Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 764
Filtrar
1.
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
2.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505754

RESUMO

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


Assuntos
Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Lorazepam/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Acrilatos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Carragenina/química , Carragenina/farmacologia , Cromanos/química , Cromanos/farmacologia , Humanos , Hiperlipidemias/patologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidores de Lipoxigenase/farmacologia , Lorazepam/análogos & derivados , Ratos , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacologia
3.
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
4.
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
5.
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
6.
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
7.
Phytother Res ; 33(11): 2862-2869, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31423665

RESUMO

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings.


Assuntos
Angina Pectoris/tratamento farmacológico , Flores/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Extratos Vegetais/uso terapêutico , Zea mays/química , Angina Pectoris/sangue , China/epidemiologia , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Triglicerídeos/sangue
8.
Life Sci ; 234: 116753, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419445

RESUMO

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.


Assuntos
Acanthaceae/química , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipolipemiantes/química , Lipídeos/sangue , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar
9.
J Complement Integr Med ; 16(3)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318693

RESUMO

Background Antidiabetic activity of aqueous root extract of Strophanthus hispidus (SHP) was evaluated based on its folklore used in traditional medicine for the treatment of diabetes. Objectives: This study aimed to investigate the in-vitro and in-vivo antidiabetic potential of the aqueous root extract of SHP. Methods SHP (50, 100 and 200 mg/kg p.o.), glibenclamide (5 mg/kg p.o.), normal saline (10 mL/kg; diabetic control) and distilled water (10 mL/kg; normal control) were administered once daily for 28 days, with the measurement of fasting blood glucose level at 7 days interval. Blood samples were collected on day 28 for serum biochemical (albumin, total protein [TP], creatinine, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], triglycerides [TG], total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], bilirubin and urea) and hematological assays. The in-vitro antidiabetic activity was investigated using α-amylase and α-glucosidase enzymes inhibitory assays. Results SHP produced a day-dependent reduction in glucose level. Peak reduction (82.94 %; p < 0.05) was produced at the dose of 100 mg/kg. SHP significantly (p < 0.05) increased the level of HDL and TP but significantly (p < 0.05) reduced the levels of TG, LDL, TC, AST, ALT, ALP, bilirubin, creatinine and urea compared with diabetic control rats. Furthermore, SHP significantly (p < 0.05) increased the level of catalase, superoxide dismutase and reduced glutathione compared to diabetic control rats. SHP significantly (p < 0.05) inhibited α-amylase and α-glucosidase enzymes compared with acarbose. Conclusion The findings in this study showed that SHP possesses beneficial antidiabetic activity.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Strophanthus/química , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Antioxidantes/química , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Catalase/genética , Catalase/metabolismo , Diabetes Mellitus/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
10.
Food Funct ; 10(8): 4868-4876, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334540

RESUMO

In this study, a polysaccharide was extracted from Physalis pubescens L. (named PP). Its antihyperglycemic and antihyperlipidemic activities were evaluated in STZ-induced diabetic mice. Results showed that PP was determined to be composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glc) and galactose (Gal) with molar percentages of 4.65%, 17.34%, 1.43%, 6.24%, 5.52%, 45.5%, and 19.31%, respectively. The average molecular weight (Mw) was found to be 20.0 kDa. It had a strong α-glucosidase inhibitory activity in vitro. PP treatment could enhance the oral glucose tolerance, and increase the levels of SOD, GSH, CAT, vitamin C, vitamin E, HDL-c, C-peptide, GCK and hepatic glycogen in diabetic mice. Besides, PP treatment could also decrease the levels of MDA, TG, TC, LDL-c, BUN and G-6-Pase. The regulating effects were stronger in high dose PP treatment than those in the low and medium dose treatments. In short, PP played an important role in protecting STZ-induced diabetic mice, and the effect was closely related to its activities in antioxidation and regulating glucose and lipid metabolism.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Physalis/química , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Extratos Vegetais/química , Polissacarídeos/química , Estreptozocina
11.
Lipids Health Dis ; 18(1): 157, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351498

RESUMO

BACKGROUND: The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, ß-sitosterol ester with linoleic acids and ß-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. METHODS: Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with ß-sitosterol ester with linoleic acid, ß-sitosterol self-microemulsion, commercial ß-sitosterol health tablets and ß-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels . RESULTS: The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that ß-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. CONCLUSIONS: In this study, a new formulation of ß-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that ß-sitosterol self-microemulsion has a good blood lipid lowering effect.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Ácido Linoleico/farmacologia , Sitosteroides/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Fezes/química , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Lipídeos/sangue , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Sitosteroides/administração & dosagem , Sitosteroides/química , Comprimidos/administração & dosagem , Comprimidos/farmacologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-31233943

RESUMO

In the present study, a simple and efficient method based on orthogonal experimental design and macroporous resin chromatography was established for the first time for enrichment of polymethoxyflavones (PMFs) from the peels of Citrus reticulata 'Chachi' (CRC). The optimum conditions of extraction and enrichment process were as follows: use of a liquid to solid ratio of 1 to 14, two-hour extraction time repeated twice with 70% ethanol; use of HPD-450 macroporous resin, wash solvent of purified water and 25% aqueous ethanol, and 70% aqueous ethanol as desorption solvent. The purity of PMFs in the resulting extract reached 62.26%. Our data indicate that the PMFs purified could potently alleviate high-fat diet-induced hyperlipidaemia. The PMFs were nontoxic as determined by acute toxicity test. The method established was suitable for large-scale separation of PMFs from CRC peels and the PMFs might be developed as an anti-hyperlipidaemia agent or dietary supplement.


Assuntos
Cromatografia/métodos , Citrus/química , Flavonas/isolamento & purificação , Hipolipemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Animais , Feminino , Flavonas/administração & dosagem , Flavonas/química , Frutas/química , Humanos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química
13.
Phytomedicine ; 60: 152944, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178235

RESUMO

BACKGROUND: The seed of Trigonella foenum-graecum L. (Methika in Sanskrit) is a well known kaphahara (balancing kapha) herb in Ayurveda indicated in Prameha or early diabetes mellitus. It is also useful in obesity and reduces lipid level of blood. PURPOSE: We aimed to explore the metabolites present in the plant extract and to establish the combination synergy and the network pharmacology along with the underlying the mechanism of action involved. STUDY DESIGN: LC-MS/MS based metabolite screening followed by ADME screening and finally network pharmacology exploration of the mechanism of action involved against hyperlipidemia and hypolipidemia with neighbourhood based combination synergy approach. METHODS: Ethanolic extract of Trigonella foenum-graecum L. (TFHE) was subjected to LC-MS/MS analysis to identify the active constituents. Oral bioavailability and drug likeness was screened for all the compounds. Databases- Binding DB, DAVID, KEGG and STRING were used to gather information to develop the networks. The networks were constructed using Cytoscape 3.2.1. Combination synergy analysis was performed with the help of Cytoscape network analyzer tool with neighbourhood approach. RESULTS: The LC-MS/MS analysis identified 13 compounds which were found to be bio-available and drug like following the QED and Veber drug likeness parameters. The pathway analysis showed enrichment for different pathways like MAPK pathway (p-4.69E-07), JAK-STAT pathway (p-6.30E-05), Adipocytokine (p-0.00179), Type 2 Diabetes mellitus (0.00441), Insulin signalling pathway (p-0.0121), mTOR signalling pathway (p-0.000378), which are all connected to hyperlipidemia and hyperglycemia. The combination synergy network identified 23 targets interacting with 13 compounds based on a network neighbourhood approach. CONCLUSION: The network pharmacology analysis strongly suggested the multimode evidences that TFHE largely works on the insulin signalling pathway and mainly based on its antioxidant potential due to its interaction with carbonic anhydrase. Various compounds were found to be interacting with key proteins that activates EGFR/AKT/mTOR signalling cascade which has therapeutic implication in hyperglycemia and hyperlipidemia. The combination synergy network analysis based on neighbourhood approach can help us in further understanding mechanism of multi-molecular fixed dose combinations.


Assuntos
Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Trigonella/química , Antioxidantes/metabolismo , Disponibilidade Biológica , Células CACO-2 , Cromatografia Líquida , Diabetes Mellitus Tipo 2 , Etanol , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Insulina/metabolismo , Extratos Vegetais/química , Mapeamento de Interação de Proteínas , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem
14.
Regul Toxicol Pharmacol ; 107: 104404, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31199997

RESUMO

Hyperlipidemia is a serious health threat that has been linked to oxidative stress and systemic inflammation, causing among many other disorders essentially liver disease. The current study was conducted to evaluate the antihyperlipidemic, antioxidant and anti-inflammatory potential of methanol leaf extract from Erica multiflora (M-EML). Triton WR-1339-induced hyperlipidemic rats were divided into six groups: control group (CG), hyperlipidemic group (300 mg/kg body weight "BW") (HG), hyperlipidemic group treated with M-EML (150 and 250 mg/kg) (HG + M-EML), normal rats treated with M-EML (250 mg/kg) and fenofibrate-treated group (HG + FF) (65 mg/kg). After 24 h of administration, triton WR-1339 induced a significant increase in lipid profile, atherogenic index (AI) and Coronary Risk Index (CRI) in HG group compared to control group. Furthermore, triton WR-1339 administration induced alteration in the status of pro-inflammatory markers (aspartate transaminase, alanine transaminase, IFN-γ and Nitric oxide production). HG group showed also, a high level of lipid peroxidation, an altered antioxidant enzyme profiles and an increase in DNA damages, in liver. However, orally administration of M-EML mitigates significantly these disorders, proving hence a protective potential against triton WR-1339-induced hyperlipidemia. These findings suggest that M-EML extract could be used as functional foods and natural adjuvant treatment of hyperlipidemia.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ericaceae , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Fenofibrato/uso terapêutico , Hiperlipidemias/induzido quimicamente , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Folhas de Planta , Polietilenoglicóis , Ratos Wistar
15.
Molecules ; 24(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146427

RESUMO

Many publications have described the potential cardioprotective action of different medicinal plants, relating this effect with blood lipid levels. However, these publications do not justify the right amount of plant administered, which can vary greatly. Sideritis hyssopifolia is a little woody plant endemic to western and southwestern Europe. We have quantified its antioxidant activity, which can be used as an indicator of its cardioprotective action. This study evaluates the antioxidant capacity of Sideritis hyssopifolia to design a feed whose hypolipidemic effects are proven in cholesterol-fed New Zealand rabbits. Antioxidant action was assessed in infusions, which were prepared with 1 or 3 g of plant in 200 mL of water by using an ABTS assay and expressed as Ascorbic acid Equivalent Antioxidant Capacity (AEAC). Aqueous infusions with infusion times of 10 min and prepared with 3 g plant exhibited the strongest antioxidant activity. Sideritis hyssopifolia showed an intermediate antioxidant capacity for the concentrations and times of the infusion tested. According to our results, we suggest incorporating 2.36 g of S. hyssopifolia every 150 g of rabbit feeding stuff (15.73 g/kg). This chow decreased cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides levels in cholesterol-fed rabbits, as well as the atherogenic index. This reduction was similar to that obtained with simvastatin.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sideritis/química , Animais , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Lipídeos/sangue , Modelos Animais , Coelhos
16.
Int J Biol Macromol ; 134: 361-367, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31059740

