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1.
Food Chem ; 351: 129340, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33662904

RESUMO

Type 3 resistant starch (RS3) was developed from Canna edulis (Ce) native starch (NS) through dual enzymatic hydrolysis and recrystallization. Thereafter, the processed Ce-RS3 was subjected to systematic characterizations for its structural properties, anti-hyperlipidemic effect, and in vivo gut microbiota modulatory function. The Ce-RS3 content was increased to 49.11% after processing under optimal conditions. Compared with NS, Ce-RS3 maintained its B-type crystallization without introducing new chemical groups. Meanwhile, it displayed coarse surfaces, higher crystallinity, more ordered structures, and a higher proportion of chains with degree of polymerization (DP) 37-100. Ce-RS3 intervention significantly alleviated dyslipidemia in hyperlipidemic mice, which was associated with increased gut microbial diversity and unique microbial enrichment, potentially mediated by its fine structure. These observations are valuable for developing RS3 from C. edulis for prebiotics applications and support the potential strategy that utilizes well-designed RS to modulate specific bacterial populations to improve health.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Zingiberales/química , Animais , Hidrólise , Camundongos
2.
Food Chem ; 333: 127478, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663752

RESUMO

Moringa oleifera Lam. (M. oleifera) leaves have long been consumed as both nutritive vegetable and popular folk medicine for hyperglycemia and hyperlipidemia in Kenya communities. In the current study, in vitro inhibition by M. oleifera leaf extract (MOLE, 90% (v/v) ethanol) of α-glucosidase and pancreatic lipase was demonstrated, followed by determination of the effects of MOLE on both glucose consumption and lipid levels (TC, TG, HDL-C and LDL-C) in 3T3-L1 cells. Potential ligands in MOLE were fast screened using affinity ultrafiltration LC-MS, and 14 and 10 components displayed certain binding affinity to α-glucosidase and pancreatic lipase, respectively. Docking studies revealed the binding energies and hydrogen bonds between potential ligands and enzymes. This study suggests that M. oleifera leaves may be a promising natural source for the prevention and treatment of hyperglycemia and hyperlipidemia as well as a functional food or other product for health care in the near future.


Assuntos
Moringa oleifera/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células 3T3-L1 , Animais , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Lipase/antagonistas & inibidores , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos
3.
Artigo em Inglês | MEDLINE | ID: mdl-32384714

RESUMO

NoveLin I and NoveLin II are palm-based oils. NoveLin I has an equal distribution of saturated, monounsaturated and polyunsaturated fatty acids, whereas NoveLin II has a moderate level of monounsaturated fatty acids, and a lower content of saturated and polyunsaturated fatty acids. However, their hypocholesterolaemic and anti-atherogenic effects have not been studied. Therefore, this study aimed to assess the hypocholesterolaemic and anti-atherogenic effects of these oils. Forty male New Zealand White rabbits were divided into four groups and fed with diets containing 35% energy fat with added 0.15% (w/w) dietary cholesterol. Group 1, as the control group (CNO) was fed with a diet containing coconut oil, group 2 and 3 were fed with diets containing either NoveLin I or NoveLin II, and group 4, was fed with diet containing olive oil (OLV) for 100 days. Our results demonstrated that both NoveLin groups have significantly lower total cholesterol and low-density lipoprotein-cholesterol (LDL-C) compared to CNO group and are comparable to the OLV group. Low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL/HDL-C) ratio was significantly lower after the NoveLin II diet but attained significance only in comparison to NoveLin I and CNO groups. Aortic fibrous plaque score was significantly lower in both NoveLin groups compared to CNO group. Our findings suggest that despite the high-fat cholesterol diet, NoveLin II oil resulted in atherogenic effects comparable to olive oil.


Assuntos
Aterosclerose/etiologia , Gorduras na Dieta/administração & dosagem , Hipolipemiantes/química , Óleos Vegetais/administração & dosagem , Animais , Colesterol , Óleo de Coco , Hipolipemiantes/administração & dosagem , Masculino , Óleos Vegetais/química , Coelhos
4.
J Agric Food Chem ; 68(14): 4237-4244, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32186189

RESUMO

Previous studies demonstrated that peptides produced by the hydrolysis of olive seed proteins using Alcalase enzyme showed in vitro multifunctional lipid-lowering capability. This work presents a deeper insight into the hypolipidemic effect of olive seed peptides. The capability of olive seed peptides to inhibit endogenous cholesterol biosynthesis through the inhibition of HMG-CoA reductase enzyme was evaluated observing a 38 ± 7% of inhibition. Two in vivo assays using different peptides concentrations (200 and 400 mg/kg/day) were designed to evaluate the hypolipidemic effect of olive seed peptides in male and female mice. A low concentration of hydrolysate reduced total cholesterol in male mice in a 20% after 11 weeks compared to the mice feeding with hypercholesterolemic diet. A higher hydrolysate concentration showed a greater reduction in total cholesterol (25%). The analysis of the olive seed hydrolysate by reverse phase high-performance liquid chromatography mass spectrometry (RP-HPLC-MS) enabled the identification of peptides that could be responsible for this hypolipidemic effect.


Assuntos
Hipolipemiantes/química , Olea/química , Peptídeos/química , Extratos Vegetais/química , Sementes/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/biossíntese , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Dieta , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Hidrólise , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipolipemiantes/farmacologia , Masculino , Camundongos , Peptídeos/farmacologia , Extratos Vegetais/farmacologia , Hidrolisados de Proteína/química , Espectrometria de Massas em Tandem
5.
Int J Biol Macromol ; 147: 428-438, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31899245

RESUMO

Two polysaccharide fractions (SFPs, designated as respectively SFP-1 and SFP-2) were acquired from Sargassum fusiforme by ultrasound-assisted enzymatic extraction, and their physicochemical properties and hypoglycemic and hypolipidemic effects were investigated. Structural analysis indicated that SFPs were obvious different in the zeta potential, molecular weight distribution, characteristic organic group, microstructure and the contents of total sugar, uronic acid, sulfate and moisture. SFPs consisted of fucose, mannose, rhamnose, glucose, galactose and glucuronic acid with different molar ratios. Congo red test explained that SFPs had no triple-helix structure. SFP-1 exhibited lower viscosity due to its lower molecular weight. Regarding to hypoglycemic and hypolipidemic effects, oral administration of SFPs prominently restrained loss of body weight and increase of water intake, and also significantly controlled the increase of levels of fasting blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), uric acid (UA), urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of diabetic rats, and SFP-2 showed better effects in controlling fasting blood glucose, ALT, UA and BUN levels. Intervention of SFP-2 reduced the levels of insulin, FFA and TBA of diabetic rats. Histomorphological observation further demonstrated that SFPs could attenuate liver and kidney damage caused by hyperglycemia and hyperlipidemia. Data indicated that SFPs, especially SFP-2, significantly improved hyperglycemia, hyperlipidemia and liver and kidney function of diabetic rats.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes , Hipolipemiantes , Polissacarídeos , Sargassum/química , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Masculino , Polissacarídeos/química , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley
6.
Eur J Pharmacol ; 868: 172871, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31846627

RESUMO

Niacin has been widely used as an antihyperlipidemic drug, but the flushing effect restricted its clinical application. Here, we developed novel niacin-lipoic acid dimers which lead to better lipid modulation, higher synergistic effects and less side effects. We utilized molecular docking simulation to design a novel series of niacin-lipoic acid dimers. The compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide (N2L) was selected for the in vitro and in vivo evaluation, including the agonist activity in CHO-hGPR109A cells, cell protective effects in HT22 and HUVECs cells, flushing effect in guinea pigs and rats, lipid modulation in C57BL/6 mice and high fat diet-rats and atherosclerotic lesions regulation in apolipoprotein E null mice. N2L worked as potent and selective agonists for the high affinity niacin receptor GPR109A. N2L retained antioxidation and cytoprotection of lipoic acid. In addition, N2L displayed a good therapeutic index regarding lipid modulation and atherosclerotic lesions regulation, and minimized niacin-induced vasodilation (flushing) effect in vivo. N2L showed effective treatment regarding to lipid regulation and atherosclerosis inhibition effects, also with excellent antioxidant effects, safety profiles and non-flushing. All these results suggest N2L promising application prospects in the drug development for the treatment of atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Rubor/prevenção & controle , Hipolipemiantes/farmacologia , Animais , Aterosclerose/sangue , Aterosclerose/diagnóstico , Linhagem Celular , Cricetulus , Dimerização , Modelos Animais de Doenças , Desenho de Fármacos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Rubor/induzido quimicamente , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipolipemiantes/química , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Masculino , Camundongos , Camundongos Knockout para ApoE , Simulação de Acoplamento Molecular , Niacina/química , Niacina/farmacologia , Niacina/uso terapêutico , Ratos , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico
7.
Colloids Surf B Biointerfaces ; 186: 110718, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846890

RESUMO

Atherosclerotic lesions create obvious vascular stenosis due to the presence of plaque, and a large number of inflammatory macrophages are enriched in the thrombus. In this study, we develop a composite hydrogel drug delivery system that is capable of both mechanically-sensitive drug release and of targeting inflammatory macrophages at the thrombus. The hydrogel is a high molecular weight hyaluronic acid (HA) modified with glycidyl methacrylate as a hydrogel precursor; a cross-linkable block copolymer (CBC) is used as the drug coating material and a microscopic cross-linking agent. The difference in drug release rate of the composite hydrogel (HACBC) in simulated blood vessels with 0 % and 75 % occlusion was as high as 49.3 %. Under long-term cycling conditions in stenotic vessels, dynamic shear rheometry revealed that the HACBC still maintained the hydrogel properties. However, the micelles were deformed and recombined to produce smaller sized micelles. An in vitro cell culture demonstrated precise targeting of the HACBC to inflammatory macrophages, and our rabbit experiments with simvastatin-coated HACBC confirmed the effective release of simvastatin in the plaque of the drug carrier. Moreover, we demonstrated the precise targeting of HACBC in vivo in apoE-/- mice by using HACBC coated with cy7. The mechanical stress-sensitive and CD44 receptor-targeted dual-response drug delivery system prepared by micellar composite hydrogel is the first application in the field of atherosclerosis, which provides a new method for diagnosing and treating atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Hidrogéis/química , Hipolipemiantes/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Sinvastatina/farmacologia , Animais , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Hidrogéis/síntese química , Hipolipemiantes/química , Inflamação/diagnóstico , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Micelas , Tamanho da Partícula , Sinvastatina/química , Propriedades de Superfície
8.
Pharm Dev Technol ; 25(2): 168-177, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31642728

RESUMO

Fenofibrate is antihyperlipidemic which has low and variable oral bioavailability due to erratic dissolution characteristics. Niacin showed a potential atheroprotective effects suggesting possible co-administration with fenofibrate with a potential for development of fixed dose combination. The chemical structure of both drugs highlights the opportunity for interaction upon co-processing due to the existence of complementary hydrogen bonding sites. Accordingly, fenofibrate and niacin were co-processed by wet co-grinding and the resulting product was assessed using scanning electron microscopy, FTIR, thermal analysis and X-ray diffraction in addition to dissolution studies. The instrumental analysis indicated the development of submicron fenofibrate crystals stabilized over the surface of niacin crystals. The developed submicron crystals showed fast dissolution of fenofibrate depending on the relative proportions of fenofibrate to niacin. Co-processing of both drugs at dose ratio which contained higher proportion of niacin resulted in further enhancement in the dissolution rate. This further enhancement was attributed to the hydrotropic effect of niacin which was proved by solubility study in addition to size reduction. This supposition was confirmed from the inferior dissolution of fenofibrate from the physical mixture. The study introduces fenofibrate/niacin as potential fixed dose combination for augmented dissolution rate and pharmacological effects.


Assuntos
Portadores de Fármacos/química , Fenofibrato/química , Niacina/química , Administração Oral , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Ligação de Hidrogênio/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Hipolipemiantes/química , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
9.
Mini Rev Med Chem ; 20(2): 96-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31518223

RESUMO

Natural polysaccharide is a kind of natural macromolecular which can be extracted from plants, fungi, algae, animals, and bacteria. The monosaccharide compositions and glucosidic bonds of polysaccharides from different origins vary substantially. Natural polysaccharides have been shown to possess complex, important and multifaceted biological activities including antitumor, anticoagulant, antioxidative, antiviral, immunomodulatory, antihyperlipidemic and antihepatotoxic activities. Their properties are mainly due to their structural characteristics. It is necessary to develop polysaccharide immunomodulators with potential for preventive or therapeutic action. The present paper summarizes the structural features, immunostimulatory activity and the immunomodulatory mechanisms of natural polysaccharides. In particular, it also provides an overview of representative natural polysaccharide immunomodulators.


Assuntos
Antioxidantes/farmacologia , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Hipolipemiantes/farmacologia , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Antivirais/química , Produtos Biológicos/química , Configuração de Carboidratos , Humanos , Hipolipemiantes/química , Fatores Imunológicos/química , Polissacarídeos/química
10.
Sci Rep ; 9(1): 16105, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695118

RESUMO

Atorvastatin, a favored option for hyperlipidemia exhibits the problem of poor gastric solubility and low absolute bioavailability (12%) along with higher pre-systemic clearance (>80%). Therefore, to circumvent these limitations, atorvastatin nanocrystals were prepared using poloxamer-188 as stabilizer via high pressure homogenization technique followed by lyophilization. Various variables like drug to poloxamer-188 ratio, homogenization cycle, homogenization pressure, type and concentration of cryoprotectant were optimized to achieve uniform nanosized crystals with good dispersibility. Solid state characterization by ATR-FTIR and DSC revealed no incompatible physicochemical interaction between drug and excipients in formulation while DSC and PXRD collectively corroborated the reduced crystallinity of drug in nanocrystals. Size analysis and SEM confirmed nanometric size range of nanocrystals (225.43 ± 24.36 nm). Substantial improvement in gastric solubility (~40 folds) and dissolution rate of drug in nanocrystals was observed. Pharmacokinetic study in wistar rats revealed significant improvement in oral bioavailability (~2.66 folds) with atorvastatin nanocrystals compared to pure drug. Furthermore, reduction in serum total lipid cholesterol, LDL and triglyceride content justified the effectiveness of formulation at 50% less dose of atorvastatin along with improved plasma safety profile in comparison of pure drug. In conclusion, atorvastatin nanocrystals are safe and efficacious drug delivery system confirming potent competence in treatment of hyperlipidemic conditions with ease of scalability for commercialization.


Assuntos
Atorvastatina/química , Sistemas de Liberação de Medicamentos/métodos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Animais , Atorvastatina/administração & dosagem , Atorvastatina/efeitos adversos , Atorvastatina/farmacocinética , Disponibilidade Biológica , LDL-Colesterol/metabolismo , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Liberação Controlada de Fármacos , Humanos , Hiperlipidemias/metabolismo , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacocinética , Nanoestruturas/administração & dosagem , Nanoestruturas/efeitos adversos , Nanoestruturas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Triglicerídeos/metabolismo
11.
Int J Mol Sci ; 20(19)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581697

RESUMO

The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.


Assuntos
Antrodia/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Triterpenos/farmacologia , Animais , Biomarcadores , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipoglicemiantes/química , Hipolipemiantes/química , Fígado/metabolismo , Fígado/patologia , Camundongos , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triterpenos/química
12.
Mar Drugs ; 17(10)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569458

RESUMO

Fungal marine microorganisms are a valuable source of bioactive natural products. Fungal secondary metabolites mainly comprise alkaloids, terpenoids, peptides, polyketides, steroids, and lactones. Proteins and peptides from marine fungi show minimal human toxicity and less adverse effects comparable to synthetic drugs. This review summarizes the chemistry and the biological activities of peptides that were isolated and structurally elucidated from marine fungi. Relevant fungal genera including Acremonium, Ascotricha, Aspergillus, Asteromyces, Ceratodictyon, Clonostachys, Emericella, Exserohilum, Microsporum, Metarrhizium, Penicillium, Scytalidium, Simplicillium, Stachylidium, Talaromyces, Trichoderma, as well as Zygosporium were extensively reviewed. About 131 peptides were reported from these 17 genera and their structures were unambiguously determined using 1D and 2D NMR (one and two dimensional nuclear magnetic resonance) techniques in addition to HRMS (high resolution mass spectrometry). Marfey and Mosher reactions were used to confirm the identity of these compounds. About 53% of the isolated peptides exhibited cytotoxic, antimicrobial, and antiviral activity, meanwhile, few of them showed antidiabetic, lipid lowering, and anti-inflammatory activity. However 47% of the isolated peptides showed no activity with respect to the examined biological activity and thus required further in depth biological assessment. In conclusion, when searching for bioactive natural products, it is worth exploring more peptides of fungal origin and assessing their biological activities.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Fungos/química , Peptídeos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Peptídeos/química , Peptídeos/isolamento & purificação
13.
Food Funct ; 10(11): 7378-7386, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31651924

RESUMO

Previous studies have shown that 7S protein is the active ingredient responsible for the plasma cholesterol-lowering activity of soybean. It is hypothesized that isoflavones in soybean could enhance the blood cholesterol-lowering activity of 7S protein. Forty-eight hamsters were divided into six groups and fed a non-cholesterol diet or one of the five high-cholesterol diets containing 12.1% 7S protein with 0-15.62 mg g-1 isoflavones. The results showed that addition of isoflavones in diets dose-dependently enhanced the plasma total cholesterol-lowering activity of 7S protein. Addition of isoflavones in 7S protein-based diets significantly reduced hepatic cholesterol accumulation by 12.6-26.1%, compared with the high cholesterol control diet. Isoflavones could also facilitate excretion of neutral sterols in a dose-dependent manner. Supplementation of isoflavones in diets favourably modulated mRNA expression and the protein mass of HMG-CoA reductase. It was concluded that the enhancing effect of isoflavones on the blood cholesterol-lowering activity of 7S protein was mediated by inhibiting the cholesterol absorption and de novo cholesterol synthesis in hypercholesterolemic hamsters.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/farmacologia , Isoflavonas/farmacologia , Proteínas de Plantas/farmacologia , Ração Animal/análise , Animais , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Colesterol/metabolismo , Cricetinae , Dieta/veterinária , Fezes/química , Regulação da Expressão Gênica/efeitos dos fármacos , Hipolipemiantes/química , Isoflavonas/química , Fígado/química , Fígado/metabolismo , Masculino , Proteínas de Plantas/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Soja/química
14.
Sci Rep ; 9(1): 14266, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582800

RESUMO

Hyperlipidemia, a very common disease throughout the world, usually gives rise to severe liver damages. The current experiment was to investigate the antihyperlipidemic and hepatoprotective properties of alkali- and enzyme-extractable Dictyophora indusiata polysaccharides (Al-DPS and En-DPS) on the hyperlipidemic mice. The results of animal experiment in vivo showed that treatment with Al-DPS or En-DPS could improve the excessive level of lipid profiles in serum and liver, as well as strengthen antioxidant status. In addition, the histopathological observations of liver testified that polysaccharides were capable of attenuating hepatic cell injury. The primary structural features of Al-DPS and En-DPS were demonstrated by HPGPC, HPLC, FT-IR and NMR. Glucose tolerance test manifested that polysaccharides were able to restrain the rise of blood sugar. The results indicated that Al-DPS and En-DPS may be considered as novel compounds to treat hyperlipidemia and also act as hepatoprotective agents.


Assuntos
Basidiomycota , Polissacarídeos Fúngicos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Basidiomycota/química , Polissacarídeos Fúngicos/química , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hipolipemiantes/química , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Substâncias Protetoras/química
15.
Chin J Nat Med ; 17(9): 663-671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31526501

RESUMO

Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids, ellipticine (1) and 9-methoxyellipticine (2), and six known monoterpenoid indole alkaloids (3-8). Lipid-lowering assay in 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC50 = 0.41 and 0.92 µmol·L-1, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 µmol·L-1, being more potent than the positive drug luteolin (EC50 = 2.63 µmol·L-1). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-L1 cells at the early differentiation phase, leading to the retardance of following adipogenesis and lipogenesis. These findings suggest that 1 and 2 may serve as promising leads for further development of anti-obesity drugs.


Assuntos
Adipogenia/efeitos dos fármacos , Carbazóis/farmacologia , Proliferação de Células/efeitos dos fármacos , DNA Super-Helicoidal/química , Hipolipemiantes/farmacologia , Ochrosia/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Carbazóis/química , Carbazóis/metabolismo , Dano ao DNA , Elipticinas/química , Elipticinas/metabolismo , Elipticinas/farmacologia , Hipolipemiantes/química , Hipolipemiantes/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Inibidores da Topoisomerase/química , Inibidores da Topoisomerase/metabolismo , Inibidores da Topoisomerase/farmacologia
16.
Int J Pharm ; 570: 118661, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31491482

RESUMO

There have been many strategies to increase solubility, dissolution rates, and oral bioavailability of fenofibrate such as micronization, nanonization, solid dispersion, and emulsion so far. To our knowledge, only first three technologies have been applied in producing marketed products, and no combination of solid dispersion and pellet has been found even in laboratory-based reports. Therefore, the aim of this study was to develop novel solid dispersion-based pellets via an one-step process directly from fenofibrate powder using layering method. Developed fenofibrate pellets were in vitro characterized on size distribution, dissolution rates, sensory evaluation and stability. In addition, the transformation from crystalline fenofibrate to amorphous fenofibrate, and intermolecular interactions of fenofibrate in solid dispersion were confirmed using physico-chemical methods. The dissolution rate of pellets containing fenofibrate was significantly higher than that of the reference, Lipanthyl® 160 mg tablets at early stage, satisfying the criteria in USP 38. The pellets, then, were packed in hard capsules for bioequivalence studies in experimental beagle dogs using a validated HPLC assay. Final findings of the present study should be beneficial for further development of new fenofibrate formulations containing solid dispersion-based pellets which were bioequivalent to Lipanthyl® 160 mg tablets.


Assuntos
Implantes de Medicamento/química , Fenofibrato/química , Administração Oral , Animais , Disponibilidade Biológica , Cápsulas/química , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cães , Emulsões/química , Hipolipemiantes/química , Masculino , Tamanho da Partícula , Solubilidade/efeitos dos fármacos , Comprimidos/química , Equivalência Terapêutica
17.
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
18.
Int J Biol Macromol ; 140: 782-793, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401268

RESUMO

Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide­chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ±â€¯1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.


Assuntos
Basidiomycota/química , Cromo/química , Polissacarídeos Fúngicos/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/etiologia , Dieta Hiperlipídica , Teste de Tolerância a Glucose , Masculino , Camundongos , Análise Espectral
19.
Eur J Med Chem ; 181: 111557, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374419

RESUMO

Many potential pharmacological targets are present in multiple subcellular compartments and have different pathophysiological roles depending on location. In these cases, selective targeting of a drug to the relevant subcellular domain(s) may help to sharpen its impact by providing topological specificity, thus limiting side effects, and to concentrate the compound where needed, thus increasing its effectiveness. We review here the state of the art in precision subcellular delivery. The major approaches confer "homing" properties to the active principle via permanent or reversible (in pro-drug fashion) modifications, or through the use of special-design nanoparticles or liposomes to ferry a drug(s) cargo to its desired destination. An assortment of peptides, substituents with delocalized positive charges, custom-blended lipid mixtures, pH- or enzyme-sensitive groups provide the main tools of the trade. Mitochondria, lysosomes and the cell membrane may be mentioned as the fronts on which the most significant advances have been made. Most of the examples presented here have to do with targeting natural compounds - in particular polyphenols, known as pleiotropic agents - to one or the other subcellular compartment.


Assuntos
Produtos Biológicos/farmacologia , Hipolipemiantes/farmacologia , Polifenóis/farmacologia , Animais , Produtos Biológicos/química , Membrana Celular/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Humanos , Hipolipemiantes/química , Lipossomos/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Polifenóis/química
20.
BMC Complement Altern Med ; 19(1): 230, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443712

RESUMO

BACKGROUND: Hyperglycemia and dyslipidemia are classic features of patients with diabetes mellitus (DM). Cordyceps taii, a folk medicinal fungus native to southern China, possesses various pharmacological activities. This study aimed to assess the glucose-lowering and hypolipidemic effects of polysaccharides from C. taii (CTP) in streptozotocin (STZ)-induced diabetic mice. METHODS: Kunming mice were intraperitoneally injected with STZ at a dose of 100 mg/kg body weight. After induction of diabetes, diabetic mice were randomly divided into five groups: diabetic mellitus group (DM), metformin-treated group, low, medium, and high-dose CTP-treated group (CTP-L, CTP-M, and CTP-H). Normal mice served as the control group. After treatment for 28 days, body weight, fasting serum insulin (FSI), fasting blood glucose (FBG), homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were measured. Histological analysis of pancreatic tissue and immune organ indices was also performed to evaluate the anti-diabetes effect of CTP. SPSS (version 21.0) software was used for statistical analysis, and statistical differences were considered significant at p < 0.05. RESULTS: Compared with the DM group, the body weight and FSI level of CTP-H group increased by 36.13 and 32.47%, whereas the FBG and HOMA-IR decreased by 56.79 and 42.78%, respectively (p < 0.05). Histopathological examination of the pancreas revealed that CTP improved and repaired the impaired islet ß-cells in pancreatic tissue. Compared with the DM group, the levels of TC, TG, and LDL-C decreased by 13.84, 31.87, and 36.61%, whereas that of HDL-C increased by 28.60% in CTP-H (p < 0.05). Further study showed that the thymus index in CTP-H was elevated by approximately 54.96%, and the secretion of pro-inflammatory cytokines TNF-α, IL-6, and CRP was inhibited by approximately 19.97, 34.46, and 35.41%, respectively (p < 0.05). CONCLUSION: The anti-diabetes effect of CTP is closely associated with immunoregulation and anti-inflammation, and CTP may be considered as a therapeutic drug or functional food for DM intervention.


Assuntos
Cordyceps/química , Diabetes Mellitus Experimental/metabolismo , Polissacarídeos Fúngicos/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Polissacarídeos Fúngicos/química , Hipoglicemiantes/química , Hipolipemiantes/química , Masculino , Medicina Tradicional Chinesa , Camundongos , Estreptozocina
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