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Special Issue "Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 March 2018

Special Issue Editor

Guest Editor
Dr. Natalie Ward

School of Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University Western Australia, Perth 6102, Australia
Website | E-Mail
Interests: cardiovascular disease; metabolic syndrome and type 2 diabetes; vascular function; atherosclerosis; nutrition and dietary components; dietary polyphenols; dietary nitrate; gut microbiome

Special Issue Information

Dear Colleagues,

Metabolic syndrome is defined as a series of risk factors that commonly cluster together, increasing the risk of both type 2 diabetes and cardiovascular disease. Several factors contribute to the development of metabolic syndrome, including poor diet, physical inactivity, age, and genetics. Despite the range of pharmacotherapies that exist to treat the various risk factors associated with metabolic syndrome, there remains a strong need to identify other bioactive compounds that may contribute towards reducing overall risk. These may be individual dietary components, marine-based compounds or newly identified products. This Special Issue aims to identify and review the latest bioactive compounds that have been demonstrated to have a beneficial effect on metabolic syndrome and its risk factors.

Dr. Natalie Ward
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bioactive Compounds
  • Metabolic syndrome
  • Type 2 diabetes
  • Diet & dietary components
  • Nutrients
  • Gut microbiome

Published Papers (11 papers)

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Research

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Open AccessArticle Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End Product Formation and Key Enzymes Related to Metabolic Syndrome
Molecules 2017, 22(10), 1785; doi:10.3390/molecules22101785
Received: 26 September 2017 / Revised: 14 October 2017 / Accepted: 16 October 2017 / Published: 21 October 2017
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Abstract
Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase,
[...] Read more.
Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 μg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 ± 1.5 μg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC50 = 362.3 ± 9.2 μg/mL) and α-amylase (IC50 = 119.0 ± 17.7 μg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC50 = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC50 = 626.6 ± 15.0 μg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5–0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat
Molecules 2017, 22(10), 1782; doi:10.3390/molecules22101782
Received: 28 August 2017 / Revised: 9 October 2017 / Accepted: 19 October 2017 / Published: 21 October 2017
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Abstract
Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE)
[...] Read more.
Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) on blood glucose and function of the retina with electroretinography (ERG) in a diabetic setting with or without ischemia-reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove that the SCSE has a retinoprotective effect in diabetic rats: according to ERG measurements, SCSE treatment mitigated the retinal function-damaging effect of diabetes, and proved to be protective in the diabetic eye against ischemia-reperfusion injuries of the retina. Outcomes suggest that the protective effects of SCSE may occur through several pathways, including HO-1 dependent mechanisms. The observation that SCSE treatment decreases blood glucose is also novel. These findings offer the possibility for development of novel therapeutic strategies utilizing this emerging functional food, in particular in the prevention of conditions resulting from high blood glucose or I/R injury, such as deterioration of retinal microcirculation. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle Alpha-Galacto-Oligosaccharides at Low Dose Improve Liver Steatosis in a High-Fat Diet Mouse Model
Molecules 2017, 22(10), 1725; doi:10.3390/molecules22101725
Received: 31 August 2017 / Revised: 10 October 2017 / Accepted: 11 October 2017 / Published: 14 October 2017
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Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that
[...] Read more.
Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that they would exert benefits on the development of metabolic syndrome and associated NAFLD in a rodent model. C57Bl/6J mice were fed a high-fat diet until they developed metabolic syndrome and were then orally treated either with α-GOS at a physiological dose (2.2 g/kg BW/d) or the vehicle over 7 weeks. α-GOS induced a reduction in food intake, but without affecting body weight during the first week of treatment, when compared to the vehicle. Fasting glycaemia was improved after 4 weeks of treatment with α-GOS, whereas insulin sensitivity (assessed with HOMA-IR) was unaffected at the end of the experiment. Plasma non-esterified fatty acids, low-density lipoprotein (LDL) and total cholesterol were lowered by α-GOS while high-density lipoprotein (HDL) and triglycerides levels remained unaffected. α-GOS markedly improved liver steatosis as well as free fatty acid and triglyceride accumulation in the liver. α-GOS improved plasma lipids and prevented NAFLD development through mechanisms which are independent of body weight management and glycemic control. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats
Molecules 2017, 22(10), 1702; doi:10.3390/molecules22101702
Received: 7 September 2017 / Accepted: 3 October 2017 / Published: 12 October 2017
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Abstract
The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum
[...] Read more.
The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007–2012 Korea National Health and Nutrition Examination Survey
Molecules 2017, 22(10), 1664; doi:10.3390/molecules22101664
Received: 31 August 2017 / Revised: 29 September 2017 / Accepted: 2 October 2017 / Published: 5 October 2017
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Abstract
Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national
[...] Read more.
Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national representative data. A total of 24,377 adults (19–74 years) who completed one-day 24 h dietary recall and health examination were included. Dietary antioxidant intakes including α-carotene (p < 0.0001), lycopene (p = 0.0107), flavan-3-ols (p < 0.0001), and proanthocyanidins (p = 0.0075) were significantly higher in non-diabetic subjects than in diabetic subjects. After adjusting for confounding variables, the highest quartile group of α-carotene intake was associated with a 48% reduced risk of T2D in men (OR: 0.52, 95% CI: 0.34–0.80, p for trend = 0.0037) and a 39% reduced risk in women (OR: 0.61, 95% CI: 0.38–0.996, p for trend = 0.0377) compared to the lowest quartile group. Men in the highest quartile of β-carotene intake showed lower risk of T2D (OR: 0.64, 95% CI: 0.42–0.97), but no significant decreasing trend. However, the intakes of total carotenoids and other antioxidants showed no significant association with the risk of T2D. These findings suggest that a further comprehensive approach which considers overall dietary pattern is required. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
Open AccessCommunication Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes
Molecules 2017, 22(9), 1423; doi:10.3390/molecules22091423
Received: 2 August 2017 / Revised: 22 August 2017 / Accepted: 25 August 2017 / Published: 28 August 2017
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Abstract
Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA)
[...] Read more.
Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir
Molecules 2017, 22(8), 1274; doi:10.3390/molecules22081274
Received: 12 July 2017 / Revised: 25 July 2017 / Accepted: 26 July 2017 / Published: 30 July 2017
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Abstract
The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy
[...] Read more.
The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19), and adiponectin, Δw(21), were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines—the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessArticle High-Resolution Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of PTP1B Inhibitors from Vietnamese Plants
Molecules 2017, 22(7), 1228; doi:10.3390/molecules22071228
Received: 27 June 2017 / Revised: 18 July 2017 / Accepted: 19 July 2017 / Published: 20 July 2017
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Abstract
Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18
[...] Read more.
Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18 different plant species were investigated for PTP1B inhibitory activity in vitro. The most promising one, the EtOAc extract of Ficus racemosa, was investigated by high-resolution PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR analysis. This led to the identification of isoderrone (1), derrone (2), alpinumisoflavone (3) and mucusisoflavone B (4) as PTP1B inhibitors. IC50 of these compounds were 22.7 ± 1.7, 12.6 ± 1.6, 21.2 ± 3.8 and 2.5 ± 0.2 µM, respectively. Kinetics analysis revealed that these compounds inhibited PTP1B non-competitively with Ki values of 21.3 ± 2.8, 7.9 ± 1.9, 14.3 ± 2.0, and 3.0 ± 0.5 µM, respectively. These findings support the important role of F. racemosa as a novel source of new drugs and/or as a herbal remedy for treatment of type 2 diabetes. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Review

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Open AccessReview Pharmabiotics as an Emerging Medication for Metabolic Syndrome and Its Related Diseases
Molecules 2017, 22(10), 1795; doi:10.3390/molecules22101795
Received: 31 August 2017 / Revised: 17 October 2017 / Accepted: 20 October 2017 / Published: 24 October 2017
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Abstract
Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with central obesity, hyperglycemia, insulin resistance, dyslipidemia and high blood pressure. In recent decades, because of the remarkable increase in both prevalence and severity, MetS and its related diseases such as cardiovascular
[...] Read more.
Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with central obesity, hyperglycemia, insulin resistance, dyslipidemia and high blood pressure. In recent decades, because of the remarkable increase in both prevalence and severity, MetS and its related diseases such as cardiovascular diseases (CVDs), obesity, hypertension and diabetes have become the main global burden and challenge in strategic management involving prevention and treatment. However, currently, the preventions and treatments based on pharmaceutical interventions do not provide a solution for MetS and its related diseases. Recently, gut microbiota showed clear evidence of preventing and/or treating MetS, shedding light on treating MetS and its related diseases through a completely different approach. In this review, we will interpret the effects of current pharmaceutical drugs used in preventing and treating MetS and its related diseases to understand remaining issues of those interventions. We will explore the possibility of developing gut microbiota as pharmabiotics in a completely new medication option for treating MetS and its related diseases. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessReview Hop Phytochemicals and Their Potential Role in Metabolic Syndrome Prevention and Therapy
Molecules 2017, 22(10), 1761; doi:10.3390/molecules22101761
Received: 31 August 2017 / Revised: 14 October 2017 / Accepted: 17 October 2017 / Published: 19 October 2017
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Abstract
Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN),
[...] Read more.
Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN), are substances with hypoglycemic, antihyperlipidemic, and antiobesity activities. Iso-α-acids (IAA) and matured hop bitter acids (MHBA) improve health by influencing lipid metabolism, glucose tolerance, and body weight. The modulatory effect of IAA and MHBA on lipid metabolism may also be responsible for a loss in body weight. These results suggest promising applications for IAA, MHBA, and XN in humans, particularly in the prevention of diet-induced obesity and diabetes. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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Open AccessReview Olive Polyphenols and the Metabolic Syndrome
Molecules 2017, 22(7), 1082; doi:10.3390/molecules22071082
Received: 22 May 2017 / Accepted: 23 June 2017 / Published: 29 June 2017
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Abstract
Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role
[...] Read more.
Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
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