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The effects of resveratrol on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease

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Abstract

This study was performed to investigate the effects of resveratrol on metabolic status in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was performed in 56 patients with T2DM and CHD. Patients were randomly divided into two groups to receive either 500 mg resveratrol/day (n=28) or placebo (n=28) for 4 weeks. Resveratrol reduced fasting glucose (β -10.04 mg/dL; 95% CI, -18.23, -1.86; P=0.01), insulin (β -1.09 µIU/mL; 95% CI, -1.93, -0.24; P=0.01) and insulin resistance (β -0.48; 95% CI, -0.76, -0.21; P=0.001), and significantly increased insulin sensitivity (β 0.006; 95% CI, 0.001, 0.01; P=0.02) when compared with the placebo. Resveratrol also significantly increased HDL-cholesterol levels (β 3.38 mg/dL; 95% CI, 1.72, 5.05; P<0.001) and significantly decreased total-/HDL-cholesterol ratio (β -0.36; 95% CI, -0.59, -0.13; P=0.002) when compared with the placebo. Additionally, resveratrol caused a significant increase in total antioxidant capacity (TAC) (β 58.88 mmol/L; 95% CI, 17.33, 100.44; P=0.006) and a significant reduction in malondialdehyde (MDA) levels (β -0.21 µmol/L; 95% CI, -0.41, -0.005; P=0.04) when compared with the placebo. Resveratrol upregulated PPAR-γ (P=0.01) and sirtuin 1 (SIRT1) (P=0.01) in peripheral blood mononuclear cell (PBMC) of T2DM patients with CHD. Resveratrol supplementation did not have any effect on inflammatory markers. 4-week supplementation with resveratrol in patients with T2DM and CHD had beneficial effects on glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, TAC and MDA levels. Resveratrol also upregulated PPAR-γ and SIRT1 in PBMC of T2DM patients with CHD.

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... Among patients with T2DM, SIRT-1 protein levels were also significantly increased at the end of 12 weeks of intervention with RSV (3.000 mg/day), compared to the placebo group (2.01 ± 0.64 arbitrary units (AU) vs. 0.86 ± 0.38 AU; p = 0.016) [33]. Also, RSV on a dosage of 500 mg/day upregulated SIRT-1 gene expression in PBMC of T2DM subjects with CHD at the end of 4 weeks [34]. Moreover, subjects with T2DM receiving a RSV (500 mg/day) for 24 weeks showed higher increases in SIRT-1 gene expression/protein levels than placebo and those who received RSV dosage of 40 mg/day [35]. ...
... This can be explained by the mechanism that SIRT1 uses to increase PGC1-α stability and activity through deacetylation and not via increased synthesis [33]. In addition, RSV upregulated PPAR-γ in PBMC of T2DM patients with CHD [34]. On the other hand, KJAER et al. [26] found that RSV treatment did not alter the expression of the mitochondrial biogenesis-related genes SIRT-1, NRF1, AMPK, or TFAM in SAT or striated muscle. ...
... In individuals with obesity and MetS, there was no effect of RSV on body weight or body fat, despite positive metabolic changes [25,26,[33][34][35]. However, body weight, BMI, and WC had reduced in the RSV group compared to baseline values among NAFLD subjects and waist to hip ratio (WHR) was reduced in participants only in the CR diet group. ...
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PurposeHuman sirtuins can be a powerful therapeutic target in preventing and treating obesity and age-related diseases. Some dietary components can modulate sirtuins’ activity, such as resveratrol. This systematic review aimed to assess whether resveratrol (RSV), without other interventions, can stimulate sirtuins in the treatment of excess weight and its comorbidities.MethodsMEDLINE/Pubmed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were used for search eligible articles. Randomized clinical trials assessing RSV supplementation on changes in the sirtuins’ gene expression/protein levels was the primary outcome. Other possible changes in cardiometabolic markers were considered the second outcome. Following PRISMA guidelines and using predefined inclusion and exclusion criteria, two reviewers independently and in parallel screened, assessed the studies' quality, and compiled data. Disagreements were resolved by consensus or consulting a third author.ResultsThis review included seven randomized control trials. Four articles demonstrated a significant increase in SIRT-1 with different RSV dosages and interventions time. The secondary outcomes showed improvements in insulin sensitivity, lipid profile, metabolic flexibility, total antioxidant capacity, energy expenditure changes, and reduction of ectopic accumulation of fat.Conclusion Data from RCTs studies showed that RSV supplementation could stimulate SIRT-1 in humans, and therefore contribute to the treatment of excess weight and its comorbidities. However, more research is needed because it was not possible to confirm this effect truly. [PROSPERO registration number: CRD42020205571]
... This occurs due to the antioxidant capacity of RV and its interaction with cell signaling pathways for the modulation of gene expression. However, other investigations show the lack of a therapeutic effect of this nutraceutical [19,[22][23][24][25]27,29,[33][34][35][61][62][63]. This means that researchers need to continue conducting clinical trials and analyzing existing ones to identify the efficacy and safety of RV as a complementary treatment for NCDs. ...
... According to the analysis by the presence or absence of T2DM, we observed that RV consumption had a positive effect on the four measured parameters (glucose, insulin, HOMA-IR, and HbA1c), in favor of the subjects with T2DM, which was consistent with the majority of the results from clinical trials conducted in diabetic subjects that were included in the meta-analysis ( [18,22,35,36,38,41,44]. They observed a significant decrease in glycemic control markers after RV consumption in diabetic subjects. ...
... However, in the clinical trials included in our metaanalysis, which were conducted in subjects under 45 [19,25,33,43]), it was observed that glycemic control markers did not change. Moreover, among clinical trials with people older than 60 years, only Hoseini et al. [35] reported a significant change in glucose levels after an intervention with 500 mg/day of RV for 4 weeks. Most of the studies where the age of the participants ranged between 45 and 59 years found significant changes in the biomarkers of glycemic control, except those with low doses of RV (Kantartzis et al. [37]) or short intervention periods (Dash et al. [29]). ...
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Resveratrol (RV) is a polyphenolic compound with antioxidant, anti-inflammatory, and hypoglycemic properties. Several in vitro and animal model studies have demonstrated the beneficial effects of RV; however, the results in humans are not conclusive. After a search of different databases, 32 studies were selected for this systematic review and 30 were included in the meta-analysis. Studies that evaluated the effect of RV on glucose, insulin, HbA1c, and insulin resistance (HOMA-IR) levels were included. A significant decrease of glucose (−5.24 mg/dL, p = 0.002) and insulin levels (−1.23 mIU/L, p = 0.0003) was observed. HbA1c and HOMA-IR did not show significant changes. Due to heterogeneity, sub-analyzes were performed. Sub-analysis by dose revealed that glucose levels improve significantly after the administration of 500–1000 mg/day of RV (−7.54 mg/dL, p = 0.002), while insulin improves with doses lower than 500 mg/day (−1.43 mIU/L, p = 0.01) and greater than 1000 mg/day (−2.12 mIU/L, p = 0.03). HbA1c and HOMA-IR remained unchanged after sub-analysis by dose. Our findings suggest that RV improves glucose and insulin levels in subjects with type 2 diabetes mellitus (T2DM) and aged 45–59 years, regardless of the duration of the intervention. HbA1c improves with interventions ≥3 months. HOMA-IR does not exhibit significant changes after RV administration.
... In most of the completed trails, 23 showed only neutral effects, confirming the bioavailability issues as a major obstacle. The only trials that led to positive effects were those in which 23 was administered at high doses (≥500 mg/day), with the best results being observed in a phase II trial on patients with type 2 diabetes and coronary heart disease [122]. In this case, treatment with 23 (500 mg/day for 4 weeks) significantly increased high-density lipoprotein levels and insulin sensitivity compared with placebo. ...
... [ [120][121][122] 24c SRT2104 [147], showing no activity against HDAC1-11, SIRT1-3, 5, and 7. 28c presents an N-methyl-3-methylmorpholine on C3 of the central benzene, which replaces the methyl carboxylate ( Figure 6D) and may be involved in more interactions, thus explaining the improved activity. 28c dose-dependently decreased H3K9, H3K18 and H3K56 acetylation levels in CRC cells and showed antiproliferative effects combined with G0/G1 arrest (Table 2). ...
... As for sirtuin activators, a great deal of work has been carried out in the development of molecules targeting SIRT1. Resveratrol (23) has been evaluated in dozens of clinical trials as a potential SIRT1a, although it mostly exhibited neutral effects and showed some benefits only at high doses because of its extremely low oral bioavailability [120][121][122]. Moreover, its polyphenolic structure, which is responsible for pleiotropic effects, represents a further issue. ...
Article
Sirtuins are NAD ⁺ -dependent protein lysine deacylase and mono-ADP ribosylases present in both prokaryotes and eukaryotes. The sirtuin family comprises seven isoforms in mammals, each possessing different subcellular localization and biological functions. Sirtuins have received increasing attention in the past two decades given their pivotal functions in a variety of biological contexts, including cytodifferentiation, transcriptional regulation, cell cycle progression, apoptosis, inflammation, metabolism, neurological and cardiovascular physiology and cancer. Consequently, modulation of sirtuin activity has been regarded as a promising therapeutic option for many pathologies. In this review, we provide an up-to-date overview of sirtuin biology and pharmacology. We examine the main features of the most relevant inhibitors and activators, analyzing their structure–activity relationships, applications in biology, and therapeutic potential.
... A total of 616 articles were retrieved through the database: 590 articles were excluded by reading titles and abstracts, and eight articles were excluded by reading the full text. Finally, 18 articles met the inclusion criteria [15][16][17][18][19][24][25][26][27][28][29][30][31][32][33][34][35][36] ( Figure 1). ree studies are by Bo et al. [16,29,30], two studies are by Imamura et al. [17], and two studies are by Abdollahi et al. [33,34], and they were merged. ...
... Six RCTs [17,18,25,31,32,35] were assessed as unclear risk of bias because of missing data and did not describe whether to use intend-to-treat analysis. e incomplete outcome data of the other RCTs are rated as low risk of bias because the number of missing people and the reasons for the missing between groups is balanced. ...
... (2) e gender composition ratio of RCTs is different. e participants in the studies of Goh et al. [25] and Brasnyó et al. [26] were all male, while the gender ratio in the study of Hoseini et al. [32] is not clear. Males and females having different sensitivities to drugs may lead to heterogeneity. ...
