively. This appears to be a better approach for the separation of pharmaceutical and clinical lovastatin samples. At isocratic elution mode, a mixture of acetonitrile and either 0.05% TFA or 0.1% H3PO4 of 60:40 (v/v) has eluted both hydroxy acid and lactone forms of lovastatin at 10 ± 0.5 and 17 ± 0.5 min, respectively. This is suitable for the fermentation-derived samples or for the complex mixtures of structural analogs. The fermentation broth (pH not adjusted) extracted with ethyl acetate at a ratio of 1:1 (v/v) at 60°C for 30 min was the optimal extraction condition for lovastatin.


Assuntos
Anticolesterolemiantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Lovastatina/isolamento & purificação , Monascus/metabolismo , Anticolesterolemiantes/química , Anticolesterolemiantes/metabolismo , Fermentação , Microbiologia Industrial , Lovastatina/química , Lovastatina/metabolismo , Monascus/química
15.
Mol Nutr Food Res ; 61(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28730708

RESUMO

SCOPE: The aim of our work was to produce a hydroalcoholic extract of lentils and to examine (a) the hypocholesterolemic action in an animal model, by studying the plasma cholesterol level and the concentration of bile acids in the feces; (b) the potential prebiotic effect, by conducting an in vitro culture fermentation experiment and assessing the level of SCFAs in the feces of rats. METHODS AND RESULTS: Lentil extract (LE) was obtained by extracting lentils with a solution of H2 0/EtOH (70/30 v/v) for 3 h, and the content of main nutrients was determined. After 71 days of diet-induced hypercholesterolemia in rats, LE reduced the cholesterol level of rats of 16.8% (p < 0.05) and increased the level of bile acids in the feces of rats (p < 0.01). LE revealed the same prebiotic activity of inulin and good bifidogenic activity, inasmuch as it enhanced the growth of Bifidobacterium spp. by 3 log (p < 0.05). The concentration of SCFAs in the feces of rats fed with LE increased during the time of the study. CONCLUSION: This new hydroalcoholic extract obtained from lentils was shown to possess hypocholesterolemic and prebiotic properties, and could have interesting applications in the field of nutraceuticals.


Assuntos
Anticolesterolemiantes/uso terapêutico , Microbioma Gastrointestinal , Hipercolesterolemia/dietoterapia , Lens (Planta)/química , Extratos Vegetais/uso terapêutico , Prebióticos , Sementes/química , Animais , Anticolesterolemiantes/química , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/metabolismo , Bifidobacterium/crescimento & desenvolvimento , Bifidobacterium/isolamento & purificação , Bifidobacterium/metabolismo , Ácidos e Sais Biliares/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Contagem de Colônia Microbiana , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fezes/microbiologia , Fermentação , Liofilização , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/microbiologia , Masculino , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Prebióticos/efeitos adversos , Prebióticos/análise , Ratos Sprague-Dawley , Saponinas/análise , Saponinas/isolamento & purificação , Saponinas/metabolismo , Saponinas/uso terapêutico , Triglicerídeos/sangue
16.
Pharm Biol ; 55(1): 974-979, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28164731

RESUMO

CONTEXT: Prunus domestica Linn (Rosaceae) has been considered a functional food, owing to its various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic and anticancer. OBJECTIVE: This placebo-controlled, randomized study was framed to check the beneficial activity of prune essence concentrates (PEC) in corroboration with intestinal function and lipid profile in mildly hypercholesterolemic subjects. MATERIALS AND METHODS: Sixty healthy mild hypercholesterolemic subjects were randomly chosen and segregated into three groups as placebo (consume 50 mL of simulated prune drink), PEC I (consume 50 mL of PEC/day) and PEC II (consume 100 mL of PEC/day) for 4 weeks with 2 weeks of follow-up without PEC consumption. RESULTS: Intake of PEC (I and II) for 4 weeks substantially ameliorated (p < 0.05) the colony number of Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p < 0.05) the colony number of Clostridium perfringens (5.97 and 8.35%) and Escherichia coli (6.25 and 9.38%). Meanwhile, the total cholesterol (TC; 5.90 and 6.99%) levels and LDL-c (6.68 and 6.53%) were significantly reduced (p < 0.05), but no change in other lipid parameters. Whereas, the antioxidant capacity was also concomitantly elevated (p < 0.05) upon administration with PEC. DISCUSSION AND CONCLUSION: Overall, the results suggest that the use of PEC may positively regulate the intestinal microflora and thereby effectively lower the TC levels and thus act as a hypocholesterolemic agent.


Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Sucos de Frutas e Vegetais , Fármacos Gastrointestinais/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Intestinos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Prunus domestica/química , Adolescente , Adulto , Anticolesterolemiantes/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Biomarcadores/sangue , Contagem de Colônia Microbiana , Regulação para Baixo , Fezes/microbiologia , Feminino , Fármacos Gastrointestinais/isolamento & purificação , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Intestinos/microbiologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Índice de Gravidade de Doença , Taiwan , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
J Ethnopharmacol ; 198: 399-406, 2017 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28115286

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia condensata Baker (Asteraceae) is traditionally used in South American Countries as an anti-inflammatory, analgesic and hepatoprotective. AIM OF THE STUDY: This study aimed to investigate the in vivo hepatoprotective and antioxidant, and the in vitro anti-inflammatory activities of the ethyl acetate partition (EAP) from the ethanolic extract of this medicinal plant leaves. MATERIALS AND METHODS: For the in vivo hepatoprotective activity, rats were pretreated orally for seven days with vehicle, silymarin 100mg/kg or EAP 50, 100 and 200mg/kg. Then, acetaminophen 3g/kg was also orally administrated. Animals were euthanatized 24h after the damage inducement. The levels of the serum enzymes ALT, AST and ALP were determined, as well as the triglycerides, total cholesterol and fractions. The antioxidant activity was evaluated by TBARS assay and by the measurement of glutathione reductase, superoxide dismutase and catalase activities in the rats liver tissue. The in vitro anti-inflammatory assay using Raw 264.7 cell line induced by lipopolysaccharide was conducted to verify EAP ability to inhibit pro-inflammatory cytokines. RESULTS: EAP was able to inhibit all the acute biochemical alterations caused by acetaminophen overdose. EAP inhibited malondialdehyde formation, maintained the catalase and increased the glutathione reductase activities. Also, EAP decreased NO, IL-6 and TNF-α levels at concentrations from 10 to 20µg/mL. 1,5-dicaffeoylquinic acid was isolated and identified as the major compound in EAP. Apigenin, luteolin, chlorogenic acid were also identified. EAP anti-inflammatory action may be due to its antioxidant activity or its capacity to inhibit the pro-inflammatory cytokines. CONCLUSION: These results strongly suggested that V. condensata may be useful as a possible therapy against liver damage.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais/farmacologia , Vernonia/química , Acetaminofen/administração & dosagem , Acetaminofen/toxicidade , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Overdose de Drogas , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos Wistar , Silimarina/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-29473534

RESUMO

BACKGROUND: Ligaria cuneifolia (Lc) (R. et P.) Tiegh. (Loranthaceae) (Argentine mistletoe) is usually used in local folk medicine. OBJECTIVE: We studied the effect of treatment with the Lc proanthocyanidin-enriched fraction (PLc) in rats fed with Cho-enriched diet on plasma lipids levels, the hemorheological parameters, and biliary secretion. METHOD: Adult male Wistar rats were fed ad libitum with a Cho-enriched diet (Cho (97% purity) 8 g/kg of diet and corn oil 280 g/kg of diet) during 28 days. Then, were separated in six experimental groups (n=5 each one), which were injected ip every 24 h with: 1) saline solution (control group, C) and 2) PLc, 3 mg/100 g body weight (treated group, C+PLc), during 3, 7 and 10 days. Group C presented an increase in plasma levels of Cho and Triglycerides (TG), and also, accumulation of hepatic lipid droplets. Also, cell shape and their corresponding morphological index (MI) were altered too. RESULTS: The treatment with PLc at 3, 7 and 10 days produces a diminution in the plasma Cho, LDL-Cho and serum TG levels, accompanied by a diminution of the lipid accumulation in the liver. The rates of bile acid output in bile can explain the diminution of plasma Cho, evidencing that some of the enzymes involved in the cholesterol conversion into bile acids could be up regulated by the treatment with PLc, leading to the observed increase bile flow. PLc treatment leads to a diminution of plasma levels of Cho and TG. CONCLUSION: Essentially, the treatment with PLc, despite the duration produces a modification in hemorheological parameters approaching the values of the experimental group with standard diet. Plasma levels of Cho, LDL-Cho and TG represent selected markers to evaluate the effect of enriched extract from Ligaria cuneifolia. Further work is necessary to better evaluate the mechanisms by which PLc induces modifications in the lipids metabolism.


Assuntos
Anticolesterolemiantes/farmacologia , Colesterol na Dieta/sangue , Hipercolesterolemia/prevenção & controle , Loranthaceae , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Biomarcadores/sangue , Modelos Animais de Doenças , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Loranthaceae/química , Masculino , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proantocianidinas/isolamento & purificação , Ratos Wistar , Fatores de Tempo , Triglicerídeos/sangue
19.
Arch Physiol Biochem ; 123(1): 23-30, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27424611

RESUMO

AIM: We evaluated the potential preventive and therapeutic effects of Crataegus aronia (C. aronia) in NAFLD induced by high-fat diet (HFD) in rat models. METHODS: Protective effect of Crataegus aronia or simvastatin was investigated in Wistar rats fed either low-fat diet (LFD) or HFD. RESULTS: Liver histopathological examinations confirmed the development of NAFLD in rats fed HFD. In both protective and therapeutic treatments, C. aronia significantly reduced liver index (3.85 ± 0.21% in HFD plus aronia group versus 6.22 ± 0.58% in HFD model group), increased the HDL-cholesterol and reduced the LDL-cholesterol in blood. The hawthorn plant also significantly ameliorated oxidative stress biomarker (p < 0.002) and liver enzymes (p < 0.0001) that indicate liver damage. CONCLUSION: C. aronia exhibits therapeutic and protective effects on NAFLD in an animal model possibly by its lipid lowering and antioxidant effects; thus, may offer therapeutic potential in humans.


Assuntos
Anticolesterolemiantes/uso terapêutico , Antioxidantes/uso terapêutico , Lipotrópicos/uso terapêutico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/isolamento & purificação , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Biomarcadores/metabolismo , HDL-Colesterol/agonistas , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Crataegus/efeitos adversos , Crataegus/química , Crataegus/crescimento & desenvolvimento , Dieta com Restrição de Gorduras , Dieta Hiperlipídica/efeitos adversos , Jordânia , Lipotrópicos/efeitos adversos , Lipotrópicos/isolamento & purificação , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Masculino , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/crescimento & desenvolvimento , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Distribuição Aleatória , Ratos Wistar , Sinvastatina/efeitos adversos , Sinvastatina/uso terapêutico
20.
Fitoterapia ; 115: 111-121, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27713083

RESUMO

The aim of this study was to investigate the antihypercholesterolemic activity and potential molecular mechanism of columbamine (COL) that was prepared by extraction from Rhizoma Coptidis in hamsters and HepG2 cells. The results displayed that the COL from Rhizoma Coptidis was a safe natural compound with a LD50 0f 1524.6mg/kg and no detectable toxic symptoms during the observation of chronic toxicity. COL dose-dependently reversed the abnormal lipid levels induced by HFHC diet. Specifically, COL(M) and COL(H) significantly reduced the blood lipid levels(TC, TG and LDL-c) and enhanced the fecal contents of TBA by 21.8% and 25.1% respectively in hamsters. COL up-regulated the genes of CYP8B1, CYP7A1 and LDLR in mRNA and protein level, and down-regulated those of HMGCR to a different degree. Especially, CYP7A1 were significantly up-regulated by COL in hamsters (p<0.01). Further analysis indicated that COL obviously activated the mRNA and protein expression of the transcription factors FTF, HNF-4α, and inhibited those of SHP. Promoter luciferase assay showed that COL induced the expression of FTF and HNF-4α, further transactivating CYP7A1, which accelerated the conversion of liver cholesterol to bile acids. It concluded that the COL showed high lipid-lowering activities through indirectly transactivating CYP7A1 by upregulating FTF and HNF-4α, and directly activating CYP7A1 catalytic activity by strongly interacting with receptor and ligand, therefore promoting cholesterol catabolism and accelerating the excretion of bile acids.


Assuntos
Anticolesterolemiantes/química , Alcaloides de Berberina/química , Colesterol 7-alfa-Hidroxilase/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Fatores de Transcrição/metabolismo , Animais , Anticolesterolemiantes/isolamento & purificação , Alcaloides de Berberina/isolamento & purificação , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Coptis/química , Cricetinae , Medicamentos de Ervas Chinesas/química , Feminino , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Rizoma/química , Testes de Toxicidade , Ativação Transcricional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA