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1.
J Environ Pathol Toxicol Oncol ; 38(3): 205-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679308

RESUMO

Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.


Assuntos
Artemisia/química , Fitoterapia , Extratos Vegetais/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Hipolipemiantes/farmacologia , Plantas Medicinais/química
2.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3335-3342, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602892

RESUMO

Based on pharmacodynamics-component correlation analysis,the best effective part of hyperlipidemia of Pericarpium Citri Reticulatae( PCR) was screened out to confirm the possible constituents with the lipid regulating effect,in order to provide a basis for the development of new drugs. Hyperlipidemia rats induced by fat emulsion were used to screen out the best hypolipidemic parts of PCR with TC,LDL-c as the index. HPLC-ESI-MS were used to analyze common constituents of the different solvent extracts from PCR. The constituents were classified and identified based on the retention time,m/z and UV spectra. And the HPLC-DAD were used to determine the contents of flavonoids( narirutin,hesperidin,didymin,nobiletin,tangeretin,3,5,6,7,8,3',4'-heptemthoxyflavone).Correlation analysis was conducted on the constituents and efficacy with the method of SPSS ANOVA bivariate correlation. Five extracts could significantly decrease the content of TC,LDL-c of hyperlipemia rats induced by fat emulsion,and the best effective part were95% ethanol and ethyl acetate. There were 19 common peaks in five different solvent extracts from PCR,and 17 flavonoids were identified and classified,including 10 polymethoxyflavonoids and 7 other flavonoids. According to the raw material quantity,the order of content of flavonones arranged from high to low: n-butyl alcohol part> 95% ethanol part> water part> ethyl acetate part> petroleum ether part; and the order of PMFs arranged from high to low: n-butyl alcohol part≈95% ethanol part≈ethyl acetate part > petroleum ether part > water part. The decreased percentage of TC,LDL-c was positively correlated with 10 common PMFs constituents,which suggested that PMFs may be the effective components for reducing blood lipid.


Assuntos
Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Hipolipemiantes/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Ratos
3.
Adv Exp Med Biol ; 1155: 87-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468388

RESUMO

The present study has investigated the effect of adding taurine (TAU) to a treatment of diabetes with metformin (MET), a hypoglycemic, and lovastatin (LOV), an antihyperlipidemic. To this end, male Sprague-Dawley rats, agent, 250-275 g in weight, were made diabetic with a single 60 mg/kg intraperitoneal (i.p.) dose of streptozocin (STZ) in 10 mM citrate buffer pH 4.5, and, after 14 days, treated daily with oral doses of MET (2.4 mM/kg), LOV (0.075 mM/kg) or TAU (2.4 mM/kg), and with binary and ternary combinations of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. In addition, rats receiving insulin (INS, 4 units/kg) by the subcutaneous route served as a reference treatment. All the rats were sacrificed on day 57 and their bloods collected into heparinized tubes. The corresponding plasma samples were analyzed for their glucose (GLC), insulin (INS), glycated hemoglobin (HbA1c), cholesterol (CHOL) and triglycerides (TG) contents. In comparison to normal rats, diabetic ones showed marked increases in GLC (+313%), HbA1c (+207%), CHOL (+66%) and TG (+188) and a profound decrease of INS levels (-76%) (p < 0.001 vs. control values). Among the various treatments, one with INS produced the greatest lowering effect on the plasm a GLC (+23%, p < 0.05), INS (+23%, p < 0.05) and TG (+3%), with the remaining changes being similar to those seen with MET. A treatment with MET reduced all the diabetic changes by at least threefold; and one with LOV had a significant (p < 0.001) lowering effect on the plasma CHOL and TG but was without an effect on the plasma GLC, INS and HbA1c. In common with LOV, TAU reduced the diabetic levels of both CHOL and TG and, in addition, reduced the diabetic plasma GLC and raised the corresponding INS level. Among binary combinations, one with LOV-MET provided a greater effect than MET alone only in terms of the plasma CHOL and TG; and one with LOV-TAU was only significantly better than TAU alone in lowering the TG levels. However, a treatment with LOV-MET-TAU led to reductions in all the plasma parameters examined that were much greater than those achieved with any of the individual agents or with their binary combinations (at p ≤ 0.05).


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lovastatina/farmacologia , Metformina/farmacologia , Taurina/farmacologia , Animais , Glicemia , Carboidratos/sangue , Hipolipemiantes/farmacologia , Insulina , Lipídeos/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina
4.
Biomed Khim ; 65(3): 227-230, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258146

RESUMO

The experimental study in vivo was aimed at evaluation of hypolipidemic action of the original natural microbial enzyme preparation of cholesterol oxidase (CHO). In preliminary chronic experiments in rats, rabbits, dogs, low toxicity, good tolerability, and anti-atherosclerotic activity of the CHO preparation were established. To assess the effect of CHO under conditions of moderate, nutritional, atherogenic dyslipoproteinemia, experiments were carried out in rats, guinea pigs, and rabbits. It was shown that administration of CHO had the pronounced lipid-lowering effect in models of atherogenic dyslipoproteinemia induced in these animals.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol Oxidase/farmacologia , Hipolipemiantes/farmacologia , Lipídeos/sangue , Animais , Cães , Cobaias , Coelhos , Ratos
5.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1911-1920, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342721

RESUMO

To study the binding capacity of active ingredients of Daidai lipid-lowering flavonoid extract and plasma protein,investigate the ways to improve the traditional formula for calculating protein binding rates based on ultrafiltration,and increase the stability and reliability of the experimental results. UPLC-MS/MS was used to establish a quantitative analysis method for simultaneous determination of active ingredients( neohesperidin and narngin) in ultrafiltrate. The protein binding rates were calculated by the traditional ultrafiltration formula. The correction factors( F) were introduced later,and the binding rates calculated with the correction factors were compared with those without the correction factors. The binding capacity of the extract and plasma protein was evaluated. The quantitative analysis method established by UPLC-MS/MS had a good specificity. The standard curve and linear range,method accuracy,precision and lower limit of quantitation all met the requirements. The method met the requirement for quantitative detection of the active ingredients in ultrafiltrate after the rat plasma was filtrated in the ultrafiltration tube. Under the experimental conditions,the binding rates of both active ingredients( neohesperidin and narngin) were higher than 90%. The active ingredients and rat plasma protein were bound in a concentration-dependent manner,with statistically significant differences( P<0. 01). There was no statistically significant difference between the protein binding abilities of the two active ingredients with rat plasma protein. Therefore,the active ingredients of Daidai lipid-lowering flavonoid extract had a relatively strong binding strength with rat plasma protein,and they were bound in a concentration-dependent manner. Additionally,when calculating protein binding rates by the traditional ultrafiltration formula,the correction factors could be introduced to effectively reflect the errors of multiple ingredient groups in traditional Chinese medicine extracts.This correction method could provide a reference thinking and practical reference for the improvement of the determination method of the traditional Chinese medicine plasma protein binding ability based on ultrafiltration.


Assuntos
Proteínas Sanguíneas , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Hipolipemiantes/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Lipídeos , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
6.
Adv Clin Exp Med ; 28(7): 931-936, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31237119

RESUMO

BACKGROUND: Fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) agonist, is used to treat patients with hypercholesterolemia and hypertriglyceridemia in order to reduce the risk of development of the atherosclerotic cardiovascular disease. However, it exerts pleiotropic effects beyond correcting atherogenic dyslipidemia to treat hypercholesterolemia. OBJECTIVES: The aim of this study was to investigate the potential effects of fenofibrate on endothelial function by analyzing the serum nitric oxide (NO) levels in patients with hypertriglyceridemia. MATERIAL AND METHODS: Lipid profiles and serum NO levels were assessed in 56 healthy adults aged 29 to 84 years, before and after 12 weeks of fenofibrate (250 mg/d; n = 30) or placebo (n = 26). Appropriate dietary suggestions for hypertriglyceridemia were made for all patients. This study was randomized, double-blind and placebo-controlled in design. RESULTS: Total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglyceride levels significantly decreased; high-density lipoprotein (HDL) and NO levels significantly increased after 12 weeks of fenofibrate therapy. We observed a statistically significant correlation between the increase in serum NO levels and decrease in serum triglyceride levels (r = -0.42, p = 0.02) in the fenofibrate group. CONCLUSIONS: The positive effect of short-term fenofibrate treatments on vascular endothelial functions in patients with hypertriglyceridemia has been demonstrated by increasing the serum NO levels. Agents such as fenofibrate targeting PPARα-associated signaling pathways show promise as an alternative treatment of vascular dysfunction related to advanced age and hyperlipidemia.


Assuntos
Fenofibrato/efeitos adversos , Fenofibrato/farmacologia , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacologia , Óxido Nítrico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Fenofibrato/uso terapêutico , Humanos , Hipolipemiantes/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Triglicerídeos
7.
Carbohydr Polym ; 219: 181-190, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151515

RESUMO

Water-soluble fraction (WSF), CDTA-soluble fraction (CSF), sodium carbonate-soluble fraction (SSF), loosely-bonding KOH-soluble fractions (LKF) and tightly-bonding KOH-soluble fractions (TKF) were sequentially extracted from tomato cell wall polysaccharides. Physicochemical properties and functional bioactivities of these different bonding state tomato fruit polysaccharides (DBTP) were investigated. WSF, CSF and SSF were identified as pectic polysaccharides, while LKF and TKF were identified as hemicellulose. WSF, possessing plenty of galacturonic acids, was considered as an aggregative of linear homogalacturonan with extremely high molecular weight. CSF and SSF, rich in neutral sugars side chains, contained abundant rhamnogalacturonan regions. These polysaccharides exhibited distinct surface morphology and special FTIR spectrums. Thermal analysis manifested that LKF and TKF exhibited higher thermal stability. WSF and SSF showed higher apparent viscosity and elasticity. Assays for functional bioactivities suggested that CSF and SSF displayed stronger antioxidant activities, while CSF, SSF and TKF exhibited higher hypolipidemic activities.


Assuntos
Parede Celular/química , Frutas , Lycopersicon esculentum , Polissacarídeos , Antioxidantes/farmacologia , Elasticidade , Frutas/citologia , Frutas/metabolismo , Hipolipemiantes/farmacologia , Lycopersicon esculentum/citologia , Lycopersicon esculentum/metabolismo , Pectinas/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Solubilidade , Viscosidade
8.
Altern Ther Health Med ; 25(4): 54-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31202212

RESUMO

Alcohol catabolism produces oxidative stress, causing cell death and inflammation in liver tissue principally. Hawthorn (Crataegus oxyacantha) and Rosemary (Rosmarinus officinalis) are medicinal plants that have shown a potent antioxidant activity related with anti-inflammatory properties. The objective of this study was the evaluation of Hawthorn and Rosemary methanol extracts as preventive treatment in alcoholic liver disease (ALD). ALD rat model was used to measure serum hepatic enzyme levels (AST, ALT, γ-GT and ACP), total bilirubin, liver glycogen, lipid peroxidation, total antioxidant capacity (TAC) and serum lipid profile (total cholesterol, triglycerides, LDL and HDL) as well as histopathological analysis in hepatic tissues was recorder. Phytotreatments showed preventive effect, decreasing AST, γ-GT, lipid peroxidation and bilirubin indictors while TAC and liver glycogen stores increase. Interestingly, Rosemary diminished the levels of ALT and ACP. Remarkable both treatments show liver tissue damage reduction. Hawthorn proved antihyperlipidemic effect, eviting increase in all lipid indicators, while Rosemary showed antihyperlipidemic effect only in LDL levels without affecting HDL levels. The results indicate that Hawthorn and Rosemary treatments have different mechanisms of action; however they show hepatoprotective effect against ALD in rat model. Hawthorn and Rosemary could be used to prevent or help in the treatment of ALD.


Assuntos
Antioxidantes/farmacologia , Crataegus/química , Hipolipemiantes/farmacologia , Hepatopatias Alcoólicas/tratamento farmacológico , Fígado/efeitos dos fármacos , Rosmarinus/química , Animais , Antioxidantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Fígado/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
9.
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
10.
Phytomedicine ; 59: 152896, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978649

RESUMO

BACKGROUND: The selection of active compounds for the quality evaluation of traditional Chinese medicine (TCM), specifically complex formulas, remains a challenge for researchers, as components selected as indexes usually have no clear relation with the therapeutic effects of interest. As a suggested resolution, quality control markers (Q-markers) showed good perspective for discriminating numerous compounds found for specific efficacies. In the presented study, the components of the Yinlan (YL) capsule, a TCM patent formula comprising four ingredients, were evaluated and selected for their lipid regulatory effects using principles for Q-marker selection. PURPOSE: The mechanism of TCM therapeutic effects involves several pathways and targets that combine to become an integrated action in the body. Therefore, it is assumed that specific compounds in YL should have good affinity for related targets and obvious effects (both up- and downregulating). Thus, a series of experiments, including cytobiology, animal-based pharmacodynamics, computer-assisted drug design, conventional content determination and pharmacokinetics, would be helpful for the selection and final confirmation of Q-markers. METHODS: The capsule was first administered to Wistar mice fed a high-fat diet and tested for their triglycerides (TG) and total cholesterol (TC) values to evaluate the effectiveness of YL. Then, liver tissue was extracted for gene expression. According to the results, the compounds in YL with good affiliation were selected and determined using UHPLC-MS-MS, and those with adequate results in the capsule were chosen as Q-marker candidates. Finally, pharmacokinetics research was performed; the candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of YL. RESULTS: YL capsule was capable of lowering TG and TC levels. For target selection, the expression of LXR mRNA increased significantly at all three tested dosages. Downstream genes, such as LCAT, CYP7A1, and ABCA1, and intestinal FXR mRNA also showed significant increases in expression. For screening of the Q-marker candidates, 5 compounds were selected according to abovementioned results. The pharmacokinetics research demonstrated that the rats exploited lupeol and ginsenoside Rb3 in a desirable pattern with adequate bioavailability, which confirmed their roles as lipid regulatory Q-markers. CONCLUSION: The YL capsule was demonstrated to have obvious lipid regulatory effects, which are mainly exerted by targeting LXR and its related pathway. Lupeol and ginsenoside Rb3 were validated as Q-markers that represent the anti-hyperlipidemia activity of the capsule.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Receptores X do Fígado/metabolismo , Animais , Biomarcadores/análise , Cápsulas , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/análise , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacocinética , Hiperlipidemias/etiologia , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/genética , Camundongos , Triterpenos Pentacíclicos/farmacocinética , Controle de Qualidade , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Triglicerídeos/sangue
11.
Arh Hig Rada Toksikol ; 70(1): 30-35, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30956215

RESUMO

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14-17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.


Assuntos
Encéfalo/efeitos dos fármacos , Butirilcolinesterase/efeitos dos fármacos , Butirilcolinesterase/metabolismo , Fenofibrato/farmacologia , Hiperlipidemias/tratamento farmacológico , Fígado/efeitos dos fármacos , Plasma/efeitos dos fármacos , Sinvastatina/farmacologia , Animais , Anticolesterolemiantes/farmacologia , Encéfalo/metabolismo , Hipolipemiantes/farmacologia , Fígado/metabolismo , Plasma/metabolismo , Ratos , Ratos Wistar/metabolismo
12.
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
13.
Mol Cell Biochem ; 458(1-2): 39-47, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30905023

RESUMO

The development of new antihyperlipidemic agents with higher potency and lower side effects is of high priority. In this study, 1,3,4 thiadiazole Schiff base derivatives were synthesized as potential peroxisome proliferation-activated receptor-α (PPARα) agonists and characterized using elemental analysis, FTIR, 1H-NMR, 13C-NMR and mass spectroscopy and then tested for their hypolipidemic activity in Triton WR-1339-induced acute hyperlipidemic rat model in comparison with bezafibrate. The compounds showed significant hypolipidemic activity. Induced fit docking showed that the compounds are potential activators of PPARα with binding scores - 8.00 Kcal/mol for 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole. PCR array analysis showed an increase in the expression of several genes involved in lipid metabolism through mitochondrial fatty acid ß oxidation and are part of PPARα signaling pathway including Acsm3, Fabp4 and Hmgcs1. Gene expression of Lrp12 and Lrp1b involved in LDL uptake by liver cells and Cyp7a1 involved in cholesterol catabolism were also found to be upregulated.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes , PPAR alfa/agonistas , Tiadiazóis , Doença Aguda , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , PPAR alfa/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tiadiazóis/química , Tiadiazóis/farmacocinética , Tiadiazóis/farmacologia
14.
Int J Biol Macromol ; 131: 81-88, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851330

RESUMO

Polysaccharide from Grifola frondosa 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 Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ±â€¯0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were OH and CN groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P < 0.01). These results suggest that GFP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.


Assuntos
Cromo/química , Polissacarídeos Fúngicos/química , Grifola/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Análise Espectral , Estreptozocina/efeitos adversos
15.
Pak J Pharm Sci ; 32(1(Special)): 383-389, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852474

RESUMO

.This study aimed to investigate the hypolipidemic and antioxidant activities of volatile oils from Michelia martini Levl. The antioxidant property of volatile oils from Michelia martini in vitro was investigated by establishment of various systems. High fat diet induced rats were used to assess the hypolipidemic and antioxidant activities of Michelia martini volatile oils in vivo. The level of total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alanine transaminase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase in serum, and the activities of catalase, malondialdehyde, super oxide dismutase and glutathione in liver of rats were assayed by standard procedures. Our results showed that Michelia martini exhibits strong hypolipidemic and antioxidant activities both in vitro and vivo. Our data were also supplemented with histopathological studies on liver tissues and aorta sections of rats.


Assuntos
Antioxidantes/farmacologia , Hipolipemiantes/farmacologia , Magnoliaceae/química , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Anfotericina B/toxicidade , Animais , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Células CHO , Cricetulus , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Hiperlipidemias/sangue , Hiperlipidemias/prevenção & controle , Hipolipemiantes/isolamento & purificação , Lipídeos/sangue , Masculino , Óleos Voláteis/isolamento & purificação , Picratos/química , Folhas de Planta/química , Óleos Vegetais/isolamento & purificação , Ratos Sprague-Dawley
16.
N Engl J Med ; 380(11): 1033-1042, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30865797

RESUMO

BACKGROUND: ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear. METHODS: We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer. RESULTS: A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval [CI], 0.78 to 0.87; P = 4.0×10-14) for the ACLY score and 0.836 (95% CI, 0.81 to 0.87; P = 3.9×10-19) for the HMGCR score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer. CONCLUSIONS: Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.).


Assuntos
ATP Citrato (pro-S)-Liase/genética , Doenças Cardiovasculares/genética , LDL-Colesterol/sangue , Predisposição Genética para Doença , Hidroximetilglutaril-CoA Redutases/genética , Análise da Randomização Mendeliana , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Diabetes Mellitus/genética , Ácidos Dicarboxílicos/farmacologia , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/farmacologia , Ácidos Graxos/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Lipoproteínas/sangue , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Neoplasias/genética , Razão de Chances , Risco , Triglicerídeos/sangue
17.
Molecules ; 24(5)2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30857274

RESUMO

A series of novel caffeoylquinic acid derivatives of chlorogenic acid have been designed and synthesized. Biological evaluation indicated that several synthesized derivatives exhibited moderate to good lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 3d, 3g, 4c and 4d exhibited more potential lipid-lowering effect than the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 3d, 3g, 4c and 4d revealed that the lipid-lowering effects were related to their regulation of TG levels and merit further investigation.


Assuntos
Hipolipemiantes/síntese química , Hipolipemiantes/farmacologia , Ácido Oleico/farmacologia , Ácido Quínico/análogos & derivados , Ácido Clorogênico/farmacologia , Células Hep G2 , Humanos , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Sinvastatina/farmacologia
18.
Int J Biol Macromol ; 129: 422-432, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30742925

RESUMO

The structure, antioxidant and anti-hyperlipidemic activities of polysaccharides from Nitraria retusa fruits (named as NRFP) were investigated. The NRFP fraction, with a molecular weight of 66.5 kDa, was composed of a ß-(1 → 3)-glucan, containing neutral sugars (69.1%) but also uronic acids up to 23.1% due to pectin structure. The monosaccharide composition highlighted a polymer composed of glucose (41.4%), galacturonic acid (30.5%), galactose (12.6%), arabinose (11.8%) and rhamnose (3.70%). In the antioxidant assays, NRFP exhibited effective total antioxidant capacity (IC50 = 7.82 mg/ml), scavenging activities on DPPH radical (IC50 = 0.87 mg/ml) and hydrogen peroxide (IC50 = 2.03 mg/ml). In addition, NRFP proved protective effects on H2O2 induced hemolysis (IC50 = 66.2 µg/ml). In vivo NRFP reduced the hyperlipidemia, hepatotoxicity, cardiovascular and coronary diseases induced by Triton X-100.


Assuntos
Frutas/química , Magnoliopsida/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Água/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Aterosclerose/sangue , Biomarcadores/sangue , Cardiotônicos/química , Cardiotônicos/farmacologia , Cardiotônicos/toxicidade , Citoproteção/efeitos dos fármacos , Glicosilação , Coração/efeitos dos fármacos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Hipolipemiantes/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas/sangue , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Monossacarídeos/análise , Polissacarídeos/toxicidade , Solubilidade
19.
Int J Biol Macromol ; 129: 281-292, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30708002

RESUMO

In the present work, we investigated the anti-hyperlipidemic, antioxidant and organic protection effects of acidic-extractable Dictyophora indusiata polysaccharides (Ac-DPS) on hyperlipidemic mice induced by high-fat emulsion. The results demonstrated that Ac-DPS had impressive abilities to mitigate oxidative stress by increasing the activities of antioxidant enzyme and reducing the contents of lipid peroxide. Moreover, lipid levels in serum were returned to normal status. Besides, Ac-DPS exhibited potential hepatic and renal protection effects reflected by decreasing serum enzyme activities, lowering TBIL, UREA and CREA levels and increasing ALB content. At the same time, histopathological observations proved protective effects of Ac-DPS on organs. Subsequently, the physical properties of polysaccharide were also investigated by HPGPC and FT-IR. The above consequences confirmed the important role of Ac-DPS as a functional food and natural medicine in the fight against oxidative stress and the prevention of hyperlipidemia.


Assuntos
Antioxidantes/farmacologia , Basidiomycota/química , Polissacarídeos Fúngicos/farmacologia , Hipolipemiantes/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/química , Biomarcadores , Polissacarídeos Fúngicos/química , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Peso Molecular , Substâncias Protetoras/química , Análise Espectral
20.
Int J Biol Macromol ; 129: 316-325, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30708004

RESUMO

The aims of this work were to extract the enzymatic residue polysaccharides (EnRPS) from Pleurotus ostreatus and investigate the antioxidant and anti-hyperlipidemic effects on high-fat-high-cholesterol emulsion (HFHCE)-induced liver injured mice. The results revealed that EnRPS at 400 mg/kg bw showed superior liver protective effects by ameliorating the AI, lowing the hepatic MPO, FFA, ADPN, TC and TG indicators, and improving the antioxidant status by enhancing liver enzyme activities (SOD, CAT, LEP, INS and T-AOC), eliminating the MDA content, decreasing the levels of LDL-C, TC, TG, ALT, AST and ALP, and increasing the HDL-C in serum. And in addition, GC, FTIR, NMR and pathological sections were also studied. The above consequences suggested that EnRPS could be used as functional foods of oxidative stress and anti-hyperlipidemic against liver injury.


Assuntos
Polissacarídeos Fúngicos/farmacologia , Hipolipemiantes/farmacologia , Pleurotus/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Biomarcadores , Polissacarídeos Fúngicos/química , Teste de Tolerância a Glucose , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Análise Espectral , Testes de Toxicidade Aguda
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