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1.
Biomed Pharmacother ; 139: 111494, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243595

RESUMO

This study set out to optimize simvastatin (SV) in lipid nanoparticles (SLNs) to improve bioavailability, efficacy and alleviate adverse effects. Simvastatin-loaded solid lipid nanoparticles (SV-SLNs) were prepared by hot-melt ultrasonication method and optimized by box-Behnken experimental design. Sixty Wister albino rats were randomly assigned into six groups and treated daily for 16 weeks: control group, the group fed with 20 g of high-fat diet (HFD), group treated with vehicle (20 mg/kg, P.O.) for last four weeks, group treated with HFD and SV (20 mg/kg, P.O.) / or SV-SLNs (20 mg/kg/day, P.O.) / or SV-SLNs (5 mg/kg, P.O.) at last four weeks. Blood, liver tissues, and quadriceps muscles were collected for biochemical analysis, histological and immunohistochemical assays. The optimized SV-SLNS showed a particle-size 255.2 ± 7.7 nm, PDI 0.31 ± 0.09, Zeta-potential - 19.30 ± 3.25, and EE% 89.81 ± 2.1%. HFD showed severe changes in body weight liver functions, lipid profiles, atherogenic index (AIX), albumin, glucose, insulin level, alkaline phosphatase as well as muscle injury, oxidative stress biomarkers, and protein expression of caspase-3. Simvastatin treatment in animals feed with HFD showed a significant improvement of all tested parameters, but it was associated with hepatotoxicity, myopathy, and histological changes in quadriceps muscles. SV-SLNs exhibited a significant improvement of all biochemical, histological examinations, and immunohistochemical assays. SV-SLNs (5 mg/kg) treatment returns all measured parameters to control itself. These results represent that SV-SLNs is a promising candidate as a drug carrier for delivering SV with maximum efficacy and limited adverse reaction.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Lipídeos/química , Doenças Musculares/tratamento farmacológico , Nanopartículas/química , Sinvastatina/farmacologia , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Masculino , Tamanho da Partícula , Ratos , Ratos Wistar
2.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210097

RESUMO

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG-Untreated group; CTRL-control; FDW-olive oil + 20% fructose; FDW-PS-PS (125 mg/kg) + 20% fructose; FDW-NGN-naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia.


Assuntos
Frutose/efeitos adversos , Hiperlipidemias , Síndrome Metabólica , Metanol/química , Obesidade , Piper/química , Extratos Vegetais , Animais , Frutose/farmacologia , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
4.
J Vet Intern Med ; 35(4): 1733-1742, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096101

RESUMO

BACKGROUND: Safe, effective, and readily available drug therapies are required for the management of hyperlipidemia and its associated complications in dogs. OBJECTIVES: To investigate the efficacy of a micronized, nanocrystal formulation of fenofibrate (Tricor) in the treatment of hyperlipidemia in dogs. ANIMALS: Ten client-owned dogs with primary (n = 7) and secondary (n = 3) hyperlipidemia. All dogs had hypertriglyceridemia at baseline; 3 dogs also had hypercholesterolemia. METHODS: Prospective dose-escalation study. Dogs were treated with fenofibrate orally once daily in up to 3 cycles of 21 days each. Fenofibrate dose was increased at the end of each cycle if hypertriglyceridemia persisted and adverse effects were not documented. Complete blood count, biochemistry, and urine protein:creatinine ratio were collected serially. Baseline (T0) parameters were compared to time of maximal reduction in serum triglyceride concentrations (T1) and reported as median (range). RESULTS: Triglycerides normalized in all dogs (T0 = 662 mg/dL [189-2391]; T1 = 113 mg/dL [81-132]; P = .002). Fenofibrate dose at T1 = 6.4 mg/kg PO q24h (range, 2.2-13.5). T1 was achieved at 3 (n = 4), 6 (n = 4), and 9 (n = 2) weeks. Serum cholesterol concentrations decreased in 9 of 10 dogs. Quiet demeanor and firm stools in 1 dog were the only reported adverse reactions. Fenofibrate administration resulted in a significant reduction in median alkaline phosphatase activity (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE: Over 21 to 63 days, TriCor was effective in the management of primary and secondary hyperlipidemia in dogs.


Assuntos
Doenças do Cão , Fenofibrato , Hiperlipidemias , Nanopartículas , Animais , Doenças do Cão/tratamento farmacológico , Cães , Fenofibrato/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/veterinária , Hipolipemiantes/uso terapêutico , Estudos Prospectivos
5.
Sr Care Pharm ; 36(6): 284-303, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34016226

RESUMO

OBJECTIVE: To provide an up-to-date review of current hyperlipidemia guidelines and discuss pharmacotherapeutic management of hyperlipidemia in older individuals. DATA SOURCES: A PubMed search of articles published through October 2020 was performed using a combination of the following words: older adults, hyperlipidemia, statin, ezetimibe, fibrate, fish oil, niacin, bile acid sequestrant, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. STUDY SELECTION/DATA EXTRACTION: Relevant original research, review articles, and guidelines were assessed for the management of hyperlipidemia in the older individuals. References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results. DATA SYNTHESIS: Hyperlipidemia is a common chronic disease state in the elderly population, though there is limited evidence for clinical outcomes in older people when compared withwith the general adult population. Statins have the most evidence for primary and secondary prevention of cardiovascular disease in older people, though ezetimibe and PCSK9 inhibitors have a role as add-on or monotherapy in patients who do not tolerate statins. CONCLUSION: Optimal management of hyperlipidemia in older people is important in order to avoid further complications and improve outcomes. Pharmacists can help improve management in the elderly by incorporating up-to-date evidence from guidelines and providing medication education specifically for this population.


Assuntos
Anticolesterolemiantes , Hiperlipidemias , Idoso , LDL-Colesterol , Humanos , Hiperlipidemias/tratamento farmacológico , Pró-Proteína Convertase 9
6.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1795-1802, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982484

RESUMO

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.


Assuntos
Hiperlipidemias , Animais , Transporte Biológico , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
7.
Monaldi Arch Chest Dis ; 91(2)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942600

RESUMO

To the Editor COVID-19 (COrona VIrus Disease) patients with cardiovascular (CV) disease, multiple CV risk factors or comorbidities (i.e., arterial hypertension and diabetes) were shown to be more prone to a worse prognosis. SARS-CoV-2 is a still unknown enemy and the role of concomitant cardiovascular therapies has been controversial in the early stages, particularly with regard to Angiotensin-Converting Enzyme inhibitors...


Assuntos
COVID-19/imunologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , COVID-19/complicações , COVID-19/mortalidade , COVID-19/fisiopatologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Desprescrições , Humanos , Hiperlipidemias/complicações , Prevenção Primária , SARS-CoV-2 , Prevenção Secundária
8.
Life Sci ; 278: 119579, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33961852

RESUMO

Hyperlipidemia, an independent risk factor for atherosclerosis, is regarded as a lipid metabolism disorder associated with elevated plasma triglyceride and/or cholesterol. Genetic factors and unhealthy lifestyles, such as excess caloric intake and physical inactivity, can result in hyperlipidemia. Taurine, a sulfur-containing non-essential amino acid, is abundant in marine foods and has been associated with wide-ranging beneficial physiological effects, with special reference to regulating aberrant lipid metabolism. Its anti-hyperlipidemic mechanism is complex, which is related to many enzymes in the process of fat anabolism and catabolism (e.g., HMGCR, CYP7A1, LDLR, FXR, FAS and ACC). Anti-inflammatory and antioxidant molecular targets, lipid autophagy, metabolic reprogramming and gut microbiota will also be reviewed.


Assuntos
Hiperlipidemias/tratamento farmacológico , Taurina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Autofagia , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal , Humanos , Inflamação , Metabolismo dos Lipídeos , Lipídeos/sangue , Fígado/metabolismo , Ratos , Taurina/química , Triglicerídeos/metabolismo
9.
Food Funct ; 12(8): 3572-3585, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900346

RESUMO

Type 2 diabetic mellitus (T2DM) is a complicated metabolic disorder that is now considered as a major global public health problem. Fucoidan exhibits diverse biological activities, especially prevention of metabolic diseases. In this regard, we herein aimed to reveal the beneficial effect of Sargassum fusiforme fucoidan (SFF) on high-fat diet (HFD) and streptozotocin (STZ) induced T2DM mice. We noted that on the one hand, SFF significantly decreased fasting blood glucose, diet and water intake, and hyperlipidemia, while on the other hand, it improved glucose tolerance. Furthermore, SFF reduced epididymal fat deposition, attenuated the pathological changes in heart and liver tissues, and decreased oxidative stress in diabetic mice. To explore the underlying mechanisms of these ameliorative effects, the gut microbiota was analyzed. Notably, SFF highly enriched benign microbes including Bacteroides, Faecalibacterium and Blautia, as well as increased levels of (R)-carnitine and choline in the colon of diabetic mice. This may be a potential mechanism for alleviating T2DM, thus implying the benefits of SFF as an adjuvant agent for T2DM treatment. Taken together, this study demonstrated a promising application of fucoidan as one of the adjuvant agents for the management of T2DM in the future.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Sargassum/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/farmacologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia
10.
Nutrients ; 13(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922242

RESUMO

As a natural active substance that can effectively improve blood lipid balance in the body, hypolipidemic active peptides have attracted the attention of scholars. In this study, the effect of walnut meal peptides (WMP) on lipid metabolism was investigated in rats fed a high-fat diet (HFD). The experimental results show that feeding walnut meal peptides counteracted the high-fat diet-induced increase in body, liver and epididymal fat weight, and reduce the serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol and hepatic cholesterol and triglyceride content. Walnut meal peptides also resulted in increased HDL-cholesterol while reducing the atherosclerosis index (AI). Additionally, the stained pathological sections of the liver showed that the walnut meal peptides reduced hepatic steatosis and damage caused by HFD. Furthermore, walnut meal peptide supplementation was associated with normalization of elevated apolipoprotein (Apo)-B and reduced Apo-A1 induced by the high-fat diet and with favorable changes in the expression of genes related to lipid metabolism (LCAT, CYP7A1, HMGR, FAS). The results indicate that walnut meal peptides can effectively prevent the harmful effects of a high-fat diet on body weight, lipid metabolism and liver fat content in rats, and provide, and provide a reference for the further development of walnut meal functional foods.


Assuntos
Dieta Hiperlipídica , Hiperlipidemias/tratamento farmacológico , Juglans/química , Metabolismo dos Lipídeos , Fígado/metabolismo , Peptídeos/uso terapêutico , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Aminoácidos/análise , Animais , Apolipoproteínas/metabolismo , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/patologia , Colesterol/metabolismo , Ingestão de Energia/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrólise , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Peptídeos/farmacologia , Ratos Sprague-Dawley
11.
Int J Mol Sci ; 22(8)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33921777

RESUMO

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κß), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.


Assuntos
GMP Cíclico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Nucleotídeos Cíclicos/metabolismo , Obesidade/complicações , Própole/uso terapêutico , Animais , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Orlistate/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
12.
Molecules ; 26(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803259

RESUMO

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.


Assuntos
Ezetimiba/farmacologia , Hiperlipidemias/tratamento farmacológico , Nanotecnologia/métodos , Animais , Disponibilidade Biológica , Dieta Hiperlipídica/efeitos adversos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ezetimiba/administração & dosagem , Hiperlipidemias/metabolismo , Lipídeos/química , Lipídeos/farmacologia , Masculino , Nanopartículas/química , Nanoestruturas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Triglicerídeos , Difração de Raios X
13.
Clin Chim Acta ; 518: 134-141, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33823149

RESUMO

Hyperlipidemia is correlated with several health problems that contain the combination of hypertension, obesity, and diabetes mellitus, which are grouped as metabolic syndrome. Though the lipid-lowering agents, such as statins, which aims to reduce serum low-density lipoprotein cholesterol (LDL-C) has been considered as one of the most effective therapeutics in treating hyperlipidemia and coronary artery diseases, the persistent high risk of atherosclerosis after intensive lipid-lowering therapy could not be simply explained by hyperlipidemia. Therefore, it is necessary to identify novel factors to manage treatment and to predict risk of cardio-metabolic events. Endeavor over the past several decades has demonstrated the important functions of microRNAs in modulating macrophage activation, lipid metabolism, and hyperlipidemia. In the present review, we summarized the recent findings which highlighted the contributions of microRNAs in regulating serum lipid metabolism. Furthermore, we also provided the potential mechanisms whereby microRNAs controlled lipid metabolism and the risk of cardio-metabolic disorders, which could help us to identify microRNAs as a promising therapeutic target for hyperlipidemia and its related cardiovascular diseases.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , MicroRNAs , LDL-Colesterol , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Hipolipemiantes/uso terapêutico , MicroRNAs/genética , Fatores de Risco
14.
Aging (Albany NY) ; 13(8): 11470-11490, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864447

RESUMO

BACKGROUNDS: A major side effect of statin, a widely used drug to treat hyperlipidemia, is skeletal myopathy through cell apoptosis. The aim of this study is to investigate the roles of microRNA in statin-induced injury. METHODS: Apolipoprotein E knockout (ApoE-/-) mice were administered with simvastatin (20 mg/kg/day) for 8 weeks. Exercise capacity was evaluated by hanging grid test, forelimb grip strength, and running tolerance test. RESULTS: In cultured skeletal muscle cells, statin increased the levels of miR-1a but decreased the levels of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in a time or dose dependent manner. Both computational target-scan analysis and luciferase gene reporter assay indicated that MAP3K1 is the target gene of miR-1a. Statin induced cell apoptosis of skeletal muscle cells, but abolished by downregulating of miR-1a or upregulation of MAP3K1. Further, the effects of miR-1a inhibition on statin-induced cell apoptosis were ablated by MAP3K1 siRNA. In ApoE-/- mice, statin induced cell apoptosis of skeletal muscle cells and decreased exercise capacity in mice infected with vector, but not in mice with lentivirus-mediated miR-1a gene silence. CONCLUSION: Statin causes skeletal injury through induction of miR-1a excessive expression to decrease MAP3K1 gene expression.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , MAP Quinase Quinase Quinase 1/genética , MicroRNAs/metabolismo , Fibras Musculares Esqueléticas/patologia , Doenças Musculares/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hiperlipidemias/tratamento farmacológico , Camundongos , Camundongos Knockout para ApoE , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Fibras Musculares Esqueléticas/efeitos dos fármacos , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/patologia , Condicionamento Físico Animal , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Sinvastatina/efeitos adversos , Regulação para Cima/efeitos dos fármacos
16.
Zhongguo Zhong Yao Za Zhi ; 46(1): 190-195, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645070

RESUMO

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.


Assuntos
Hiperlipidemias , Animais , Etanol , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Fígado , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Triglicerídeos
17.
Dokl Biochem Biophys ; 496(1): 10-13, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689066

RESUMO

It was established that the administration of an aqueous solution of bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium to animals daily for 2 months at a dose of the active substance of 10 mg/kg of the animal's weight leads to inhibition of the total activity of the alkaline phospholipase A2 of mononuclear cells. The results of the study can be used to correct lipid metabolism in the development of disorders in hyperlipidemia. This makes it possible to expand the scope of use of the studied substance and create new pharmaceuticals based on bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium prevent and inhibit the development of hyperlipidemia.


Assuntos
Etanolaminas/farmacologia , Hiperlipidemias/tratamento farmacológico , Compostos Organometálicos/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Fosfolipases A2/metabolismo , Animais , Colesterol/sangue , Germânio/química , Germânio/farmacologia , Hiperlipidemias/enzimologia , Hiperlipidemias/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/enzimologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fosfolipases A2/sangue , Coelhos
18.
Med Clin North Am ; 105(2): 263-272, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33589101

RESUMO

Although statins are generally safe and well tolerated, some patients experience muscle complaints that can be attributed to their use. Those with muscle discomfort but no demonstrable muscle weakness or creatine kinase (CK) elevations may have statin-associated muscle symptoms. Individuals with elevated CK levels, with or without muscle discomfort or weakness, may have statin-associated myotoxicity. Rare patients have statin-associated autoimmune myopathy, a disease characterized by proximal muscle weakness, elevated CK levels, and autoantibodies recognizing hydroxy-methyl-glutaryl coenzyme A reductase. In this review, the author provides the clinician with a practical approach to diagnosing and managing patients with each of these statin side effects.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias/tratamento farmacológico , Miotoxicidade , Autoimunidade/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/sangue , Lipoproteínas LDL/análise , Miotoxicidade/etiologia , Miotoxicidade/imunologia , Miotoxicidade/fisiopatologia , Miotoxicidade/terapia
19.
Medicine (Baltimore) ; 100(6): e24345, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578530

RESUMO

BACKGROUND: Hypertension combined with hyperlipidemia (HTN-HLP), as a common clinical chronic disease combination, will increase the incidence of cardiovascular and cerebrovascular diseases, increase the occurrence of sudden death and other adverse events. At present, the commonly used therapeutic drugs are mainly combined with antihypertensive drugs and lipid-lowering drugs, which not only have poor compliance, but also have adverse reactions. Currently, traditional Chinese medicine, as a traditional medicine in China, has been applied in clinical practice for thousands of years and has rich clinical experience in treating HTN-HLP. However, there is no systematic evaluation of the efficacy, safety and improvement of patients' quality of life. This systematic review and meta-analysis will assess studies of the effects and safety of Chinese herbal medicine (CHM) for HTN-HLP patients. METHODS: We will search PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science (ISI), China National Knowledge Infrastructure, Wan fang Database, Chinese Scientific Journals Full-Text Database (VIP) and China Biological Medicine Database from the time when databases were established to 01, February 2021. After a series of screening, randomized controlled trials (RCTs) will be included related to CHM for HTN-HLP. Two researchers will assess the RCTs through the Cochrane bias risk assessment tool. And the evidence grade of the results will be evaluated by GRADEprofiler software. RESULTS: This study will provide a reliable evidence for the efficiency of antihypertensive and reducing blood lipids of CHM for HTN-HLP. CONCLUSION: We will summarize the methods and provide sufficient evidence to confirm the efficacy and safety of CHM for HTN-HLP. INPLASY REGISTRATION NUMBER: INPLASY2020110144.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Hipolipemiantes/uso terapêutico
20.
Arterioscler Thromb Vasc Biol ; 41(4): e208-e223, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33535788
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