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1.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
2.
Medicine (Baltimore) ; 98(34): e16931, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441882

RESUMO

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94-0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45-1.62), 0.63 (95% CI, 0.57-0.71), and 0.34 (95% CI, 0.30-0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.


Assuntos
Cognição/efeitos dos fármacos , Demência/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Demência/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia
3.
BMC Complement Altern Med ; 19(1): 129, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196040

RESUMO

BACKGROUND: Green tea has polyphenols like flavonoids and catechins; mainly epigallocatechin-3-gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC), out of which EGCG is of higher abundance. EGCG has shown preventive role in hypercholesterolemia. However, due to low oral bioavailability, a need arises to improve its membrane permeability and transporter-mediated intestinal efflux. Therefore, an attempt was made to enhance permeability and bioavailability of EGCG using curcumin to treat hyperlipidemia. Further, it was formulated in herbal tea bags to achieve patient compliance. METHODS: EGCG extracted from green tea leaves was confirmed by High Performance Thin Layer Chromatography. Green tea extract (GTE), curcumin and their mixtures were subjected to Fourier Transform Infra-Red spectroscopy and Differential Scanning Calorimetry for compatibility studies. Powder formulation was prepared comprising GTE, curcumin, sucralose and cardamom. RESULTS: Ex-vivo study was performed on everted goat intestine, analyzed by HPLC and demonstrated highest permeation of GTE:curcumin (220:50) (53.15%) than GTE (20.57%). Antihyperlipidemic activity was performed in rats for 15 days. Blood sample analysis of rats of test groups (formulation and GTE solution) fed on high fat diet showed (mg/dl):cholesterol 80 and 90, triglycerides 73.25 and 85.5, HDL 50.75 and 46, LDL 43.9 and 46, VLDL 14.65 and 17.1 respectively with significant lipid regulating effect. CONCLUSION: Curcumin enhanced permeability of EGCG. Therefore, P-glycoprotein pump inside intestine can be potential mechanism to enhance permeability of EGCG. Thus, EGCG-curcumin herbal tea bag is promising nutraceutical to treat hyperlipidemia in day-to-day life achieving patient compliance.


Assuntos
Antioxidantes/farmacocinética , Catequina/análogos & derivados , Curcumina/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Masculino , Permeabilidade , Fitoterapia , Ratos Sprague-Dawley , Chá
4.
J Agric Food Chem ; 67(26): 7325-7335, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184120

RESUMO

Tea polyphenols (TP) possess the ability to regulate dyslipidemia and gut microbiota dysbiosis. However, the underlying mechanism is still elusive. The present study explored the intervention of TP on high fat diet induced metabolic disorders, gut microbiota dysbiosis in mice, and the underlying intestinal mechanism. As a result, TP significantly ameliorated hyperlipidemia, improved the expression levels of hepatic lipid metabolism genes, and modulated gut microbiota. The underlying mechanism was supposed to rely on the maintaining of intestinal redox state by TP. Intestinal redox related indicators were significantly correlated with the distribution of gut microbiota. An unidentified genus of Lachnospiraceae, Bacteroides, Alistipes, and Faecalibaculum were identified as the biomarkers for intestinal redox state. Importantly, different dosages of TP modulated intestinal redox state and gut microbiota in varied patterns, and an overdose intake attenuated the beneficial effects on gut health. Our findings offered novel insights into the mechanism of TP on intestinal homeostasis.


Assuntos
Camellia sinensis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Intestinos/microbiologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Chá
7.
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
8.
BMC Bioinformatics ; 20(Suppl 7): 201, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074378

RESUMO

BACKGROUND: A key problem in systems biology is the determination of the regulatory mechanism corresponding to a phenotype. An empirical approach in this regard is to compare the expression profiles of cells under two conditions or tissues from two phenotypes and to unravel the underlying transcriptional regulation. We have proposed the method BASE to statistically infer the effective regulatory factors that are responsible for the gene expression differentiation with the help from the binding data between factors and genes. Usually the protein-DNA binding data are obtained by ChIP-seq experiments, which could be costly and are condition-specific. RESULTS: Here we report a definition of binding strength based on a probability model. Using this condition-free definition, the BASE method needs only the frequencies of cis-motifs in regulatory regions, thereby the inferences can be carried out in silico. The directional regulation can be inferred by considering down- and up-regulation separately. We showed the effectiveness of the approach by one case study. In the study of the effects of polyunsaturated fatty acids (PUFA), namely, docosahexaenoic (DHA) and eicosapentaenoic (EPA) diets on mouse small intestine cells, the inferences of regulations are consistent with those reported in the literature, including PPARα and NFκB, respectively corresponding to enhanced adipogenesis and reduced inflammation. Moreover, we discovered enhanced RORA regulation of circadian rhythm, and reduced ETS1 regulation of angiogenesis. CONCLUSIONS: With the probabilistic definition of cis-trans binding affinity, the BASE method could obtain the significances of TF regulation changes corresponding to a gene expression differentiation profile between treatment and control samples. The landscape of the inferred cis-trans regulations is helpful for revealing the underlying molecular mechanisms. Particularly we reported a more comprehensive regulation induced by EPA&DHA diet.


Assuntos
Indutores da Angiogênese/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Regulação da Expressão Gênica , Hiperlipidemias/genética , Motivos de Nucleotídeos , Transcrição Genética , Adipogenia/efeitos dos fármacos , Animais , Hiperlipidemias/tratamento farmacológico , Intestino Delgado/metabolismo , Camundongos , Regiões Promotoras Genéticas
9.
J Manag Care Spec Pharm ; 25(5): 544-554, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31039062

RESUMO

BACKGROUND: Statins are effective in helping prevent cardiovascular disease (CVD). However, studies suggest that only 20%-64% of patients taking statins achieve reasonable low-density lipoprotein cholesterol (LDL-C) thresholds. On-treatment levels of LDL-C remain a key predictor of residual CVD event risk. OBJECTIVES: To (a) determine how many patients on statins achieved the therapeutic threshold of LDL-C < 100 mg per dL (general cohort) and < 70 mg per dL (secondary prevention cohort, or subcohort, with preexisting CVD); (b) estimate the number of potentially avoidable CVD events if the threshold were reached; and (c) forecast potential cost savings. METHODS: A retrospective, longitudinal cohort study using electronic health record data from the Indiana Network for Patient Care (INPC) was conducted. The INPC provides comprehensive information about patients in Indiana across health care organizations and care settings. Patients were aged > 45 years and seen between January 1, 2012, and October 31, 2016 (ensuring study of contemporary practice), were statin-naive for 12 months before the index date of initiating statin therapy, and had an LDL-C value recorded 6-18 months after the index date. Subsequent to descriptive cohort analysis, the theoretical CVD risk reduction achievable by reaching the threshold was calculated using Framingham Risk Score and Cholesterol Treatment Trialists' Collaboration formulas. Estimated potential cost savings used published first-year costs of CVD events, adjusted for inflation and discounted to the present day. RESULTS: Of the 89,267 patients initiating statins, 30,083 (33.7%) did not achieve the LDL-C threshold (subcohort: 58.1%). In both groups, not achieving the threshold was associated with patients who were female, black, and those who had reduced medication adherence. Higher levels of preventive aspirin use and antihypertensive treatment were associated with threshold achievement. In both cohorts, approximately 64% of patients above the threshold were within 30 mg per dL of the respective threshold. Adherence to statin therapy regimen, judged by a medication possession ratio of ≥ 80%, was 57.4% in the general cohort and 56.7% in the subcohort. Of the patients who adhered to therapy, 23.7% of the general cohort and 50.5% of the subcohort had LDL-C levels that did not meet the threshold. 10-year CVD event risk in the at-or-above threshold group was 22.78% (SD = 17.24%) in the general cohort and 29.56% (SD = 18.19%) in the subcohort. By reducing LDL-C to the threshold, a potential relative risk reduction of 14.8% in the general cohort could avoid 1,173 CVD events over 10 years (subcohort: 15.7% and 454 events). Given first-year inpatient and follow-up costs of $37,300 per CVD event, this risk reduction could save about $1,455 per patient treated to reach the threshold (subcohort: $1,902; 2017 U.S. dollars) over a 10-year period. CONCLUSIONS: Across multiple health care systems in Indiana, between 34% (general cohort) and 58% (secondary prevention cohort) of patients treated with statins did not achieve therapeutic LDL-C thresholds. Based on current CVD event risk and cost projections, such patients seem to be at increased risk and may represent an important and potentially preventable burden on health care costs. DISCLOSURES: Funding support for this study was provided by Merck (Kenilworth, NJ). Chase and Boggs are employed by Merck. Simpson is a consultant to Merck and Pfizer. The other authors have nothing to disclose.


Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/economia , LDL-Colesterol/efeitos dos fármacos , Redução de Custos/estatística & dados numéricos , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Hiperlipidemias/sangue , Hiperlipidemias/economia , Indiana , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
J Agric Food Chem ; 67(20): 5782-5791, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31055921

RESUMO

Reverse cholesterol transport (RCT) is a physiological process, in which excess peripheral cholesterol is transported to the liver and further excreted into the bile and then feces. Recently, fucoidans are reported to have a lipid-lowering effect. This study was designed to investigate whether fucoidan from the brown seaweed Ascophyllum nodosum lowers lipid by modulating RCT in C57BL/6J mice fed a high-fat diet. Our results indicated that fucoidan intervention significantly reduced plasma triglyceride, total cholesterol, and fat pad index and markedly increased high-density lipoprotein cholesterol in a dose-dependent manner. In the liver, fucoidan significantly increased the expression of peroxisome proliferator-activated receptor (PPAR)α, PPARγ, liver X receptor (LXR)ß, adenosine triphosphate (ATP) binding cassette (ABC)A1, ABCG8, low-density lipoprotein receptor (LDLR), scavenger receptor B type 1 (SR-B1), and cholesterol 7-α-hydroxylase A1 (CYP7A1) and decreased the triglyceride level and expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and PPARß but had no effect on LXRα, ABCG1, and ABCG5. In the small intestine, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and improved ABCG5 and ABCG8. These results demonstrated that fucoidan can improve lipid transfer from plasma to the liver by activating SR-B1 and LDLR and inactivating PCSK9 and upregulate lipid metabolism by activating PPARα, LXRß, ABC transporters, and CYP7A1. In the small intestine, this fucoidan can decrease cholesterol absorption and increase cholesterol excretion by activating NPC1L1 and ABCG5 and ABCG8, respectively. In conclusion, fucoidan from A. nodosum may lower lipids by modulating RCT-related protein expression and can be explored as a potential compound for prevention or treatment of hyperlipidemia-related diseases.


Assuntos
Ascophyllum/química , Colesterol/metabolismo , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Alga Marinha/química , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de LDL/genética , Receptores de LDL/metabolismo , Receptores Depuradores/genética , Receptores Depuradores/metabolismo
11.
Expert Opin Drug Saf ; 18(7): 611-621, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31100030

RESUMO

INTRODUCTION: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. Lipid-lowering therapy is a cornerstone of the CV risk modification strategy. The first line treatment for hyperlipidemia is statins, which decrease low-density lipoprotein cholesterol (LDL-C) by 30-50% and proportionally reduce the CV events. However, they are not always enough to achieve LDL-C goals in many patients, and some patients are statin intolerant. For this reason, new powerful injectable lipid-lowering drugs have been developed. AREAS COVERED: The aim of this narrative review was to summarize the more recent clinical data on safety and tolerability of injectable lipid-lowering drugs. After an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocumab), small interfering RNA molecule inclisiran, antisense oligonucleotides (mipomersen, volanesorsen, ISIS 681257), and drugs targeting angiopoietin-like protein 3 (evinacumab, IONIS-ANGPTL3Rx). EXPERT OPINION: Injectable lipid-lowering therapy for patients at high risk for CV disease complications or with severe inherited hypercholesterolemias can be an important element of the available therapeutic armamentarium. Clinical data prove the favorable risk-benefit profile of evolocumab, alirocumab, and inclisiran. Mipomersen, volanesorsen, ISIS 681257, evinacumab, and IONIS-ANGPTL3Rx safety is currently less extensively studied, especially in patients with comorbidities and polypharmacotherapy.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Animais , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipidemias/complicações , Hipolipemiantes/efeitos adversos , Injeções , Fatores de Risco
12.
Medicine (Baltimore) ; 98(18): e15502, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045838

RESUMO

BACKGROUND: The aim of this meta-analysis was to understand the relationship between statin with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). METHODS: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, Chinese Medical and Biological Literature Database, China HowNet, Vip, and Wanfang. We calculated pooled odds ratios (OR) and 95% CI and standardized mean difference (SMD). Using Stata 12.0 and Review 5.3 for meta-analysis. RESULTS: This meta-analysis included 11 articles and 49,128 participants. Results show statins could not reduce the incidence of BPH [OR = 0.77 (0.57, 1.03, P = .08]. For patients over 60 years old, statins could reduce the incidence of BPH [OR = 0.35 (0.22, 0.55), P < .0001]. Statins can slow down the progression of LUTS in BPH [SMD = -0.32 (-0.54, -0.10), P = .004], but there is no significant correlation between them in patients taking drugs for less than 1 year. CONCLUSION: Statins have no significant effect on the incidence of BPH, but statins can reduce the risk of BPH for patients over 60 years old. For patients with hyperlipidemia, the duration of medication is more than 1 year, which can slow down the progression of LUTS. However, more high-quality and large sample size studies are needed to further improve and verify.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Sintomas do Trato Urinário Inferior/induzido quimicamente , Hiperplasia Prostática/induzido quimicamente , Idoso , China/epidemiologia , Humanos , Incidência , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/epidemiologia , Fatores de Risco , Fatores de Tempo
13.
Complement Ther Med ; 43: 218-226, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935534

RESUMO

Hyperlipidemia is rampant as a crucial risk factor for cardiovascular diseases. Xue Fu Zhu Yu (XFZY), a prescription formula in traditional Chinese medicine, is well-known for treating hyperlipidemia. Herein we conducted meta-analysis and assessed the efficacy of XFZY prescription as mono or adjunctive therapy in patients with hyperlipidemia. Databases including Medline, Cochrane Library, Embase, CNKI, Wanfang Data and VIP Information were comprehensively investigated via searching keywords "Xuefuzhuyu", "Xuefu Zhuyu", "Xue Fu Zhu Yu", "Xuefu-Zhuyu" or "XFZY" in combination with "hyperlipidemia" and "dyslipidemia". Efficacy, methodological quality, and publication bias of recruited trials on XFZY prescription were also assessed. Review Manager version 5.3 software was used for statistical analysis. Twelve trials involving 1305 participants all reported in Chinese were enrolled and, based on our analysis, significant increase of efficacy in XFZY prescription groups compared to control groups was observed, and there was either significance or non-significance of differences in regulating the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). This meta-analysis preliminarily demonstrated that XFZY prescription is effective for treating hyperlipidemia, but due to the poor methodological quality of most analyzed trials, conclusion should be cautiously summarized. Thoroughly designed, large-scale and multicenter trials are needed to estimate efficacy and safety of XFZY prescription for hyperlipidemia in the future.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Adolescente , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue , Adulto Jovem
14.
Molecules ; 24(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939835

RESUMO

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Metaboloma/efeitos dos fármacos , Saponinas/farmacologia , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Masculino , Filogenia , Ratos , Ratos Sprague-Dawley
15.
Nutrients ; 11(4)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935037

RESUMO

The aim of this study was to investigate the effect of melatonin on hepatic lipid metabolism in hamsters with high-fat diet (HFD)-induced dyslipidemia. Male Syrian hamsters were kept on either a chow control (C) or HFD for four weeks. After four weeks, animals fed the HFD were further randomly assigned to four groups: high-fat only (P), melatonin low-dosage (L), medium-dosage (M), and high-dosage (H) groups. The L, M, and H groups, respectively, received 10, 20, and 50 mg/kg/day of a melatonin solution, while the P and C groups received the ethanol vehicle. After eight weeks of the intervention, results showed that a low dose of melatonin significantly reduced HFD-induced hepatic cholesterol and triglycerides; decreased plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol; and increased plasma high-density lipoprotein cholesterol (p < 0.05). In addition, melatonin markedly decreased activities of the hepatic lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) (p < 0.05), and elevated the relative hepatic carnitine palmitoyltransferase-1α expression in hamsters with HFD-induced hyperlipidemia. Consequently, melatonin reduced activities of the hepatic lipogenic enzymes, ACC and FAS. In summary, chronic melatonin administration improved HFD-induced dyslipidemia and hepatic lipid accumulation in Syrian hamsters with HFD-induced dyslipidemia, which might have occurred through inhibiting the lipogenesis pathway.


Assuntos
Antioxidantes/farmacologia , Hiperlipidemias/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Melatonina/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Acetil-CoA Carboxilase/metabolismo , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácido Graxo Sintases/metabolismo , Humanos , Hiperlipidemias/etiologia , Fígado/metabolismo , Masculino , Mesocricetus , Hepatopatia Gordurosa não Alcoólica/etiologia , Triglicerídeos/metabolismo
16.
Biomed Res Int ; 2019: 2835152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984778

RESUMO

Traditionally, in many countries, various parts of the Adansonia digitata (A. digitata) tree have been used in the treatment of many clinical ailments including diarrhea and dysentery. The phytochemical screening has indicated that the leaf extract of A. digitata contains flavonoids, saponins, mucilage, steroids, and alkaloids. Thus, this paper aims to evaluate the hyperglycaemic and hypolipidaemic effects of methanolic extract of A. digitata leaves (200 mg/kg and 400 mg/kg) in diabetic rats. The extract was administered orally for six weeks in the streptozotocin (STZ)-induced diabetic rats. The treatment with the extract caused a significant reduction in the blood glucose, glycosylated hemoglobin, cholesterol, triglycerides, low-density lipoprotein (LDL), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) levels by 46.7%, 46.15%, 48.91%, 43%, 60%, 66%, 45.45%, and 30.4%, respectively, as compared to the diabetic group after the sixth week of treatment. The leaf extract also mitigated the decline of high-density lipoprotein (HDL) level, RBCs count, hemoglobin level, packed cell volume (PCV %), and erythropoietin concentration in diabetic rats by 31%, 33.25%, 24.72%, 51.42%, and 220.68% with respect to the diabetic group. Also, the extract maintained the level of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), and reduced glutathione (GSH) in the diabetic rats. It also reduced the elevation in the white blood corpuscles (WBC) count in the STZ-induced diabetic rats. Our study, therefore, indicates that methanolic extract of A. digitata leaf exerts strong antidiabetic and hypolipidaemic properties in a dose-dependent manner by improving the hematological properties and redox parameters in the experimental diabetic rats.


Assuntos
Adansonia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Glicemia/efeitos dos fármacos , Catalase/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Humanos , Hiperglicemia/sangue , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hipoglicemiantes/administração & dosagem , Interleucina-6/sangue , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
17.
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
18.
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
19.
Am J Chin Med ; 47(2): 323-335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30871361

RESUMO

Red yeast rice (RYR) has been used as an alternative treatment for hyperlipidemia. According to the previous studies, other compounds, besides monacolin K in RYR, may also reduce the serum lipid level. This study aims at examining the efficacy of monacolin K-rich and Gamma-Aminobutyric Acid (GABA)-rich RYR (Monascus pilosus) with regards to treating hyperlipidemia in a randomized control, double-blind clinical trial. In the research, we assigned 50 eligible subjects to monacolin K-rich RYR, GABA-rich RYR and placebo groups ( n=16 , 17, 17, respectively). The concentrations of TC, LDL-C, HDL, TG and blood biochemical data were evaluated at different phases: before applying (visit 1), after 1-month (visit 2), 2-month (visit 3), 3-month (visit 4) of providing the intervention and 1-month after ending the test food (visit 5) among three groups. During the 3-month intervention, the serum TC and LDL-C levels decreased significantly in the monacolin K group compared to the baseline and the other two groups. The Serum TG level declined steadily but was not statistically significant. Meanwhile, no marked differences in the serum HDL level were revealed among the three groups. Most safety assessment data had minor variation except two subjects (in monacolin K and GABA group separately) reported elevated liver enzymes. Monacolin K-rich RYR can reduce cholesterol as expected, while the GABA-rich RYR performed non-significant reduction on serum triglyceride. The research results demonstrate that using different concentrations and ratios between monacolin K and GABA could be beneficial for antihyperlipidemia.


Assuntos
Hiperlipidemias/tratamento farmacológico , Lovastatina/administração & dosagem , Monascus/química , Fitoterapia , Ácido gama-Aminobutírico/administração & dosagem , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hiperlipidemias/sangue , Lovastatina/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Ácido gama-Aminobutírico/química
20.
Phytother Res ; 33(4): 1173-1181, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30859660

RESUMO

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs-CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double-blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL-c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi-square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL-c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs-CRP, and total antioxidant capacity in these patients.


Assuntos
Antioxidantes/uso terapêutico , Proteína C-Reativa/metabolismo , Curcuma/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Adulto , Idoso , Antioxidantes/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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