Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 104
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Pflugers Arch ; 476(3): 283-293, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38044359

RESUMO

High-fat diet (HFD) feeding in rodents has become an essential tool to critically analyze and study the pathological effects of obesity, including mitochondrial dysfunction and insulin resistance. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates cellular energy metabolism to influence insulin sensitivity, beyond its active role in stimulating mitochondrial biogenesis to facilitate skeletal muscle adaptations in response to HFD feeding. Here, some of the major electronic databases like PubMed, Embase, and Web of Science were accessed to update and critically discuss information on the potential role of PGC-1α during metabolic adaptations within the skeletal muscle in response to HFD feeding in rodents. In fact, available evidence suggests that partial exposure to HFD feeding (potentially during the early stages of disease development) is associated with impaired metabolic adaptations within the skeletal muscle, including mitochondrial dysfunction and reduced insulin sensitivity. In terms of implicated molecular mechanisms, these negative effects are partially associated with reduced activity of PGC-1α, together with the phosphorylation of protein kinase B and altered expression of genes involving nuclear respiratory factor 1 and mitochondrial transcription factor A within the skeletal muscle. Notably, metabolic abnormalities observed with chronic exposure to HFD (likely during the late stages of disease development) may potentially occur independently of PGC-1α regulation within the muscle of rodents. Summarized evidence suggests the causal relationship between PGC-1α regulation and effective modulations of mitochondrial biogenesis and metabolic flexibility during the different stages of disease development. It further indicates that prominent interventions like caloric restriction and physical exercise may affect PGC-1α regulation during effective modulation of metabolic processes.


Assuntos
Resistência à Insulina , Doenças Mitocondriais , Animais , Dieta Hiperlipídica , Músculo Esquelético/metabolismo , Modelos Animais , Doenças Mitocondriais/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
2.
Curr Issues Mol Biol ; 45(8): 6216-6245, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37623211

RESUMO

Type 2 diabetes (T2D) is characterized by pancreatic beta-cell dysfunction, increased cell death and loss of beta-cell mass despite chronic treatment. Consequently, there has been growing interest in developing beta cell-centered therapies. Beta-cell regeneration is mediated by augmented beta-cell proliferation, transdifferentiation of other islet cell types to functional beta-like cells or the reprograming of beta-cell progenitors into fully differentiated beta cells. This mediation is orchestrated by beta-cell differentiation transcription factors and the regulation of the cell cycle machinery. This review investigates the beta-cell regenerative potential of antidiabetic plant extracts and phytochemicals. Various preclinical studies, including in vitro, in vivo and ex vivo studies, are highlighted. Further, the potential regenerative mechanisms and the intra and extracellular mediators that are of significance are discussed. Also, the potential of phytochemicals to translate into regenerative therapies for T2D patients is highlighted, and some suggestions regarding future perspectives are made.

3.
Biochem Biophys Res Commun ; 680: 25-33, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37713959

RESUMO

Previously we reported that a high fat, high sugar (HFHS) diet induced adiposity, hyperinsulinaemia, hyperleptinaemia, hypertriglyceridaemia and increased liver mass in male Wistar rats. In the present study, the mechanisms underlying the increased liver mass were further elucidated by assessing hepatic lipid accumulation and the expression and methylation status of key metabolic genes using histology, quantitative real-time PCR and pyrosequencing, respectively. The HFHS diet induced hepatic steatosis, increased hepatic triglycerides (1.8-fold, p < 0.001), and increased the expression of sterol regulatory element-binding transcription factor 1 (Srebf1) (2.0-fold, p < 0.001) and peroxisome proliferator-activated receptor gamma (Pparg) (1.7-fold, p = 0.017) in the liver. The expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc1a) was decreased (2.6-fold, p < 0.010), which was accompanied by hypermethylation (p = 0.018) of a conserved CpG site in the promoter of Pgc1a in HFHS fed rats compared to controls. In silico analysis identified putative binding sites for CCAAT/enhancer-binding protein beta (C/EBPß) and hepatocyte nuclear factor 1 (HNF1) within proximity to the hypermethylated CpG. As Pgc1a is a co-activator of several transcription factors regulating multiple metabolic pathways, hypermethylation of this conserved CpG site in the promoter of Pgc1a may be one possible mechanism contributing to the development of hepatic steatosis in response to a HFHS diet. However, further work is required to confirm the role of Pgc1a in steatosis.

4.
Pharmacol Res ; 196: 106918, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37703962

RESUMO

There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.

5.
J Water Health ; 21(3): 402-408, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37338319

RESUMO

Monitoring of SARS-CoV-2 RNA in wastewater has revealed the role of mobility in the transmission of coronavirus disease (COVID-19), and the surveillance of airport wastewater in cities across the world has demonstrated how travel entry points can give an indication of trends in transmission. This study undertook wastewater surveillance at the Cape Town International Airport (CTIA) to assess the use of a WBE approach to provide supplementary information on the presence of COVID-19 at a key air travel entry point in South Africa. Grab wastewater samples (n = 55) were collected from the CTIA wastewater pump station and analysed using quantitative real-time polymerase chain reaction (qRT-PCR) method. The study found a correlation between the wastewater data and clinical cases reported in the City of Cape Town during various time periods and during the peak of a COVID-19 wave. Highly elevated viral loads in the wastewater were observed at times there was increased mobility through the airport. The study also revealed elevated viral load levels at the airport despite the stricter restrictions and through the lower restrictions. The study findings indicate wastewater surveillance and airports can provide supplementary information to airport authorities to assess the impacts of imposed travel restrictions.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Águas Residuárias , Aeroportos , Cidades , RNA Viral , Vigilância Epidemiológica Baseada em Águas Residuárias , África do Sul/epidemiologia
6.
J Infect Dis ; 226(8): 1418-1427, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36017801

RESUMO

This study was one of the first to detect Omicron sublineages BA.4 and BA.5 in wastewater from South Africa. Spearman rank correlation analysis confirmed a strong positive correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in wastewater samples and clinical cases (r = 0.7749, P < .0001). SARS-CoV-2 viral load detected in wastewater, resulting from the Delta-driven third wave, was significantly higher than during the Omicron-driven fourth wave. Whole-genome sequencing confirmed presence of Omicron lineage defining mutations in wastewater with the first occurrence reported 23 November 2021 (BA.1 predominant). The variant spread rapidly, with prevalence of Omicron-positive wastewater samples rising to >80% by 10 January 2022 with BA.2 as the predominant sublineage by 10 March 2022, whilst on 18 April 2022 BA.4 and BA.5 were detected in selected wastewater sites. These findings demonstrate the value of wastewater-based epidemiology to monitor the spatiotemporal spread and potential origin of new Omicron sublineages.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Prevalência , RNA Viral/genética , SARS-CoV-2/genética , África do Sul/epidemiologia , Águas Residuárias
7.
Int J Mol Sci ; 23(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35887112

RESUMO

There are three main types of diabetes, namely, type 1 diabetes, type 2 diabetes (T2D), and diabetes in pregnancy (gestational diabetes) [...].


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Feminino , Alimentos , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Gravidez
8.
Molecules ; 27(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36432195

RESUMO

Diabetes, a prevalent metabolic condition with a wide range of complications, is fast becoming a global health crisis. Herbal medicine and enhanced extracts are some of the therapeutic options used in the management of diabetes mellitus. The plant-derived molecules and their suitable structure modification have given many leads or drugs to the world such as metformin used as an antidiabetic drug. The stem extract of Sclerocarya birrea has been reported as a potent antidiabetic (glucose uptake) agent. However, the bioactive compounds have not been reported from S. birrea for treatment of diabetes. In this study, the spray-dried aqueous leaf extracts of S. birrea were investigated as an antidiabetic agent using a 2-deoxy-glucose (2DG) technique showing good stimulatory effect on glucose uptake in differentiated C2C12 myocytes with % 2DG uptake ranging from 110-180% that was comparable to the positive control insulin. Three compounds were isolated and identified using bioassay-guided fractionation of the spray-dried aqueous extract of S. birrea leaves: myricetin (1), myricetin-3-O-ß-D-glucuronide (2) and quercetin-3-O-ß-D-glucuronide (3). Their chemical structures were determined using NMR and mass spectrometric analyses, as well as a comparison of experimentally obtained data to those reported in the literature. The isolated compounds (1-3) were studied for their stimulatory actions on glucose uptake in differentiated C2C12 myocytes. The three compounds (1, 2 and 3) showed stimulatory effects on the uptake of 2DG in C2C12 myocytes with % 2DG uptake ranging from 43.9-109.1% that was better compared to the positive control insulin. Additionally, this is the first report of the flavonoid glycosides (myricetin-3-O-ß-D-glucuronide) for antidiabetic activity and they are the main bioactive compound in the extract responsible for the antidiabetic activity. This result suggests that the S. birrea leaves have the potential to be developed for treatment of diabetes.


Assuntos
Anacardiaceae , Diabetes Mellitus , Hipoglicemiantes/química , Extratos Vegetais/química , Anacardiaceae/química , Insulina , Diabetes Mellitus/tratamento farmacológico , Glucose/metabolismo
9.
Heart Fail Rev ; 26(6): 1437-1445, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-32157481

RESUMO

Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure-related outcomes remains inconclusive. The current systematic review explored evidence from randomized clinical trials (RCTs) reporting on the impact of metformin in modulating heart failure-related markers in patients with or without T2D. Electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible studies. Included studies were those assessing the use of metformin as an intervention, and also containing the comparison group on placebo, and all articles had to report on measurable heart failure-related indices in individuals with or without T2D. The modified Downs and Black checklist was used to evaluate the risk of bias. Overall, nine studies met the inclusion criteria, enrolling a total of 2486 patients. Although summarized evidence showed that metformin did not affect left ventricular function, this antidiabetic drug could improve myocardial oxygen consumption concomitant to reducing prominent markers of heart failure such as n-terminal pro-brain natriuretic peptide and low-density lipoprotein levels, inconsistently between diabetic and nondiabetic patients. Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11). Overall, although such beneficial effects were observed with metformin treatment, additional RCTs are necessary to improve our understanding on its modulatory effects on heart failure-related outcomes especially in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Metformina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Int J Mol Sci ; 23(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35008779

RESUMO

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D.


Assuntos
Chalconas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Animais , Disponibilidade Biológica , Biotransformação , Chalconas/química , Chalconas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Resultado do Tratamento
11.
Molecules ; 26(7)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801575

RESUMO

Momordica balsamina leaf extracts originating from three different geographical locations were analyzed using reversed-phase liquid chromatography (RP-LC) coupled to travelling wave ion mobility (TWIMS) and high-resolution mass spectrometry (HRMS) in conjunction with chemometric analysis to differentiate between potential chemotypes. Furthermore, the cytotoxicity of the three individual chemotypes was evaluated using HT-29 colon cancer cells. A total of 11 molecular species including three flavonol glycosides, five cucurbitane-type triterpenoid aglycones and three glycosidic cucurbitane-type triterpenoids were identified. The cucurbitane-type triterpenoid aglycones were detected in the positive ionization mode following dehydration [M + H - H2O]+ of the parent compound, whereas the cucurbitane-type triterpenoid glycosides were primarily identified following adduct formation with ammonia [M + NH4]+. The principle component analysis (PCA) loadings plot and a variable influence on projection (VIP) analysis revealed that the isomeric pair balsaminol E and/or karavilagen E was the key molecular species contributing to the distinction between geographical samples. Ultimately, based on statistical analysis, it is hypothesized that balsaminol E and/or karavilagen E are likely responsible for the cytotoxic effects in HT-29 cells.


Assuntos
Antineoplásicos Fitogênicos/química , Flavonóis/química , Glicosídeos/química , Momordica/química , Triterpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia de Fase Reversa , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HT29 , Humanos , Concentração Inibidora 50 , Espectrometria de Massas/métodos , Extratos Vegetais/química , Folhas de Planta/química , Análise de Componente Principal , Relação Estrutura-Atividade , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
12.
Molecules ; 26(20)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34684871

RESUMO

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.


Assuntos
Antimicina A/toxicidade , Aspalathus/química , Chalconas/farmacologia , Flavonoides/farmacologia , Glucosídeos/farmacologia , Luteolina/farmacologia , Mitocôndrias/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Animais , Antibacterianos/toxicidade , Linhagem Celular , Células Cultivadas , Camundongos , Mitocôndrias/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Chá/química
13.
Molecules ; 26(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684734

RESUMO

Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes.


Assuntos
Flavonoides/farmacologia , Glucosídeos/farmacologia , Insulina/genética , Aspalathus/química , Linhagem Celular , Chalconas/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glucosídeos/metabolismo , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
14.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068459

RESUMO

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.


Assuntos
Músculo Esquelético/metabolismo , Polifenóis/farmacologia , Animais , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Humanos , Músculo Esquelético/efeitos dos fármacos , Polifenóis/química
15.
J Cell Physiol ; 235(12): 9487-9496, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32458430

RESUMO

Rooibos (Aspalathus linearis) has various health benefits. Two case studies have associated chronic Rooibos consumption with conventional prescription medications, including atorvastatin (ATV), with hepatotoxicity. Statins act by inhibiting hydroxymethylglutaryl-coenzyme A reductase, a rate-limiting enzyme in cholesterol synthesis. Although rare, statins are potentially hepatotoxic. The aim was to investigate interactions between aspalathin-rich Rooibos extract GRT™ and ATV-induced hepatotoxicity in C3A liver cells cultured with and without palmitate. Effects of co-treatment of GRT + ATV on cell viability, oxidative stress, apoptosis, mitochondrial integrity, and cellular reactive oxygen species (ROS) production were assessed. Significantly increased ROS production was observed in cells exposed to ATV and palmitate. Combination therapy of GRT + ATV also showed significant increases in ROS production. Under palmitate-treated conditions, ATV-induced significant apoptosis which was not ameliorated by GRT + ATV co-treatment. Despite studies purporting hepatoprotection from Rooibos, our study showed that GRT was unable to modulate ATV-induced hepatotoxic effects in this model.


Assuntos
Atorvastatina/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Fígado/efeitos dos fármacos , Fitoterapia/métodos , Espécies Reativas de Oxigênio/metabolismo
16.
Pharmacol Res ; 158: 104867, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32407953

RESUMO

Isoorientin is a natural C-glucosyl flavone that is generating a lot of interest due to its multiple pharmacological activities. Increasing experimental data have shown that the robust antioxidant and anti-inflammatory properties of isoorientin remain important in ameliorating a number of metabolic complications. In fact, plants rich in isoorientin have demonstrated strong ameliorative properties against complications such as hyperglycemia, hyperlipidemia, and insulin resistance. However, while such evidence is accumulating, it has not been reviewed to better inform on the therapeutic potential of this flavone in improving human health. This review examines and extrapolates available literature on the potential beneficial or detrimental effects associated with the use of isoorientin in mitigating metabolic diseases, with a specific focus on diabetes, obesity, and insulin resistance, including associated complications. The discussion includes effective doses in various experimental settings and proposed molecular mechanisms by which isoorientin may exert its therapeutic effects. In addition, the protective effects of extracts of a number of isoorientin-rich plants against metabolic complications will be highlighted.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/uso terapêutico , Luteolina/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Animais , Diabetes Mellitus/dietoterapia , Diabetes Mellitus/tratamento farmacológico , Dieta , Humanos , Resistência à Insulina , Doenças Metabólicas/dietoterapia , Estresse Oxidativo/efeitos dos fármacos
17.
Phytother Res ; 34(7): 1519-1529, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32017271

RESUMO

The increased use of herbal supplements as complementary or alternative medicines has become a clinical conundrum due to the potential for herb-drug interactions. This is exacerbated by an increased supply of new herbal supplements in the market claiming various health advantages. These herbal supplements are available as over-the-counter self-medications. Herbal supplements are generally perceived as efficacious without side effects commonly associated with conventional drugs. However, despite regulations, claims related to their therapeutic effects are mostly unsupported by scientific evidence. These products often lack suitable product quality controls, labelled inadequately and with batch to batch variations, potentially compromising the safety of the consumer. Amongst health practitioners, the greatest concern is related to the lack of chemical characterization of the active compounds of the herbal supplements. The interaction between these different active components and their concomitant effects on other conventional drugs is generally not known. This review will focus on herbal supplements with the potential to effect pharmacokinetic and pharmacodynamic properties of oestrogen-based oral contraceptives. The use of herbal supplements for weight management, depression, and immune boosting benefits were selected as likely herbal supplements to be used concomitantly by women on oral contraceptives.


Assuntos
Anticoncepcionais Orais/química , Suplementos Nutricionais/análise , Estrogênios/metabolismo , Interações Ervas-Drogas/fisiologia , Feminino , Humanos , Masculino
18.
Int J Mol Sci ; 21(9)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32375340

RESUMO

Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.


Assuntos
Adipocinas/metabolismo , Biomarcadores , Suplementos Nutricionais , Peroxidação de Lipídeos/efeitos dos fármacos , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Ubiquinona/análogos & derivados , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Viés de Publicação , Ubiquinona/administração & dosagem
19.
Molecules ; 25(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32294890

RESUMO

The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1-100 µM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 µM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Luteolina/farmacologia , Mitocôndrias/efeitos dos fármacos , Obesidade/metabolismo , Células 3T3-L1 , Quinases Proteína-Quinases Ativadas por AMP , Trifosfato de Adenosina/metabolismo , Adipócitos/metabolismo , Animais , Dioxóis/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Insulina/farmacologia , Isoproterenol/farmacologia , Metformina/farmacologia , Camundongos , Mitocôndrias/metabolismo , Obesidade/tratamento farmacológico , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Heart Fail Rev ; 24(1): 155-166, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30167929

RESUMO

The epidemic of cardiovascular diseases is a global phenomenon that is exaggerated by the growing prevalence of diabetes mellitus. Coronary artery disease and diabetic cardiomyopathy are the major cardiovascular complications responsible for exacerbated myocardial infarction in diabetic individuals. Increasing research has identified hyperglycemia and hyperlipidemia as key factors driving the augmentation of oxidative stress and a pro-inflammatory response that usually results in increased fibrosis and reduced cardiac efficiency. While current antidiabetic agents remain active in attenuating diabetes-associated complications, overtime, their efficacy proves limited in protecting the hearts of diabetic individuals. This has led to a considerable increase in the number of natural products that are screened for their antidiabetic and cardioprotective properties. These natural products may present essential ameliorative properties relevant to their use as a monotherapy or as an adjunct to current drug agents in combating diabetes and its associated cardiovascular complications. Recent findings have suggested that triterpenes isolated from Protorhus longifolia (Benrh.) Engl., a plant species endemic to Southern Africa, display strong antioxidant and antidiabetic properties that may potentially protect against diabetes-induced cardiovascular complications. Thus, in addition to discussing the pathophysiology associated with diabetes-induced cardiovascular injury, available evidence pertaining to the cardiovascular protective potential of lanosteryl triterpenes from Protorhus longifolia will be discussed.


Assuntos
Anacardiaceae/química , Cardiotônicos/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Lanosterol/análogos & derivados , Extratos Vegetais/farmacologia , Animais , Cardiotônicos/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Complicações do Diabetes , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Modelos Animais de Doenças , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Lanosterol/farmacologia , Lanosterol/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA