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1.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361783

RESUMO

Amber-the fossilized resin of trees-is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases.


Assuntos
Adipócitos/efeitos dos fármacos , Âmbar/farmacologia , Misturas Complexas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipolipemiantes/farmacologia , Lipólise/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Âmbar/química , Animais , Diferenciação Celular , Misturas Complexas/química , Etanol/química , Glucose/metabolismo , Glicerol/metabolismo , Hipolipemiantes/química , Leptina/genética , Leptina/metabolismo , Gotículas Lipídicas/química , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Camundongos , Perilipina-1/genética , Perilipina-1/metabolismo , Fosforilação/efeitos dos fármacos , Esterol Esterase/genética , Esterol Esterase/metabolismo , Triglicerídeos/metabolismo
2.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206655

RESUMO

Fish protein consumption exerts beneficial metabolic effects on human health, also correlating with a decreased risk for cardiovascular disease. Fish waste contains high amount of proteins and utilization may offer the opportunity for generating compounds advantageous for human health. Especially, fish waste protein hydrolysates beneficially influence pathways involved in body composition, exerting anti-inflammatory and antioxidant activities, making their potential supplementation in human disorders of increased interest. This study assessed the effect of a 10% (w/w) anchovy waste protein hydrolysate (APH) diet for 12 weeks in reducing atherosclerosis in ApoE-/- mice, through histological and immunohistochemical methods. In addition, monitoring of plaque development was performed, using high-frequency ultrasound and magnetic resonance imaging. Overall, the APH diet attenuated atherosclerotic plaque development, producing a regression of arterial lesions over time (p < 0.05). Twelve weeks on an APH diet had an anti-obesity effect, improving lipid metabolism and reducing hepatic enzyme activity. A significant reduction in plaque size and lipid content was observed in the aortic sinus of APH-fed mice, compared to the control (p < 0.001), whereas no differences in the extracellular matrix and macrophage recruitment were observed. Supplementation of APH significantly attenuates atherosclerosis in ApoE-/- mice, exerting a lipid-lowering activity. The opportunity to use fish waste protein hydrolysates as a nutraceutical in atherosclerosis is worthy of future investigations, representing a low cost, sustainable, and nutritional strategy with minimal environmental impact.


Assuntos
Aterosclerose/terapia , Suplementos Nutricionais , Proteínas de Peixes/farmacologia , Hipolipemiantes/farmacologia , Hidrolisados de Proteína/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Modelos Animais de Doenças , Fezes/química , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica/terapia , Alimentos Marinhos
3.
AAPS PharmSciTech ; 22(5): 203, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244867

RESUMO

Capsanthin, a brightly orange-red-coloured pigment responsible for the peculiar red colour of paprika fruits (Capsicum annuum), belongs to xanthophylls, a class of oxygen-containing carotenoids. The characteristic chemical structure of capsanthin containing a keto group in conjunction with a long chain of 11 conjugated dienes is responsible for its strong radical scavenging and singlet oxygen quenching ability. Chemopreventive, antitumour, skin photo-protective, anti-inflammatory, and antidiabetic activities demonstrated by capsanthin are a consequence of its potent antioxidant action. Anti-obesity, anti-adipogenic, and antihyperlipidaemic activities are some of the more important features of capsanthin. With natural origin, bright red colour, and array of health benefits, capsanthin has a potential to be translated into a commercial cosmeceutical, nutraceutical, and/or pharmaceutical. However, the very low aqueous solubility of capsanthin is responsible for its highly variable and poor oral bioavailability. Moreover, its susceptibility to degradation due to heat, light, oxygen, and moisture poses challenges in the development of stable formulations for this otherwise meritorious compound. The current review presents various pharmacological activities of capsanthin and their underlying mechanisms. The review further discusses hitherto explored formulation strategies to improve solubility and stability of capsanthin. Graphical abstract.


Assuntos
Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Capsicum/química , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Xantofilas/administração & dosagem , Xantofilas/química , Xantofilas/farmacologia , Xantofilas/uso terapêutico
4.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072216

RESUMO

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.


Assuntos
Produtos Biológicos , Fermentação , Alimento Funcional , Soja , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Ingredientes de Alimentos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Estrutura Molecular , Avaliação Nutricional , Osteogênese/efeitos dos fármacos , Probióticos , Soja/química , Soja/metabolismo , Soja/microbiologia
5.
Food Chem ; 358: 129908, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933948

RESUMO

A fucoidan SFP, having novel structure, was extracted from Sargassum fusiforme. It had a molecular weight of 703 kDa and was composed of fucose and galactose with the ratio of 73.16:26.84 (mol%). Structural analyses showed that it mainly consisted of 1,3-, 1,4-, 1,3,4-linked-α-l-Fucp and 1,3-, 1,6-linked-ß-d-Galp, with partial sulfation at C-4, C-3 of fucose units and C-6, C-3 of galactose units. The branches consisted of sulfated fucosyl and galactofucosyl oligosaccharides. The regulatory effects of SFP on the intestinal microbiota in high-fat diet-fed mice were investigated. The high-dosage SFP exhibited good hypolipidemic effects, especially in regulating the high-densitylipoproteincholesterol, non-esterified fatty acid levels and lipase activity. It also significantly decreased the ratio of phyla Firmicutes/Bacteroidetes (P < 0.05). Besides, SFP had certain effects on the richness and diversity of intestinal microbiota. Therefore, SFP exhibited novel structure and certain beneficial effects on the disorder of intestinal microbiota in high-fat diet-fed mice.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Animais , Sequência de Carboidratos , Fucose/química , Galactose/química , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Masculino , Camundongos , Peso Molecular , Sulfatos/química
6.
Prog Lipid Res ; 82: 101099, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33915202

RESUMO

Despite encouraging progresses achieved in the management of viral diseases, efficient strategies to counteract infections are still required. The current global challenge highlighted the need to develop a rapid and cost-effective strategy to counteract the SARS-CoV-2 pandemic. Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection. In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality. Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.


Assuntos
COVID-19/metabolismo , Homeostase , Metabolismo dos Lipídeos , Ácido Mevalônico/metabolismo , COVID-19/tratamento farmacológico , COVID-19/virologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Ácido Mevalônico/antagonistas & inibidores , SARS-CoV-2/isolamento & purificação
7.
Molecules ; 26(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919145

RESUMO

The antihyperglycemic and antilipidemic effects of the tea infusion extracts of leaves from Annona cherimola Miller (IELAc-0.5, IELAc-1.5, and IELAc-3.0) were evaluated on normoglycemic (NG) and streptozocin-induced diabetic (STID) mice. In the acute test, IELAc-1.5 at 300 mg/kg bodyweight (bw) exhibited antihyperglycemic activity on STID mice since the first hour of treatment. Then, its antidiabetic potential was analyzed in a subchronic evaluation. IELAc-1.5 was able to reduce the blood glucose level, glycated hemoglobin (HbA1c), cholesterol (CHO), and triglycerides (TG); high-density lipoprotein (HDL) showed an increase at the end of treatment. IELAc-1.5 did not modify the urine profile at the end of the evaluation, and neither toxicity nor macroscopic organ damage were observed in acute and subchronic assays. In addition, a major flavonol glycoside present in the tea infusion extracts was identified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The analysis of the tea infusion extracts by HPLC revealed that rutin was the major component. This study supports the use of tea infusions from Annona cherimola for the treatment of diabetes and suggests that rutin could be responsible, at least in part, for their antidiabetic properties.


Assuntos
Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Annona/química , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/química , Hipolipemiantes/química , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Chá
8.
Nutrients ; 13(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922621

RESUMO

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg-1∙d-1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg-1∙d-1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.


Assuntos
Fármacos Antiobesidade/farmacologia , Araliaceae/química , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Colesterol/sangue , Colesterol/urina , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Malondialdeído/urina , Camundongos Endogâmicos C57BL , Óxido Nítrico/sangue , Óxido Nítrico/urina , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/toxicidade , Proteínas/genética , Proteínas/metabolismo , Água/química
9.
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
10.
Int J Mol Sci ; 22(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916086

RESUMO

Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, p < 0.05), visceral adipose tissue mass (-46%, p < 0.05), and visceral adipocyte size (-20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, p < 0.05) and infiltration of macrophages (-72%, p < 0.05), while concomitantly upregulating the expression of fatty acid ß-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice.


Assuntos
Dislipidemias/prevenção & controle , Fígado Gorduroso/prevenção & controle , Fenofibrato/uso terapêutico , Hipolipemiantes/uso terapêutico , Obesidade Abdominal/prevenção & controle , Adipócitos/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Avaliação Pré-Clínica de Medicamentos , Feminino , Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , Gordura Intra-Abdominal/metabolismo , Camundongos Endogâmicos C57BL , Ovariectomia , PPAR gama/metabolismo
11.
Molecules ; 26(7)2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33916540

RESUMO

Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.


Assuntos
Albuminúria/tratamento farmacológico , Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Hibiscus/química , Hipolipemiantes/farmacologia , Rim/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Albuminúria/sangue , Albuminúria/patologia , Animais , Fármacos Antiobesidade/isolamento & purificação , Antioxidantes/isolamento & purificação , Ácido Ascórbico/sangue , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Transferase/sangue , Hipolipemiantes/isolamento & purificação , Insulina/sangue , Rim/metabolismo , Rim/fisiopatologia , Leptina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Extratos Vegetais/química , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Triglicerídeos/sangue
12.
Biomed Pharmacother ; 137: 111372, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761598

RESUMO

Menopausal women are susceptible to have high risk of cardiovascular diseases, type II diabetes and osteoporosis due to the metabolic disorder caused by estrogen deficiency. Accumulating evidence supports that gut microbiota is a key regulator of metabolic diseases. Our previous metabolomics study interestingly demonstrated that the anti-osteoporotic effects of lignan-rich fraction (SWCA) from Sambucus wialliamsii Hance were related to the restoration of a series of lipid and glucose metabolites. This study aims to investigate how SWCA modulates lipid and glucose metabolism and the underlying mechanism. Our results show that oral administration of SWCA (140 mg/kg and 280 mg/kg) for 10 weeks alleviated dyslipidemia, improved liver functions, prevented glucose tolerance and insulin actions, attenuated system inflammation and improved intestinal barrier in OVX rats. It also induced a high abundance of Actinobacteria, and restored microbial composition. We are the first to report the protective effects of the lignan-rich fraction from S. williamsii on dyslipidemia and insulin resistance. Our findings provide strong evidence for the application of this lignan-rich fraction to treat menopausal lipid disorder and insulin resistance-related diseases.


Assuntos
Dislipidemias/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipolipemiantes/farmacologia , Resistência à Insulina , Lignanas/farmacologia , Sambucus/química , Administração Oral , Animais , Citocinas/metabolismo , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Fígado/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/farmacologia , Caules de Planta/química , Ratos , Ratos Sprague-Dawley
13.
Expert Rev Clin Pharmacol ; 14(5): 545-551, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33691561

RESUMO

INTRODUCTION: Dyslipidemia is a common condition that increases the risk of heart diseases and stroke. High levels of low-density lipoprotein-cholesterol (LDL-C) are correlated with a higher risk for heart disease. A drug class known as 'statins' is the gold standard for LDL-C-lowering, but its use in some patients is limited by its adverse effects of myalgias and myopathies. Use of other LDL-C-lowering agents is frequently limited by cost and degree of efficacy. Additionally, many high-risk atherosclerotic cardiovascular disease patients fail to meet LDL-C goals despite maximally tolerated statin therapy with or without the addition of a non-statin agent. AREAS COVERED: This review covers the pharmacology, pharmacokinetics, clinical trials, and clinical implications of bempedoic acid. A PubMed search was conducted using the terms bempedoic, bempedoic acid, Nexletol, ETC-1002, and adenosine triphosphate citrate lyase inhibitor. Additional data were obtained from the prescribing information and relevant guidelines. All clinical trials were included. EXPERT OPINION: Bempedoic acid has not been shown to cause myalgias or myopathies and is likely to be competitively affordable compared to other LDL-C-lowering agents. Bempedoic acid has been shown to be superior compared to placebo and provides additional LDL-C lowering on top of maximally tolerated statin therapy or combined with ezetimibe alone.


Assuntos
Ácidos Dicarboxílicos/administração & dosagem , Dislipidemias/tratamento farmacológico , Ácidos Graxos/administração & dosagem , Hipolipemiantes/administração & dosagem , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Dicarboxílicos/farmacologia , Quimioterapia Combinada , Dislipidemias/complicações , Dislipidemias/fisiopatologia , Ácidos Graxos/efeitos adversos , Ácidos Graxos/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacologia
14.
Int Immunopharmacol ; 95: 107340, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33667999

RESUMO

Obesity is an important factor implicated in chronic kidney disease (CKD). Juglanin (Jug) is a natural compound extracted from the crude Polygonumaviculare, showing anti-inflammatory and anti-diabetic effects. However, whether Jug has protective effects against obesity-induced renal injury, little has been investigated. Herein, we attempted to explore the potential of Jug in mediating obesity-induced kidney disease in high fat diet (HFD)-challenged mice. Our results suggested that chronic HFD feeding markedly increased the body weights of mice compared to the ones fed with normal chow diet (NCD), along with significant glucose intolerance and insulin resistance. However, these metabolic disorders induced by HFD were effectively alleviated by Jug treatments in a dose-dependent manner. Moreover, HFD-challenged mice showed apparent histopathological changes in renal tissues with significant collagen accumulation, which were attenuated by Jug supplementation. In addition, Jug treatment decreased the expression levels of kidney injury molecule-1 (KIM-1), while increased nephrin and podocin expression levels in kidney of HFD-challenged mice, improving the renal dysfunction. Furthermore, HFD led to lipid deposition in kidney samples of mice by enhancing abnormal lipid metabolism. In addition, HFD promoted the releases of circulating pro-inflammatory cytokines, and enhanced the renal inflammation by activating nuclear factor-kappa B/histone deacetylase 3 (NF-κB/HDAC3) signaling. HFD-induced dyslipidemia and inflammation were considerably abrogated by Jug administration in mice. The protective effects of Jug against renal injury were confirmed in palmitate (PA)-stimulated HK2 cells in vitro mainly through suppressing the nuclear translocation of NF-κB and HDAC3, repressing inflammation and lipid accumulation eventually. Hence, Jug could ameliorate HFD-induced kidney injury mainly through blocking the NF-κB/HDAC3 nuclear translocation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dislipidemias/tratamento farmacológico , Glicosídeos/uso terapêutico , Hipolipemiantes/uso terapêutico , Quempferóis/uso terapêutico , Nefropatias/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dieta Hiperlipídica , Dislipidemias/metabolismo , Dislipidemias/patologia , Glicosídeos/farmacologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Hipolipemiantes/farmacologia , Resistência à Insulina , Quempferóis/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Food Chem ; 351: 129340, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33662904

RESUMO

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


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Amido Resistente/farmacologia , Zingiberales/química , Animais , Hidrólise , Camundongos
16.
Biosci Biotechnol Biochem ; 85(6): 1395-1404, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33784390

RESUMO

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods.


Assuntos
Bile/metabolismo , Hipolipemiantes/farmacologia , Lactobacillus/efeitos dos fármacos , Lactobacillus/metabolismo , Liraglutida/farmacologia , Animais , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Masculino , Camundongos
17.
J Ethnopharmacol ; 272: 113926, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33596472

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect. AIM OF THE STUDY: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula. MATERIALS AND METHODS: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MSn) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MSn) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC50) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN. RESULTS: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside. CONCLUSIONS: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Células Hep G2 , Humanos , Hiperlipidemias/sangue , Hipolipemiantes/administração & dosagem , Hipolipemiantes/análise , Lipídeos/sangue , Ácido Oleico/toxicidade , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Equivalência Terapêutica
18.
Biochim Biophys Acta Mol Basis Dis ; 1867(6): 166100, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33549744

RESUMO

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common inborn long-chain fatty acid oxidation (FAO) disorder. VLCAD deficiency is characterized by distinct phenotypes. The severe phenotypes are potentially life-threatening and affect the heart or liver, with a comparatively milder phenotype characterized by myopathic symptoms. There is an unmet clinical need for effective treatment options for the myopathic phenotype. The molecular mechanisms driving the gradual decrease in mitochondrial function and associated alterations of muscle fibers are unclear. The peroxisome proliferator-activated receptor (PPAR) pan-agonist bezafibrate is a potent modulator of FAO and multiple other mitochondrial functions and has been proposed as a potential medication for myopathic cases of long-chain FAO disorders. In vitro experiments have demonstrated the ability of bezafibrate to increase VLCAD expression and activity. However, the outcome of small-scale clinical trials has been controversial. We found VLCAD deficient patient fibroblasts to have an increased oxidative stress burden and deranged mitochondrial bioenergetic capacity, compared to controls. Applying heat stress under fasting conditions to bezafibrate pretreated patient cells, caused a marked further increase of mitochondrial superoxide levels. Patient cells failed to maintain levels of the essential thiol peptide antioxidant glutathione and experienced a decrease in cellular viability. Our findings indicate that chronic PPAR activation is a plausible initiator of long-term pathogenesis in VLCAD deficiency. Our findings further implicate disruption of redox homeostasis as a key pathogenic mechanism in VLCAD deficiency and support the notion that a deranged thiol metabolism might be an important pathogenic factor in VLCAD deficiency.


Assuntos
Bezafibrato/farmacologia , Síndrome Congênita de Insuficiência da Medula Óssea/tratamento farmacológico , Metabolismo Energético , Fibroblastos/efeitos dos fármacos , Hipolipemiantes/farmacologia , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Doenças Musculares/tratamento farmacológico , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Síndrome Congênita de Insuficiência da Medula Óssea/metabolismo , Síndrome Congênita de Insuficiência da Medula Óssea/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Erros Inatos do Metabolismo Lipídico/metabolismo , Erros Inatos do Metabolismo Lipídico/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Doenças Musculares/metabolismo , Doenças Musculares/patologia , Estresse Oxidativo , Receptores Ativados por Proliferador de Peroxissomo/genética
19.
Environ Sci Pollut Res Int ; 28(21): 27207-27217, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33507508

RESUMO

This study aimed to examine the impact of ethanolic Avicennia marina (A. marina) leaves extract against seven pathogenic bacteria and the protective effect of this plant against hyperlipidemia caused by dexamethasone (DEX)-treated rats. Forty-eight male rats weighing between 150 and 200 g were randomly selected into six groups containing eight rats in each group. Moreover, in vitro antioxidant DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging activity, FRAP (ferric reducing antioxidant power), and ABTS assay were also analyzed for leaf extract. Results showed that the IC50 values were observed as 193.9 ± 1.03 µg/mL, 340.29 ± 8.16 µM TE/mg, and 326.8 ± 6.14 µM TE/mg for DPPH, FRAP, and ABTS radical scavenging activities, respectively. A. marina leaves ethanolic extract exhibited higher activity against Candida albicans and Bacillus subtilis, moderate activity against Salmonella typhimurium, and Vibrio damsel. The administration of DEX resulted in significant (P < 0.05) increase in the levels of MDA concentration, TG, TC, LDL, LDH, and glucose but decreased significantly in HDL. Treatment with A. marina extract positively reversed the distorted lipid profile and peroxidation and improved MDA, GSH, NO, and SOD activities in DEX-administered rats. Histological investigation of liver tissue sections showed that the treatment with A. marina leaves extract moderate the fatty change caused by DEX. It is concluded that A. marina leaves extract improved the hypolipidemic property of DEX administration in comparison with standard treatment with atorvastatin.


Assuntos
Antioxidantes , Avicennia , Animais , Antibacterianos/farmacologia , Hipolipemiantes/farmacologia , Masculino , Extratos Vegetais , Folhas de Planta , Ratos
20.
Mar Drugs ; 19(1)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435383

RESUMO

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran's Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger's linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.


Assuntos
Anticolesterolemiantes/farmacologia , Quitosana/farmacologia , Suplementos Nutricionais , Animais , Hipolipemiantes/farmacologia , Camundongos , Ratos
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