RESUMO

In the present study, high-methoxyl pectin (HMP) was extracted from Hylocereus polyrhizus peel's using physico-chemical process. In addition, the hypolipidemic activity of HMP was investigated at different concentration and time corresponding to its adsorption ability. FTIR and contact angle analysis were used to determine the sorbent characterization. A high degree of esterification (63.8%) and the contact angle (95.5°) confirmed hydrophobic nature and resulting bad wetting of the HMP extract, respectively. The methoxyl content in the pectin acted as an affinity-precursor of the pectin towards cholesterol due to its increased hydrophobicity. The maximum equilibrium uptake capacity of cholesterol of 370.5mg/g (0.96mmol/g) was observed by HMP. The experimental data showed good fitting for Freundlich isotherm equation and followed pseudo-first-order kinetic model with a correlation coefficient (R2) of 0.89-0.97 due to physisorption mechanism. Intra-particle model confirmed that the cholesterol sorption rate by HMP was significantly influenced by external mass transfer (surface diffusion) and intra-particle diffusion (diffusion control). It was also revealed that the HMP extracted from Hylocereus polyrhizus peels possess a high affinity towards cholesterol, making it an ideal hypolipidemic agent.


Assuntos
Cactaceae/química , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Pectinas/química , Pectinas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Adsorção , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Esterificação , Interações Hidrofóbicas e Hidrofílicas , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Anal Bioanal Chem ; 411(15): 3257-3268, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31089788

RESUMO

It has been demonstrated that triterpenes in Alismatis rhizoma (Zexie in Chinese, ZX) contributed to the lipid-lowering effect on high-fat diet-induced hyperlipidemia. Alisol B 23-acetate, one of the abundant triterpenes in ZX, was used as the marker of quality control for ZX in Chinese Pharmacopoeia, while it could not reflect the lipid-lowering effect because other triterpenes in ZX also had prominent medicinal efficacy. To identify the significantly bioactive triterpenes in ZX, a multiple reaction monitoring (MRM)-based characteristic chemical profile (CCP)-support vector machine (SVM) model was used to explore the relationship between triterpenes and lipid-lowering effect of ZX. Firstly, the content of 87 targeted triterpenes was quantified by the MRM-based CCP using UHPLC-QTRAP-MS/MS. Secondly, the lipid-lowering effect of 30 ZX samples was assessed by 3T3-L1 preadipocytes. Thirdly, 9 of the 87 triterpenes possessing high mean impact value were identified to have significant lipid-lowering effect via the particle swarm-optimized SVM model. The new SVM model constructed by the 9 triterpenes showed good prediction performance and the overall prediction accuracy reached 81.94%. Finally, the real activity of these triterpenes was partly confirmed and was consistent with the prediction of SVM. These results showed that the method for discovery of triterpenes with prominent lipid-lowering activity in ZX was reliable. The proposed method is expected to provide an efficient and rapid approach for screening of active component and drug discovery in traditional herbs. Graphical abstract.


Assuntos
Alismataceae/química , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Rizoma/química , Máquina de Vetores de Suporte , Triterpenos/química , Triterpenos/farmacologia , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Animais , Cromatografia Líquida de Alta Pressão , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/análise , Camundongos , Espectrometria de Massas em Tandem
18.
Int J Biol Macromol ; 135: 706-716, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31129213

RESUMO

The aim of this work is to characterize the primary structure and physicochemical properties of natural polysaccharides (GLP) and degraded polysaccharides (GLPUD) from Ganoderma lucidum, and evaluate their hypolipidemic and antioxidant activities. The results of particle size distribution and scanning electron microscopy (SEM) showed that Ganoderma lucidum polysaccharides were effectively degraded by ultrasonic method. GLPUD was composed of the same monosaccharide units as GLP but with different molar ratios. Infrared spectra and NMR showed that the primary structure of polysaccharides had not been changed by ultrasonic degradation. Meanwhile, the thermal stability of polysaccharides increased after ultrasonic treatment. After administration by GLP and GLPUD four weeks, body weight, visceral index, atherosclerosis index (AI) and biochemical indicators in serum and in liver were determined. The results showed that GLPUD had stronger hypolipidemic and antioxidant activities than GLP. GLPUD was more effective than the GLP for reducing AI, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), raising high density lipoprotein (HDL-C) (p < 0.01), reducing malondialdehyde (MDA) content, as well as increasing the glutathione peroxidase (GSH-Px) in mice serum, increasing superoxide dismutase (SOD) activity and reducing MDA content in liver (p < 0.05 or p < 0.01). In addition, the histopathological observations of mice livers showed that GLPUD could significantly improve lipid metabolism disorder in hepatocytes. Thus, GLPUD might be tested as a more effective hypolipidemic drug.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Ganoderma/química , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Fenômenos Químicos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/sangue , Malondialdeído/metabolismo , Camundongos , Monossacarídeos/análise , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue , Ondas Ultrassônicas
19.
Int J Biol Macromol ; 134: 759-769, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100394

RESUMO

Reverse cholesterol transport (RCT) has been demonstrated to reduce hyperlipidemia, and fucoidans are found to possess hypolipidemic effect. This study was designed to investigate the lipid-lowering effect of the fucoidan from the brown seaweed A. nodosum and whether it improves RCT-related genes expression in C57 BL/6J mice. Our results indicated that fucoidan A3 (100 mg/kg/day) intervention significantly reduced plasma total cholesterol (~23.2%), triglyceride (~48.7%) and fat pad index. This fucoidan significantly increased the mRNA expression of low-density lipoprotein receptor (LDLR), scavenger receptor B type 1 (SR-B1), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), liver X receptor (LXR) ß, ATP-binding cassette transporter (ABC) A1 and sterol regulatory element-binding protein (SREBP) 1c, and decreased the expression of peroxisome proliferator-activated receptor (PPAR) γ, however, it had no effect on the expression of proprotein convertase subtilisin/kexin type 9, PPARα, LXRα, SREBP-2, ABCG1, ABCG8 and Niemann-Pick C1-like 1. These results demonstrated that this fucoidan improved lipid transfer from plasma to the liver by activating SR-B1 and LDLR, and up-regulated lipid metabolism by activating LXRß, ABCA1 and CYP7A1. In conclusion, this fucoidan lowers lipid by enhancing RCT-related genes expression, and it can be explored as a potential candidate for prevention or treatment of lipid disorders.


Assuntos
Ascophyllum/química , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/genética , Polissacarídeos/farmacologia , Alga Marinha/química , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Modelos Animais de Doenças , Hiperlipidemias/metabolismo , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Intestino Delgado/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/química , RNA Mensageiro , Receptores de LDL/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo
20.
Int J Biol Macromol ; 132: 922-928, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30930269

RESUMO

The lipid-lowering activities of chitosan (CS) and its quaternary ammonium salt (HACC) with two molecular weights (CS1, 2.5 × 105; HACC1, 2.4 × 105; CS2, 3.8 × 104; HACC2, 3.5 × 104) were evaluated for the rats fed with high-fat diets, respectively. The results showed that oral four CS samples resulted in the significant decrease of food efficiency ratio with the increase of fecal fat and cholesterol excretion (P < 0.05) compared with high-fat control group. Furthermore, the lipid-mediated oxidative stress and lipid levels in plasma and liver reduced, and hepatic lipase and lipoprotein lipase activities increased after the administration of CS and HACC. But the lipid-lowering effects of the four CS samples were different, which was HACC2 > HACC1 > CS2 > CS1 successively. The findings indicated that CS and HACC could reduce the absorption of dietary fat and cholesterol in vivo, which helped to alleviate hyperlipidemia and fatty liver effectively in the rats.


Assuntos
Quitosana/química , Quitosana/farmacologia , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Compostos de Amônio Quaternário/química , Animais , Quitosana/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/metabolismo , Hipolipemiantes/uso terapêutico , Lipase/sangue , Lipase/metabolismo , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA