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1.
J Ethnopharmacol ; 322: 117557, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38072291

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. AIMS: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. RESULTS: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks' experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. CONCLUSION: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.


Assuntos
Aterosclerose , Fabaceae , Galactanos , Hipercolesterolemia , Hiperlipidemias , Mananas , Gomas Vegetais , Camundongos , Animais , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , LDL-Colesterol , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Metabolismo dos Lipídeos , Hiperlipidemias/tratamento farmacológico , Triglicerídeos/metabolismo , Fígado , Lipoproteínas , Aterosclerose/tratamento farmacológico , Peso Corporal , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/metabolismo
2.
Nutrients ; 15(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38140315

RESUMO

Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide, and hypercholesterolemia is a central risk factor for atherosclerosis. This study evaluated the effects of Totum-070, a plant-based polyphenol-rich supplement, in hamsters with high-fat diet (HFD)-induced dyslipidemia. The molecular mechanisms of action were explored using human Caco2 enterocytes. Totum-070 supplementation reduced the total cholesterol (-41%), non-HDL cholesterol (-47%), and triglycerides (-46%) in a dose-dependent manner, compared with HFD. HFD-induced hepatic steatosis was also significantly decreased by Totum-070, an effect associated with the reduction in various lipid and inflammatory gene expression. Upon challenging with olive oil gavage, the post-prandial triglyceride levels were strongly reduced. The sterol excretion in the feces was increased in the HFD-Totum-070 groups compared with the HFD group and associated with reduction of intestinal cholesterol absorption. These effects were confirmed in the Caco2 cells, where incubation with Totum-070 inhibited cholesterol uptake and apolipoprotein B secretion. Furthermore, a microbiota composition analysis revealed a strong effect of Totum-070 on the alpha and beta diversity of bacterial species and a significant decrease in the Firmicutes to Bacteroidetes ratio. Altogether, our findings indicate that Totum-070 lowers hypercholesterolemia by reducing intestinal cholesterol absorption, suggesting that its use as dietary supplement may be explored as a new preventive strategy for cardiovascular diseases.


Assuntos
Aterosclerose , Hipercolesterolemia , Hiperlipidemias , Cricetinae , Animais , Humanos , Hipercolesterolemia/etiologia , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Dieta Hiperlipídica/efeitos adversos , Polifenóis/farmacologia , Polifenóis/metabolismo , Células CACO-2 , Mesocricetus , Colesterol/metabolismo , Hiperlipidemias/metabolismo , Triglicerídeos/metabolismo , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Fígado/metabolismo
3.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281217

RESUMO

BACKGROUND AND AIMS: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular diseases. Although resistant to hypercholesterolemia, the mouse is a prominent model in cardiovascular research. To assess the contribution of bile acids to this protective phenotype, we explored the impact of a 2-week-long dietary cholesterol overload on cholesterol and bile acid metabolism in mice. METHODS: Bile acid, oxysterol, and cholesterol metabolism and transport were assessed by quantitative real-time PCR, western blotting, GC-MS/MS, or enzymatic assays in the liver, the gut, the kidney, as well as in the feces, the blood, and the urine. RESULTS: Plasma triglycerides and cholesterol levels were unchanged in mice fed a cholesterol-rich diet that contained 100-fold more cholesterol than the standard diet. In the liver, oxysterol-mediated LXR activation stimulated the synthesis of bile acids and in particular increased the levels of hydrophilic muricholic acids, which in turn reduced FXR signaling, as assessed in vivo with Fxr reporter mice. Consequently, biliary and basolateral excretions of bile acids and cholesterol were increased, whereas portal uptake was reduced. Furthermore, we observed a reduction in intestinal and renal bile acid absorption. CONCLUSIONS: These coordinated events are mediated by increased muricholic acid levels which inhibit FXR signaling in favor of LXR and SREBP2 signaling to promote efficient fecal and urinary elimination of cholesterol and neo-synthesized bile acids. Therefore, our data suggest that enhancement of the hydrophilic bile acid pool following a cholesterol overload may contribute to the resistance to hypercholesterolemia in mice. This work paves the way for new therapeutic opportunities using hydrophilic bile acid supplementation to mitigate hypercholesterolemia.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol na Dieta/efeitos adversos , Ácidos Cólicos/uso terapêutico , Hipercolesterolemia/prevenção & controle , Animais , Colesterol na Dieta/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hipercolesterolemia/etiologia , Masculino , Camundongos Endogâmicos C57BL , Receptores Citoplasmáticos e Nucleares/metabolismo
4.
J Oleo Sci ; 70(7): 965-977, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121030

RESUMO

Due to the growing demand of n-3 polyunsaturated fatty acids (PUFA) as supplements and pharmaceutical products worldwide, there are concerns about the exhaustion of n-3 PUFA supply sources. We have successfully prepared high-quality scallop oil (SCO), containing high eicosapentaenoic acid and phospholipids contents, from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), which is the largest unutilized marine resource in Japan. This study compared the cholesterol-lowering effect of SCO with fish oil (menhaden oil, MO) and krill oil (KO) in obese type II diabetic KK-A y mice. Four-week-old male KK-A y mice were divided into four groups; the control group was fed the AIN93G-modified high-fat (3 wt% soybean oil + 17 wt% lard) diet, and the other three groups (SCO, MO, and KO groups) were fed a high-fat diet, in which 7 wt% of the lard in the control diet was replaced with SCO, MO, or KO, respectively. After the mice were fed the experimental diet for 42 days, their serum, liver, and fecal lipid contents as well as their liver mRNA expression levels were evaluated. The SCO group had significantly decreased cholesterol levels in the serum and liver; this decrease was not observed in the MO and KO groups. The cholesterol-lowering effect of SCO was partly mediated by the enhancement of fecal total sterol excretion and expression of liver cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis. These results indicate that dietary SCO exhibits serum and liver cholesterol-lowering effects that are not found in dietary MO and KO and can help prevent lifestyle-related diseases.


Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Óleos de Peixe/uso terapêutico , Hipercolesterolemia/dietoterapia , Pectinidae/química , Animais , Colesterol/sangue , Colesterol 7-alfa-Hidroxilase/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Euphausiacea/química , Ácidos Graxos/análise , Ácidos Graxos/química , Fezes/química , Peixes , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/química , Masculino , Camundongos , RNA Mensageiro/metabolismo , Triglicerídeos/sangue , Triglicerídeos/química
5.
Nutrients ; 13(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572980

RESUMO

Coronary heart disease (CHD) is one of the leading causes of mortality in many low-income and middle-income countries, including Indonesia, with elevated blood cholesterol level being one of significant risk factors for this condition. The problem should be addressed by combining healthy lifestyle and diet, where functional foods having a cholesterol-lowering activity could play a significant role. A group of compounds that had been proven to show cholesterol-lowering ability are plant sterols. To develop more suitable functional foods that could substantially contribute to hypercholesterolemia prevention in Indonesian population, up-to-date data about plant sterols dietary intake are required, and were not available until this research was done. This study aimed to estimate daily plant sterols intake and to determine the consumption pattern of foods containing plant sterols in rural and urban area of Bogor, West Java, Indonesia. The research was conducted with a cross-sectional design, with 200 respondents. The study revealed that the level of plant sterols intake in Bogor reached on average 229.76 mg/day and was not significantly different between urban and rural area. Cereals, vegetables, and fruit products were the main food sources of plant sterols in both areas. In addition, a list of several surveyed food items possible to be enriched with plant sterols was developed within the study. These results provide baseline data to develop functional foods fortified with plant sterols suitable for the Indonesian needs and taste. However, further studies are needed to confirm efficacy and safety of introducing such phytosterol-enriched products into a habitual diet, especially considering possible long-term side effects of plant sterol treatment.


Assuntos
Anticolesterolemiantes/análise , Doença das Coronárias/prevenção & controle , Dieta/estatística & dados numéricos , Hipercolesterolemia/prevenção & controle , Fitosteróis/análise , Adulto , Idoso , Colesterol/sangue , Doença das Coronárias/etiologia , Estudos Transversais , Dieta/efeitos adversos , Dieta/métodos , Inquéritos sobre Dietas , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Feminino , Ingredientes de Alimentos , Alimentos Fortificados , Alimento Funcional , Humanos , Hipercolesterolemia/etiologia , Indonésia , Masculino , Pessoa de Meia-Idade
6.
Nutrients ; 12(10)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050310

RESUMO

The present study aimed to determine the effect of an ethyl acetate extract of Mikania micrantha stems (EAMMS) in hypercholesterolemia-induced rats. Rats were divided into a normal group (NC) and hypercholesterolemia induced groups: hypercholesterolemia control group (PC), simvastatin group (SV) (10 mg/kg) and EAMMS extract groups at different dosages of 50, 100 and 200 mg/kg, respectively. Blood serum and tissues were collected for haematological, biochemical, histopathological, and enzyme analysis. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, malondialdehyde (MDA) level, as well as enzymes of HMG-CoA reductase (HMGCR) and acetyl-CoA acetyltransferase 2 (ACAT2), were measured. Feeding rats with high cholesterol diet for eight weeks resulted in a significantly (p < 0.05) increased of TC, TG, LDL-C, AST, ALT and MDA levels. Meanwhile, the administration of EAMMS extract (50, 100 and 200 mg/kg) and simvastatin (10 mg/kg) significantly reduced (p < 0.05) the levels of TC, TG, LDL-C and MDA compared to rats in the PC group. Furthermore, all EAMMS and SV-treated groups showed a higher HDL-C level compared to both NC and PC groups. No significant difference was found in the level of ALT, AST, urea and creatinine between the different dosages in EAMMS extracts. Treatment with EAMMS also exhibited the highest inhibition activity of enzyme HMGCR and ACAT2 as compared to the control group. From the histopathological examination, liver tissues in the PC group showed severe steatosis than those fed with EAMMS and normal diet. Treatment with EAMMS extract ameliorated and reduced the pathological changes in the liver. No morphological changes showed in the kidney structure of both control and treated groups. In conclusion, these findings demonstrated that EAMMS extract has anti-hypercholesterolemia properties and could be used as an alternative treatment for this disorder.


Assuntos
Acetil-CoA C-Acetiltransferase/antagonistas & inibidores , Acetil-CoA C-Acetiltransferase/metabolismo , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Mikania/química , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/etiologia , Masculino , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley
7.
Nutrients ; 12(8)2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32824008

RESUMO

Choline is converted to trimethylamine by gut microbiota and further oxidized to trimethylamine-N-oxide (TMAO) by hepatic flavin monooxygenases. Positive correlation between TMAO and chronic diseases has been reported. Polyphenols in black raspberry (BR), especially anthocyanins, possess various biological activities. The objective of this study was to determine the effects of BR extract on the level of choline-derived metabolites, serum lipid profile, and inflammation markers in rats fed high-fat and high-choline diets. Forty female Sprague-Dawley (SD) rats were randomly divided into four groups and fed for 8 weeks as follows: CON (AIN-93G diet), HF (high-fat diet), HFC (HF + 1.5% choline water), and HFCB (HFC + 0.6% BR extract). Serum levels of TMAO, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and cecal trimethylamine (TMA) level were significantly higher in the HFC than in the HFCB. BR extract decreased mRNA expression of pro-inflammatory genes including nuclear factor-κB (NF-κB), interleukin (IL)-1ß, IL-6, and cyclooxygenase-2 (COX-2), and protein expression of NF-κB and COX-2 in liver tissue. These results suggest that consistent intake of BR extract might alleviate hypercholesterolemia and hepatic inflammation induced by excessive choline with a high-fat diet via lowering elevated levels of cecal TMA and serum TMAO in rats.


Assuntos
Antocianinas/farmacologia , Antocianinas/uso terapêutico , Colina/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Hepatite/dietoterapia , Hipercolesterolemia/dietoterapia , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rubus/química , Animais , Antocianinas/administração & dosagem , Antocianinas/isolamento & purificação , Ceco/metabolismo , Colina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Feminino , Hepatite/etiologia , Hepatite/metabolismo , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Interleucina-1beta/metabolismo , Fígado/metabolismo , Metilaminas/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley
8.
Food Funct ; 11(7): 6091-6103, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32568327

RESUMO

Ursolic acid (UA) is a triterpenoid acid widely abundant in fruits and vegetables such as apple, blueberry and cranberry. The present study was carried out to investigate the effect of UA supplementation in diet on blood cholesterol, intestinal cholesterol absorption and gut microbiota in hypercholesterolemic hamsters. A total of thirty-two hamsters were randomly assigned to four groups and given a non-cholesterol diet (NCD), a high-cholesterol diet containing 0.1% cholesterol (HCD), an HCD diet containing 0.2% UA (UAL), or an HCD diet containing 0.4% UA (UAH) for 6 weeks. Results showed that UA supplementation reduced plasma cholesterol by 15-16% and inhibited intestinal cholesterol absorption by 2.6-9.2%. The in vitro micellar cholesterol solubility experiment clearly demonstrated that UA could displace 40% cholesterol from micelles. In addition, UA decreased the ratio of Firmicutes to Bacteroidetes, whereas it enhanced the growth of short chain fatty acid (SCFA)-producing bacteria in the intestine. In conclusion, UA possessed a cholesterol-lowering activity and could favorably modulate the gut microbiota.


Assuntos
Bactérias/efeitos dos fármacos , Colesterol na Dieta/metabolismo , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Absorção Intestinal/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Bacteroidetes/efeitos dos fármacos , Colesterol na Dieta/efeitos adversos , Colesterol na Dieta/sangue , Cricetinae , Dieta , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Firmicutes/efeitos dos fármacos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Masculino , Mesocricetus , Micelas , Distribuição Aleatória , Solubilidade , Triterpenos/uso terapêutico , Ácido Ursólico
9.
J Complement Integr Med ; 18(1): 67-74, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32554834

RESUMO

BACKGROUND: Dietary phenolic compounds intake have been reported to have an inverse relationship to the prevalence of hypercholesterolemia. The objective of this study is to determine the effect of caffeic acid (CFA) and chlorogenic acid (CGA) on rats fed with high cholesterol diet (HCD). METHODS: Experimental animals were fed with high cholesterol diet (HCD) for a period of 21 days while simvastatin (0.2 mg/kg BWT), CFA and CGA (10 and 15 mg/kg BWT) were administered daily. RESULTS: Activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and arginase were significantly (P<0.05) higher in the rats fed with HCD alone. Also, level of malondiadehyde equivalent compounds (MDA) was significantly (P<0.05) elevated in hypercholesterolemic rats. Nevertheless, treatment with simvastatin, CFA and CGA normalized altered AChE, BChE and arginase activities as well as improved antioxidant status in hypercholesterolemic rats. CONCLUSION: CFA and CGA could offer protective role in hypercholeseterolemic rats via their antioxidant potentials as well as restoring altered activity of acetylcholinesterase, butrylcholinesterase and arginase. Based on our findings chlorogenic acid exhibits better attribute.


Assuntos
Ácidos Cafeicos/administração & dosagem , Ácido Clorogênico/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Hipercolesterolemia/prevenção & controle , Fenóis/administração & dosagem , Acetilcolinesterase/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Arginase/antagonistas & inibidores , Butirilcolinesterase/efeitos dos fármacos , Colesterol/efeitos adversos , Dieta/efeitos adversos , Modelos Animais de Doenças , Hipercolesterolemia/etiologia , Ratos , Sinvastatina/administração & dosagem
10.
Biofactors ; 46(4): 653-664, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32384218

RESUMO

Formation of atherosclerotic plaques, called atherogenesis, is a complex process affected by genetic and environmental factors. It was proposed that endoplasmic reticulum (ER) stress is an important factor in the pathogenesis of atherosclerosis and that vitamin E affects atherosclerotic plaque formation via its antioxidant properties. Here, we investigated ER stress-related molecular mechanisms in high-cholesterol diet (HCD, 2%)-induced atherosclerosis model and the role of vitamin E supplementation in it, beyond its antioxidant properties. The consequences of HCD and vitamin E supplementation were examined by determining protein levels of ER stress markers in aortic tissues. As vitamin E supplementation acts on several unfolded protein response (UPR) factors, it decreased ER stress induced by HCD. To elucidate the associated pathways, gene expression profiling was performed, revealing differentially expressed genes enriched in ER stress-related pathways such as the proteasome and the apoptosis pathways. We further assessed the proteasomal activity impaired by HCD in the aorta and showed that vitamin E reversed it to that of control animals. Overall, the study characterized the effects of HCD and vitamin E on ER stress-related gene expression, revealing the role of proteolytic systems during atherogenesis.


Assuntos
Antioxidantes/farmacologia , Aterosclerose/genética , Colesterol/administração & dosagem , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipercolesterolemia/genética , Placa Aterosclerótica/genética , Vitamina E/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Hipercolesterolemia/etiologia , Hipercolesterolemia/patologia , Hipercolesterolemia/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Anotação de Sequência Molecular , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/prevenção & controle , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Coelhos , Resposta a Proteínas não Dobradas/efeitos dos fármacos
11.
Br J Nutr ; 123(12): 1365-1372, 2020 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-32077392

RESUMO

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.


Assuntos
Emulsões Gordurosas Intravenosas/análise , Hipercolesterolemia/etiologia , Enteropatias/etiologia , Erros Inatos do Metabolismo Lipídico/etiologia , Soluções de Nutrição Parenteral/química , Nutrição Parenteral/efeitos adversos , Fitosteróis/efeitos adversos , Fitosteróis/análise , Adulto , Colesterol/análogos & derivados , Colesterol/análise , Colesterol/sangue , Feminino , Óleos de Peixe/análise , Humanos , Pacientes Internados , Masculino , Óleos de Plantas/análise , Estudos Prospectivos , Estigmasterol/análise , Verduras/química
12.
Nutrients ; 12(2)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050453

RESUMO

Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris®, containing MK-7, magnesium carbonate, and Sucrosomial® Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, i.e. control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial® Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; p < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (-18.9% in supplemental uremic vs. uremic diet; p < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (-38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients.


Assuntos
Colesterol/metabolismo , Suplementos Nutricionais , Hipercolesterolemia/terapia , Insuficiência Renal Crônica/prevenção & controle , Uremia/prevenção & controle , Acil Coenzima A/metabolismo , Adenina , Animais , Anticolesterolemiantes , Linhagem Celular Tumoral , Colesterol/biossíntese , Cisteína/análogos & derivados , Cisteína/metabolismo , Humanos , Hipercolesterolemia/etiologia , Ferro , Magnésio , Masculino , Ratos Sprague-Dawley , Receptores de LDL/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Sinvastatina , Uremia/complicações , Uremia/metabolismo , Uremia/patologia , Calcificação Vascular
13.
J Med Food ; 23(3): 289-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31580748

RESUMO

Obesity reduces the quality of life and life expectancy, whereas nonoperative interventions have shown poor results so far. Statins effectively combat hypercholesterolemia but are not well tolerated at high doses, raising the need for coprescription with cholesterol sorbents and/or absorption inhibitors. Montmorillonite (MMT) clay was found to attenuate hypercholesterolemia and obesity by reducing cholesterol and fat absorption. However, acicular clay-like sepiolite may offer better results due to its more substantial adsorption of nonpolar molecules. We herein aimed at (1) assessing in vitro the capacity of sepiolite to adsorb edible oil and cholesterol compared with that of MMT and (2) assessing in vivo the effect of continuous feeding on a high-fat high-cholesterol diet (HFD) (53.6% w/w fat and 0.2% cholesterol) supplemented with 5% (w/w) edible sepiolite, on diet-induced obesity rate, hypercholesterolemia, and hyperlipidemia. Fourier transform infrared spectroscopy showed in vitro that sepiolite adsorption of olive oil and cholesterol was five to eight times greater than that of MMT clay. Sepiolite supplementation to HFD fed to mature mice for 12.5 weeks resulted in lower total blood cholesterol and triacylglycerol levels and attenuated body weight gain, by reducing fat gain. Sepiolite supplementation did not affect energy intake but increased fecal extraction of sterols and lipids, without notable side effects. These results demonstrate that supplementing a HFD with sepiolite attenuates gastrointestinal absorption of dietary lipids and sterols, thus mitigating obesity, hyperlipidemia, and hypercholesterolemia. Further exploration of the efficacy, mechanism of action, and safety of sepiolite as a food supplement for combating the metabolic syndrome is needed.


Assuntos
Argila/química , Hipercolesterolemia/tratamento farmacológico , Silicatos de Magnésio/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Triglicerídeos/metabolismo , Aumento de Peso/efeitos dos fármacos
14.
J Nutr Sci Vitaminol (Tokyo) ; 65(5): 421-429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666479

RESUMO

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMP-activated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation.


Assuntos
Suplementos Nutricionais , Diosgenina/administração & dosagem , Hipercolesterolemia/terapia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Ácidos e Sais Biliares/análise , Colesterol/análise , HDL-Colesterol/sangue , Dieta Hiperlipídica , Fezes/química , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipertrofia , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Ratos , Coxa da Perna/patologia , Triglicerídeos/análise
15.
Arch Physiol Biochem ; 125(3): 220-227, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29544357

RESUMO

High fat diet (HFD) exposure is associated with various pathological dysfunctions, including haematological disorders and oxidative stress. The in vitro analysis of AECG revealed the presence of important levels of polyphenols and flavonoids, and denoted antioxidant capacities confirmed by nitric oxide radical (NO•), reducing the power and HPLC chemical components' determinations. The animals exposed to HFD revealed a severe damage in the blood cells structure and haematological parameters accompanied with a significant decrease in serum Mg2+ and Ca2+ ATPase activities. Furthermore, malondialdehyde (MDA) and the advanced oxidation of protein products (AOPP) levels were significantly increased, while vitamin C level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were markedly reduced in the erythrocytes and platelets of HFD-treated mice. However, the co-administration of AECG with HFD-treated animals restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Chaetomorpha gracilis extract was a useful element preventing HFD-induced blood cells damage.


Assuntos
Clorófitas/química , Eritrócitos/efeitos dos fármacos , Hipercolesterolemia/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Eritrócitos/patologia , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo
16.
Nutrients ; 10(10)2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30326655

RESUMO

The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv®, an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv® is a polyphenol-rich ingredient obtained from artichoke, olive and grape extracts as part of fruit and vegetables commonly consumed within the Mediterranean diet. A total of 21 Golden Syrian hamsters were divided into three groups. The standard group (STD) was fed a normolipidemic diet for 12 weeks, while the control group (CTRL) and Oleactiv® goup (OLE) were fed a high-fat diet. After sacrifice, the aortic fatty streak area (AFSA), plasmatic total cholesterol (TC), high-density lipoproteins (HDL-C), non-HDL-C and triglycerides (TG), were assessed. The cholesterol efflux capacity (CEC) of hamster plasma was quantified using a radiolabeled technique in murine macrophages J774. OLE administration induced a significant reduction of AFSA (-69%, p < 0.0001). Hamsters of the OLE group showed a significant decrease of both non-HDL-C (-173 mmol/L, p < 0.05) and TG (-154 mmol/L, p < 0.05). Interestingly, OLE induced a significant increase of total CEC (+17,33%, p < 0,05). Oleactiv® supplementation prevented atheroma development and had positive effects on the lipid profile of hypercholesterolemic hamsters. The increased CEC underlines the anti-atherosclerotic mechanism at the root of the atheroma reduction observed.


Assuntos
Anticolesterolemiantes/farmacologia , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Colesterol/sangue , Suplementos Nutricionais , Hipercolesterolemia/tratamento farmacológico , Polifenóis/farmacologia , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Linhagem Celular , HDL-Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Mesocricetus , Camundongos , Placa Aterosclerótica , Triglicerídeos/sangue
17.
Molecules ; 23(4)2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29677105

RESUMO

The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was to identify and quantify the nut oil fatty acids from Attalea phalerata and investigate their metabolic effects in rats with hyperlipidemia induced by a diet rich in fructose. Oleic and lauric acids were the major compounds found in the A. phalerata nut oil (APNO). Hyperlipidemic rats treated with APNO showed a reduction in the total serum cholesterol similar to those treated with simvastatin, an increased body temperature by 1 °C, and a reduction in the body weight gain and mesenteric depot of white adipose tissue compared to the hyperlipidemic controls rats. There was an increase in the relative liver weight of rats treated with APNO, without, however, any change in the serum markers of hepatic toxicity. In addition, there was an increase in the moisture and lipid content of the feces of the rats treated with APNO compared to the controls. Together, these results suggest that APNO has potential use in health foods and nutritional supplements to control hypercholesterolemia and obesity.


Assuntos
Arecaceae/química , Nozes/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Adiposidade/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta , Ácidos Graxos/metabolismo , Frutose , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Compostos Fitoquímicos/química , Ratos
18.
J Physiol Biochem ; 74(1): 189-193, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29374374

RESUMO

Currently, hypothyroidism is usually treated only with drugs; patients are never told that they could regulate their levels of iodine with dietary recommendations in a complementary way. The objective of this work was to explore the effect of a constant iodine intake through the diet in a postmenopausal woman with subclinical grade II hypothyroidism, who also had mild hypercholesterolemia and obesity. Baseline anthropometric nutritional, pharmacological, and habit data were obtained, then the woman was scheduled for 1 month a diet in which she was provided food naturally containing iodine, so that the recommended requirements (iodine 150 µg/day) were met. All the information about which foods contain this mineral was supplied and explained to the patient. This diet was also designed to help her to gradually lose weight, and was more balanced and closer to the nutritional recommendations. The results obtained in this work were satisfactory, having achieved improved blood levels of thyroid-stimulating hormone (1.78 µIU/mL) and reduced total cholesterol levels (198 mg/dL). Statement of hypercholesterolemia was demoted. In addition, a significant improvement in relation to weight and body volume was reached (body mass index fell from 30.13 to 28.5 kg/m2), an important fact since it has impacted the overall well-being of the patient. In conclusion, it was demonstrated that a constant iodine intake through the diet for this patient with grade II hypothyroidism was very effective, and therefore, this aspect should be also considered during hypothyroidism treatment.


Assuntos
Doenças Assintomáticas , Dieta Saudável , Hipotireoidismo/dietoterapia , Iodo/uso terapêutico , Glândula Tireoide/fisiopatologia , Índice de Massa Corporal , Terapia Combinada , Dieta Redutora , Feminino , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/prevenção & controle , Hipotireoidismo/fisiopatologia , Hipotireoidismo/terapia , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/etiologia , Obesidade/prevenção & controle , Educação de Pacientes como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Redução de Peso
19.
Nutr Res ; 46: 31-37, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29173649

RESUMO

Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known. We hypothesized that dietary intake of BM will prevent weight gain and improve lipid profile of C57BL/6 mice fed a high-fat diet (HFD). Mice were fed a HFD supplemented with 5% w/w BM (BM-HFD) for 4 weeks, and then switched to a HFD for 4 weeks. Mice fed a BM-HFD showed significantly lower body weight gain and abdominal fat, compared to the HFD. Furthermore, a BM-HFD significantly reduced plasma and hepatic total and low-density lipoprotein (LDL)-cholesterol, compared to HFD. The decrease in cholesterol levels coincided with inhibition of hepatic sterol regulatory element-binding protein-2 and HMG-CoA reductase mRNA expression, and an increase in LDL-receptor gene expression in the BM-HFD group, compared to the HFD group. In conclusion, our findings have established that BM reduces body weight gain in mice. BM may have potential to lower cholesterol levels by inhibiting cholesterol synthesis, thereby protecting against obesity and perhaps heart disease.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Misturas Complexas/uso terapêutico , Suplementos Nutricionais , Hipercolesterolemia/prevenção & controle , Mytilus edulis/química , Obesidade/prevenção & controle , Adiposidade , Animais , Fármacos Antiobesidade/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , LDL-Colesterol/sangue , Misturas Complexas/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Liofilização , Regulação da Expressão Gênica , Hidroximetilglutaril-CoA Redutases/química , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Resistência à Insulina , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/etiologia , Obesidade/metabolismo , Distribuição Aleatória , Receptores de LDL/agonistas , Receptores de LDL/genética , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/antagonistas & inibidores , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
20.
J Complement Integr Med ; 14(4)2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28731315

RESUMO

Background Lipid profile disturbances are important risk factors for cardiovascular events in patients with diabetes mellitus and finding safe and multifaceted agents is persuaded in this regard. This study aimed to evaluate the effect of cornelian cherry dried powder (CCDP) on serum lipid profile as well as liver antioxidant capacity, HMG-CoA reductase level and activity, and LDL receptor level in streptozotocin-induced diabetic rats. Methods Forty-eight male adult Wistar rats were randomly allocated into eight equal groups and were treated for 4 weeks as follows: negative control (normal rats, basic diet); positive control (diabetic rats, basic diet), T1 to T4 groups: diabetic rats fed with basic diet containing 0.25, 0.5, 1 and 2 g/ 100 g BW CCDP, respectively; T5: diabetic rats fed with basic diet plus 10 mg/kg lovastatin in drinking water and T6: normal rats fed with basic diet containing 1 g/ 100 g BW CCDP. Results Administration of CCDP had no significant effect on serum glucose levels in diabetic rats however decreased total cholesterol, low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) levels and liver antioxidant capacity as compared to positive control rats (p<0.05). Although HMG-CoA reductase level showed a significant decrease only in T3 group, its activity was reduced in all diabetic CCDP and lovastatin-treated groups as compared to positive control. LDL receptor level remained statistically the same among positive control and CCDP-treated groups. Conclusions In conclusion, the present study confirms hypocholesterolemic effect of CCDP in diabetic rats and demonstrated that this effect was at least partly due to inhibition of liver HMG-CoA reductase activity.


Assuntos
Anticolesterolemiantes/uso terapêutico , Colesterol/sangue , Cornaceae , Diabetes Mellitus Experimental/complicações , Hipercolesterolemia/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Glicemia/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Frutas , Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Lovastatina/farmacologia , Lovastatina/uso terapêutico , Masculino , Extratos Vegetais/farmacologia , Pós , Ratos Wistar
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