Article
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Background: Diabetes is a major public health concern. Resveratrol has shown great beneficial effects on hyperglycemia and insulin resistance and as an antioxidant. Methods: We searched the Chinese and English databases (such as CNKI, PubMed, and Embase) and extracted data from randomized controlled trials (RCTs). Then, RevMan 5.3 was used for bias risk assessment and meta-analysis. The primary outcome indicators include insulin-resistance-related indicators and blood-lipid-related indicators. This systematic review and meta-analysis was registered in PROSPERO (CRD42018089521). Results: Fifteen RCTs involving 896 patients were included. For insulin-resistance-related indicators, the summary results showed that, compared with the control group, homeostasis model assessment for insulin resistance (HOMA-IR) in the resveratrol group is lower (WMD: -0.99; 95% CI -1.61, -0.38; P=0.002). For blood-lipid-related indicators, the total cholesterol (TC) and triglyceride (TG) in the resveratrol group is of no statistical significance (for TC, WMD: -7.11; 95% CI -16.28, 2.06; P=0.13; for TG, WMD: -2.15; 95% CI -5.52, 1.22; P=0.21). For adverse events, the summary results showed that there was no statistical difference in the incidence of adverse events between the resveratrol and control groups (WMD: 2; 95% CI 0.44, 9.03; P=0.37). Conclusion: Based on the current evidence, resveratrol may improve insulin resistance, lower fasting blood glucose and insulin levels, and improve oxidative stress in patients with type 2 diabetes mellitus.
... e basic features of the studies were as follows: first author's name, year of publication, study site, patient age, course of disease, study sample size, resveratrol treatment dosage and intervention time, control group medication, and study design method. e eligible studies included seven studies conducted in Iran [19][20][21][22][23][24][25], three studies reported from China [26][27][28], two studies reported from India [29,30], and one study each performed in Australia [31], Egypt [32], Netherlands [33], Singapore [34], Japan [35], Spain [36], and Italy [37]. e age of the patients in the studies ranged from 40.3 to 75 years, the resveratrol dosage ranged from 8.1 to 3000 mg/day, and the observation time spanned from 1.5 weeks to 12 months (Table 1). ...
... e risk of bias in the 19 studies [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] was assessed, as presented in Figure 2. Among these studies, the risks of random sequence bias, incomplete data Figure 3). ...
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Background and aims: Previous studies on the effects of resveratrol on metabolic indicators reported contradictory findings, and these indicators have not been frequently studied in patients with type 2 diabetes. In this study, we aimed to examine the effects of resveratrol on metabolic indicators in a specific group of people with type 2 diabetes using the most recent literature. Methods: We used RevMan 5.4 and Stata 14.0 software to identify randomized controlled studies on the impact of resveratrol on metabolic indicators in patients with type 2 diabetes using relevant search terms and keywords such as "resveratrol" and "type 2 diabetes" in the China National Knowledge Infrastructure, PubMed, Cochrane, and Embase. Data were expressed as the weighted mean difference (WMD) and 95% confidence interval (CI). Results: This meta-analysis included 19 studies involving 1151 patients with type 2 diabetes, including 584 patients treated with resveratrol and 567 patients who received placebo. Compared with the control data, large doses of resveratrol (≥1000 mg) reduced fasting blood glucose levels (WMD: -18.76 mg/dL, 95% CI: -23.43, -14.09; P < 0.00001). Additionally, resveratrol reduced systolic blood pressure (WMD: -7.97 mmHg, 95% CI: -10.63, -5.31; P < 0.00001) and diastolic blood pressure (WMD: -3.55 mmHg, 95% CI: -5.18, -1.93; P < 0.00001) in patients with type 2 diabetes but did not improve waist circumference (WMD: 0.05 cm, 95% CI: -1.77, 1.88; P=0.95), triglyceride levels (WMD: -4.49 mg/dL, 95% CI: -24.23, 15.25; P=0.66), or high-density lipoprotein cholesterol levels (WMD: -1.05 mg/dL, 95% CI: -2.44, 0.33; P=0.14) in patients with type 2 diabetes. Conclusion: This systematic review and meta-analysis updated the most recent literature and provided new evidence, proving that resveratrol treatment can reduce systolic blood pressure and diastolic blood pressure. High-dose resveratrol can reduce fasting blood glucose in patients with type 2 diabetes, although it has no effect on waist circumference, triglyceride, and high-density lipoprotein cholesterol.
... Elevated levels of total cholesterol, LDL cholesterol and triglycerides and decreased levels of HDL cholesterol in the blood are characteristic of dyslipidemia and are associated with an increased risk of cardiovascular disease [32][33][34]. Previous reports on animals and humans have indicated that RES decreased levels of triacylglycerol and LDL-C and increased the levels of HDL-C in the blood [15,32,[35][36][37]. ...
... Elevated levels of total cholesterol, LDL cholesterol and triglycerides and decreased levels of HDL cholesterol in the blood are characteristic of dyslipidemia and are associated with an increased risk of cardiovascular disease [32][33][34]. Previous reports on animals and humans have indicated that RES decreased levels of triacylglycerol and LDL-C and increased the levels of HDL-C in the blood [15,32,[35][36][37]. In this study, serum triacylglycerol and LDL-C levels in the RES groups were significantly decreased versus the control group. ...
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This study investigated the effects of resveratrol (RES) supplementation on the growth performance, carcass and meat quality, blood lipid levels and ruminal bacterial microbiota of fattening goats. A total of forty castrated Nubian goats (28.25 ± 0.26 kg body weight) were randomly divided into four groups and provided with diets containing different levels of RES (0, 150, 300 and 600 mg/kg) for 120 d. The results showed that RES increased redness and intramuscular fat content, whilst reducing shear force in the longissimus dorsi muscle of goats (p < 0.05). In addition, the final weight, average daily gain, hot carcass weight, net meat weight, carcass lean percentage and eye muscle area of goats were significantly increased in the 150 mg/kg RES group compared with the other three groups, while those in the 600 mg/kg RES group significantly decreased (p < 0.05). RES significantly decreased serum triacylglycerol and LDL-C contents (p < 0.05), and increased HDL-C content and the HDL-C/TC ratio (p < 0.05). Supplementation with 150 mg/kg RES also increased the proportion of Acetitomaculum and Moryella, genera comprising short-chain fatty acid-producing bacteria. The present study indicated that an appropriate supplemental level of RES could improve the growth performance, neat percentage, meat quality, ruminal microbiota and serum lipid levels of fattening goats.
... There are some clinical trials that evaluated the effect of resveratrol supplementation on cardiovascular risk factors [18,[28][29][30]; but, their findings are inconsistent. On the other hand, the results of studies that investigated the effect of resveratrol on severity of NAFLD are not integrated [22,[31][32][33]. ...
... The study of Farzin et al. [42] found no significant effect of 12-week resveratrol supplementation (600 mg/d) on CRI-II and AIP in patients with NAFLD. However, the study of Hoseini et al. [30] reported that 500 mg/d resveratrol supplementation can improve TC/ HDL-c ratio in patients with T2DM and coronary heart disease. The study of Bo et al. [43] found that resveratrol supplementation has no lipid-modifying effect in patients with T2DM. ...
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Background Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. Methods We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. Results A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: − 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: − 0.25 ± 1.1 vs. − 0.02 ± 0.6; P = 0.47), CRI-I (mean change: − 0.25 ± 0.9 vs. − 0.09 ± 0.5; P = 0.79), CRI-II (mean change: − 0.23 ± 0.7 vs. − 0.06 ± 0.6; P = 0.38) and AC (mean change: − 0.25 ± 0.9 vs. − 0.09 ± 0.5; P = 0.79). Conclusions Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .
... Among the various naturally available bioactive molecules, polyphenols, which are secondary metabolites present in edible roots and plants, are associated with decreased risks concerning chronic, degenerative, and cardiovascular diseases when consumed regularly [5][6][7]. A large number of clinical trials have highlighted the therapeutic role of polyphenols on vascular disorders, playing a role in inherent illness-associate conditions such as inflammation, type 2 diabetes, dyslipidemia, hypertension, and oxidative stress [8][9][10][11]. Such findings have been compiled and reinforced in recent epidemiological data and metaanalysis [12][13][14][15]. ...
... Polyphenols are pleiotropic compounds that exert epigenetic, antioxidant, and anti-inflammatory effects on various tissues, including vascular and cardiac tissues [157][158][159][160]. In humans, the regular intake of polyphenols such as curcumin, catechin, quercetin, anthocyanins, and resveratrol, attenuate hypertension, hyperglycemia, hyperlipidemias, oxidative stress and overall inflammatory status, which are the major physiological conditions able to trigger cardiovascular events [8][9][10]22,160,161]. ...
Article
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Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solu-bility, chemical protection, and target achievement. Nanoencapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against car-diovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardio-vascular performance.
... It is well established that resveratrol modulates numerous components of cell signaling pathways. Furthermore, resveratrol's metabolic [77][78][79][80][81], hepatoprotective [82], neuroprotective [83], cardioprotective [84][85][86], anti-aging [82], antioxidant [87,88], anti-inflammatory [82,89], anti-diabetic [82], anti-tumor [90], cancer chemopreventive, and anti-mutagenic activities [8] have been demonstrated in recent years ( Figure 1). These beneficial properties underscore its applicability in the treatment of various diseases. ...
... The targeted manipulation of key metabolic enzymes by resveratrol could represent a useful and innovative therapeutic strategy to control tumors. Preclinical research results demonstrate the positive effects of resveratrol on cancer-associated metabolic processes [77][78][79][80][81][82][83][84][85][86][87][88][89][90]. ...
Article
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Tumor cells develop several metabolic reprogramming strategies, such as increased glucose uptake and utilization via aerobic glycolysis and fermentation of glucose to lactate; these lead to a low pH environment in which the cancer cells thrive and evade apoptosis. These characteristics of tumor cells are known as the Warburg effect. Adaptive metabolic alterations in cancer cells can be attributed to mutations in key metabolic enzymes and transcription factors. The features of the Warburg phenotype may serve as promising markers for the early detection and treatment of tumors. Besides, the glycolytic process of tumors is reversible and could represent a therapeutic target. So-called mono-target therapies are often unsafe and ineffective, and have a high prevalence of recurrence. Their success is hindered by the ability of tumor cells to simultaneously develop multiple chemoresistance pathways. Therefore, agents that modify several cellular targets, such as energy restriction to target tumor cells specifically, have therapeutic potential. Resveratrol, a natural active polyphenol found in grapes and red wine and used in many traditional medicines, is known for its ability to target multiple components of signaling pathways in tumors, leading to the suppression of cell proliferation, activation of apoptosis, and regression in tumor growth. Here, we describe current knowledge on the various mechanisms by which resveratrol modulates glucose metabolism, its potential as an imitator of caloric restriction, and its therapeutic capacity in tumors.
... It was found that phytochemical components (>10,000 components are identified) of food and medicinal plants exhibit powerful anti-radical and anti-inflammatory activity, regulate activities of α-glucosidase and lipase, reduce the level of glycaemia, improve the function of the pancreas, have a synergistic effect with hypoglycemic drugs and, thus, are highly effective in the DM treatment [103]. Thus, phytochemicals, including anthocyanins and polyphenols act as antioxidants, blocking the synthesis of prostaglandins, proinflammatory cytokines and transcription factors, in particular, NF-κB-factor [50]. Curcumin is considered suitable for the prevention and reduction of the risk of DM complications, due to its anti-inflammatory and antioxidant activity [80]. ...
... Butein, an antioxidant polyphenol, inhibits the formation of NO in vitro, protects pancreatic β-cells under conditions of excessive inflammation, and can be used to prevent the progression of DM1 [65]. Resveratrol modulates the expression of genes associated with the DM2 development by inducing the expression of several β-cell genes and insulin expression in pancreatic α-cells [50]. The effect of various components with antioxidant action on the DM course was studied under experimental conditions. ...
Article
The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the analysis of experimental and clinical studies. The sources of increased ROS generation in diabetes are specified, including the main pathways of altered glucose metabolism, oxidative damage to pancreatic β-cells, and endothelial dysfunction. The relationship between oxidative stress, carbonyl stress, and inflammation is described. The significance of oxidative stress reactions associated with hyperglycemia is considered in the context of the "metabolic memory" phenomenon. The results of our studies demonstrated significant ethnic and age-related variability of the LPO-antioxidant defense system parameters in patients with diabetes mellitus, which should be considered during complex therapy of the disease. Numerous studies of the effectiveness of antioxidants in diabetes mellitus of both types convincingly proved that antioxidants should be a part of the therapeutic process. Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery.
... However, there is a scarcity of data on the role of diet and lifestyle interventions on these biomarkers during pregnancy, and this leads to the scope of the current study. We selected a panel of antioxidant enzymes/oxidative stress markers, cofactors and adipokines based on their observed responses to dietary interventions involving polyphenols in clinical studies reported by our group, [16][17][18] as well as by others [19,20] in adults with obesity or the metabolic syndrome. ...
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Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (<20 gestation weeks) and at the end of the study period (32–26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p < 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p < 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.
... Also, J. M.O.Andrade et al. [31] showed that eight-week supplementation had a desirable effect on the expression level of the Sirt1 gene. Although, A. Hoseini et al. [32] and A. Roggero et al. [33] indicated that 500 mg supplementation of Resveratrol significantly upregulates the gene expression of Sirt. ...
Article
Background and aims Silent information regulator 1 (Sirt1) involved in histone stability, transcriptional activity, and translocation. This systematic review aimed to summarize the effects of Resveratrol on Sirt1 expression. Materials and methods Electronic databases including Scopus, Medline and web of knowledge were searched up to March 2020. Results Out of 801 studies identified in our search finally 12 articles included. Totally six studies evaluated the effects of resveratrol on SIRT1 gene expression, and six articles investigate protein expression. Conclusion The results of the included studies showed that resveratrol supplementation had beneficial effects on protein and gene expression of SIRT1.
... p < 0.001) and significantly decreasing total-/HDL-C ratio (β −0.36; 95% CI = −0.59-−0.13; p = 0.002) [108]. The effect of resveratrol on anthropometric and biochemical parameters was assessed in subjects with BMI > 30 kg/m 2 who were supplemented with 250 mg resveratrol/day, submitted physical activity and diet regulation for three months, and compared with a placebo group. ...
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Cardiovascular diseases (CVD) remain a serious public health problem and are the primary cause of death worldwide. High-density lipoprotein cholesterol (HDL-C) has been identified as one of the most important molecules in the prevention of CVD due to its multiple anti-inflammatories, anti-atherogenic, and antioxidant properties. Currently, it has been observed that maintaining healthy levels of HDL-C does not seem to be sufficient if the functionality of this particle is not adequate. Modifications in the structure and composition of HDL-C lead to a pro-inflammatory, pro-oxidant, and dysfunctional version of the molecule. Various assays have evaluated some HDL-C functions on risk populations, but they were not the main objective in some of these. Functional foods and dietary compounds such as extra virgin olive oil, nuts, whole grains, legumes, fresh fish, quercetin, curcumin, ginger, resveratrol, and other polyphenols could increase HDL functionality by improving the cholesterol efflux capacity (CEC), paraoxonase 1 (PON1), and cholesteryl ester transfer protein (CETP) activity. Nevertheless, additional rigorous research basic and applied is required in order to better understand the association between diet and HDL functionality. This will enable the development of nutritional precision management guidelines for healthy HDL to reduce cardiovascular risk in adults. The aim of the study was to increase the understanding of dietary compounds (functional foods and bioactive components) on the functionality of HDL.
... Based on DSLD data, a number of the reviewed compounds are available in OTC supplements: the alkaloid BBR; the carboxylic acid derivatives cinnamic acid and ferulic acid; the carotenoids astaxanthin and crocetin; the coumarin osthole; curcumin; the flavonoids diosmin, EGCG, naringin, quercetin, resveratrol, chrysin, and rutin; the lignan magnolol; the natural steroids withaferin A and diosgenin; and the terpenes betulinic acid and paeoniflorin. Many of these supplements exert positive physiological effects; in particular, astaxanthin and curcumin positively influence the central nervous system [100][101][102][103][104][105][106][107][108][109][110][111][112]. ...
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Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.
... Multiple potential mechanisms of RES to normalize the lipid profile in humans have already been examined. These include a decrease in mRNA expression of hepatic HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase and activation of SIRT1 [139], which may potentially lead to reverse cholesterol transport [140] and favorable alteration in lipid profile [141]. ...
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Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases.
... Hence, exploration of modern remedial procedures for combating various cancer types along with the least possible adverse effects has received consideration in recent years. Nowadays, extensive research has been conducted into anticancer characteristics of plant bioactive compounds as revolutionary therapeutic agents thanks to their low toxicity, availability as well as affordable cost [7][8][9][10]. Accordingly, one of the promising natural pharmaceutics that has received a great deal of attention is thymoquinone. ...
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Cancer is a global disease involving transformation of normal cells into tumor types via numerous mechanisms, with mortality among all generations, in spite of the breakthroughs in chemotherapy, radiotherapy and/or surgery for cancer treatment. Since one in six deaths is due to cancer, it is one of the overriding priorities of world health. Recently, bioactive natural compounds have been widely recognized due to their therapeutic effects for treatment of various chronic disorders, notably cancer. Thymoquinone (TQ), the most valuable constituent of black cumin seeds, has shown anti-cancer characteristics in a wide range of animal models. The revolutionary findings have revealed TQ's ability to regulate microRNA (miRNA) expression, offering a promising approach for cancer therapy. MiRNAs are small noncoding RNAs that modulate gene expression by means of variation in features of mRNA. MiRNAs manage several biological processes including gene expression and cellular signaling pathways. Accordingly, miRNAs can be considered as hallmarks for cancer diagnosis, prognosis and therapy. The purpose of this study was to review the various molecular mechanisms by which TQ exerts its potential as an anti-cancer agent through modulating miRNAs.
... Since ancient times, the use of natural ingredients to treat diseases such as cancer has been common and has helped scientists to discover and develop more effective drugs in this field [25,26]. Epigallocatechin gallate, curcumin, quercetin, silymarin and stilbene resveratrol are examples of plant compounds that have anti-cancer potential by regulating the cell cycle and controlling the apoptosis pathway associated with p53, or have similar performance to potent chemotherapy drugs [25,[27][28][29][30][31][32][33][34]. ...
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Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.
... Resveratrol consumption has been linked with risk factors normalization of some diseases such as colon cancer (Cai et al., 2015), type 2 diabetes (Hoseini et al., 2019), and non-alcoholic fatty liver disease (Tiao et al., 2018). Although the exact molecular mechanism underlying the beneficial effects of resveratrol is not fully understood, it is generally believed that antioxidant activity is essential to exert those health benefits (Jardim et al., 2018). ...
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The antioxidant phenotype caused by resveratrol has been recognized as a key piece in the health benefits exerted by this phytochemical in diseases related to aging. It has recently been proposed that a mitochondrial pro-oxidant mechanism could be the cause of resveratrol antioxidant properties. In this regard, the hypothesis that resveratrol impedes electron transport to complex III of the electron transport chain as its main target suggests that resveratrol could increase reactive oxygen species (ROS) generation through reverse electron transport or by the semiquinones formation. This idea also explains that cells respond to resveratrol oxidative damage, inducing their antioxidant systems. Moreover, resveratrol pro-oxidant properties could accelerate the aging process, according to the free radical theory of aging, which postulates that organisms age due to the accumulation of the harmful effects of ROS in cells. Nonetheless, there is no evidence linking the chronological lifespan (CLS) shorten occasioned by resveratrol with a pro-oxidant mechanism. Hence, this study aimed to evaluate whether resveratrol shortens the CLS of Saccharomyces cerevisiae due to a pro-oxidant activity. Herein, we provide evidence that supplementation with 100 μM of resveratrol at 5% glucose: 1) shorted the CLS of ctt1∆ and yap1∆ strains; 2) decreased ROS levels and increased the catalase activity in WT strain; 3) maintained unaffected the ROS levels and did not change the catalase activity in ctt1∆ strain; 4) lessened the exponential growth of ctt1∆ strain, which was restored with the adding of reduced glutathione. These results indicate that resveratrol decreases CLS by a pro-oxidant mechanism.
... Resveratrol supplementation did not have any effect on inflammatory markers. Four-week supplementation of resveratrol in patients with T2D and CHD had beneficial effects on glycemic control, HDL-cholesterol levels, the to-tal-/HDL-cholesterol ratio, TAC, and MDA levels [102]. In vitro and animal studies have revealed that resveratrol owns antioxidant power. ...
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Background: Diabetes is one of the most serious global public health concerns, imposing a significant burden on public health and socioeconomic development, with type 2 diabetes accounting for 90 percent of individuals with the disease (T2D). Introduction: Beyond the hereditary factor, there are several risk factors associated with the development of this syndrome; the lifestyle plays an increasingly predominant role in the development of the metabolic complications related to T2D and a significant role in the onset of this syndrome is played by an unbalanced diet. Polyphenolic food is a plant-based food, including vegetables, fruits, whole grains, tea, coffee, and nuts. In recent years, there has been growing evidence that polyphenols, due to their biological properties, may be used as nutraceuticals and supplementary treatments for various aspects of T2D. Polyphenols may influence glycemia and T2D through hypoglycemic properties, such as reduced insulin resistance, reduced fasting blood glucose, and glycosylated hemoglobin value. Based on several in vitro, animal models, and some human studies, it has been detected that polyphenol-rich products modulate carbohydrate and li-pid metabolism, attenuate hyperglycemia, dyslipidemia, and insulin resistance, improve adipose tissue metabolism, and alleviate oxidative stress and stress-sensitive signaling pathways and inflammatory processes. Methods: This manuscript summarizes human clinical trials conducted within the last 5 years linking dietary polyphenols to T2D, with a focus on polyphenolic foods found in the Mediterra-nean diet. Results: Intaking polyphenols and their food sources have demonstrated beneficial effects on insulin resistance and other cardiometabolic risk factors. Prospective studies have shown inverse associations between polyphenol intake and T2D. The Mediterranean diet and its key components , olive oil, nuts, and red wine, have been inversely associated with insulin resistance and T2D. Conclusion: In conclusion, the intake of polyphenols may be beneficial for both insulin resistance and T2D risk. However, other human clinical studies are needed to evaluate the suitable dose and duration of supplementation with polyphenolic food in T2D patients.
... Several studies have shown that metabolic and genetic disorders there are in patients with diabetes and cancer [14][15][16]. In addition, circRNAs can exert modulatory effects on cancer-related processes, such as tumorigenesis, tumor progression, and apoptosis [17,18]. ...
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Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogene-ity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM.
... Several studies have shown that metabolic and genetic disorders there are in patients with diabetes and cancer [14][15][16]. In addition, circRNAs can exert modulatory effects on cancer-related processes, such as tumorigenesis, tumor progression, and apoptosis [17,18]. ...
Article
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Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM.
... On the other hand, a cross-sectional study revealed that higher intakes of fruits and vegetables are associated with levels of oxidative stress and inflammation as the main contributors of the pathogenesis of depression [51]. In addition, some studies have demonstrated that phytochemicals can improve oxidative stress [52,53] and inflammation [54][55][56]. Phytochemicals can suppress fatty acid synthesis and gluconeogenesis, increase mitochondrial oxidation, reduce the levels of oxidant agents as well as free radicals, and attenuate the activity of inflammatory markers [22-24, 57, 58]. There was no significant relationship between DPI score and QoL after adjusting for all confounding factors (Model III). ...
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Background There is increasing evidence that the dietary intake of phytochemicals is inversely associated with severity of depression and positively associated with quality of life (QoL). The present study investigated the relationship between dietary phytochemical index (DPI) with depression and QoL scores in Iranian adolescent girls. Methods A total of 733 adolescent girls from Mashhad and Sabzevar cities in northeastern Iran were entered into this cross-sectional study. Assessment of depression and QoL was performed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaire, respectively. Assessment of dietary intake was undertaken by a qualified dietitian, using a validated food-frequency questionnaire (FFQ) containing 168 food items. To explore the association between DPI with QoL and depression, logistic regression was used in crude and adjusted models. Results The participants in the fourth quartile of DPI compared with the first quartile had a 50% lower odds of depression (OR: 0.50; 95% CI: 0.30-0.84, P = 0.009) This relation remained significant in all adjusted models. The adolescents in highest quartile of DPI compared with the first quartile had 38% lower odds of poor QoL (OR: 0.62; 95% CI: 0.41-0.94, P = 0.02). This association remained significant in adjusted models I and II, but not after adjusting for all confounding variables (OR: 0.67; 95% CI: 0.43-1.02, P = 0.06) (Model III). Conclusions DPI was inversely associated with risk of depression. The association between DPI score and QoL remained unclear. Further prospective and interventional studies are required.
... Moreover, diabetes is associated with numerous complications [4]. Results of human studies and clinical trials indicate that resveratrol therapy markedly reduces blood glucose levels and improves insulin action in patients with type 2 diabetes [9][10][11][12][13][14]. Moreover, it was shown that resveratrol alleviates the inflammatory and oxidative stress in people with type 2 diabetes [2,10]. ...
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Resveratrol is a biologically active diphenolic compound exerting multiple beneficial effects in the organism, including anti-diabetic properties. This action is, however, not fully elucidated. In the present study, we examined effects of resveratrol on some parameters related to insulin signaling, and also on diabetes-associated dysregulation in Goto-Kakizaki (GK) rats with congenital type 2 diabetes. Resveratrol was given at the dose of 20 mg/kg b.w. for 10 weeks. It was shown that the expression and phosphorylation levels of insulin receptor in the skeletal muscle of GK rats were significantly decreased, compared with control animals. However, these changes were totally prevented by resveratrol. Liver expression of the insulin receptor was also reduced, but in this case, resveratrol was ineffective. Resveratrol was also demonstrated to significantly influence parameters of insulin binding (dissociation constant and binding capacity) in the skeletal muscle and liver. Moreover, it was shown that the expression levels of proteins related to intracellular glucose transport (GLUT4 and TUG) in adipose tissue of GK rats were significantly decreased. However, treatment with resveratrol completely abolished these changes. Resveratrol was found to induce normalization of TUG expression in the skeletal muscle. Blood levels of insulin and GIP were elevated, whereas proinsulin and GLP-1 diminished in GK rats. However, concentrations of these hormones were not affected by resveratrol. These results indicate that resveratrol partially ameliorates diabetes-associated dysregulation in GK rats. The most relevant finding covers the normalization of the insulin receptor expression in the skeletal muscle and also GLUT4 and TUG in adipose tissue.
... However, resveratrol administration for 6 months did not have beneficial metabolic effects in human patients with T2D (Bo et al., 2016). In contrast, small but significant effects of resveratrol on blood glucose, lipid profile or bone mineral density of patients with T2D have recently been reported (Bo et al., 2018;Hoseini et al., 2019). ...
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Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organism in vivo , dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.
... Table 1 reports some of the main effects exerted by phenolic compound-based nutraceuticals in both diabetic animal models and patients. Decreased fasting blood glucose, HbA1c, increased insulin, improved hepatic glycogen content, increased glycogen synthase activity and reduced glycogen phosphorylase activity Streptozotocin-nicotinamide diabetic rats 5 mg/kg body weight; 30 days [110] Alleviated diabetic nephropathy by reduced renal dysfunction and oxidative stress Streptozotocin-induced diabetic rats 5 or 10 mg/kg body weight; 2 weeks [111] Ameliorated cognitive decline by inhibition of hippocampal apoptosis via the Bcl-2/Bax and caspase-3 pathway, improvement of synaptic dysfunction Streptozotocin-induced diabetic rats 80 mg/kg body weight; 4 weeks [112] Enhanced cerebral vasodilator function, improved cognitive performance Patients with T2D a single dose of 75 mg [113] Reduced fasting blood glucose, increased serum HDL-cholesterol levels, decreased total-/HDL-cholesterol ratio, increased total antioxidant capacity, decreased plasma MDA levels, upregulation of PPAR-γ and SIRT1 in PBMCs Subjects with T2D and coronary heart disease 500 mg/day; 4 weeks [114] Reduced foot ulcer size and plasma fibrinogen level Patients with diabetic foot syndrome 50 mg/ twice a day; 60 days [115] Phenolic acids Curcumin (Hydroxycinnamic acid) Improved diabetes-induced endothelial dysfunction through superoxide reduction and PKC inhibition Streptozotocin-induced diabetic rats 30 and 300 mg/kg body weight; 6 weeks [116] Reduced fasting blood glucose, reduced weight and BMI Overweight patients with T2D 1500 mg/3 times in a day; 10 weeks [117] Ferulic acid (Hydroxycinnamic acid) ...
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Research in pharmacological therapy has led to the availability of many antidiabetic agents. New recommendations for precision medicine and particularly precision nutrition may greatly contribute to the control and especially to the prevention of diabetes. This scenario greatly encourages the search for novel non-pharmaceutical molecules. In line with this, the daily and long-term consumption of diets rich in phenolic compounds, together with a healthy lifestyle, may have a protective role against the development of type 2 diabetes. In the framework of the described studies, there is clear evidence that the bio accessibility, bioavailability, and the gut microbiota are indeed affected by: the way phenolic compounds are consumed (acutely or chronically; as pure compounds, extracts, or in-side a whole meal) and the amount and the type of phenolic compounds (ex-tractable or non-extractable/macromolecular antioxidants, including non-bioavailable polyphenols and plant matrix complexed structures). In this review, we report possible effects of important, commonly consumed, phenolic-based nutraceuticals in pre-clinical and clinical diabetes studies. We highlight their mechanisms of action and their potential effects in health promotion. Translation of this nutraceutical-based approach still requires more and larger clinical trials for better elucidation of the mechanism of action toward clinical applications.
... Recently, convincing evidence has demonstrated that components isolated from natural plant products have a wide range of biological effects, including antioxidant, antiinflammatory, and anticancer properties [16][17][18]. Thymoquinone (C 10 H 12 O 2 ; TQ) is a volatile oil ingredient derived from Nigella sativa Linn. seeds. ...
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Despite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa , has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.
... Although their molecular structures differ, the presence of flavonoids significantly increases the bioavailability of other compounds (Böhm 1994;Gu et al., 2004;Ding et al., 2016). Many studies have emphasized the beneficial effects of flavonoids in the daily diet and suggested that the consumption of flavonoids could be effective in reducing the risk of chronic heart and brain disorders and cancer (Kozłowska and Szostak-Wegierek 2014;Panche et al., 2016;Honari et al., 2019;Hoseini et al., 2019;Maleki Dana et al., 2021). One prominent member of the flavonoid family is quercetin (3,3′,4′,5,7-pentahydroxyflavone), which is present in different kinds of fruits and vegetables, such as buckwheat, broccoli, and onions. ...
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Many cellular signaling pathways contribute to the regulation of cell proliferation, division, motility, and apoptosis. Deregulation of these pathways contributes to tumor cell initiation and tumor progression. Lately, significant attention has been focused on the use of natural products as a promising strategy in cancer treatment. Quercetin is a natural flavonol compound widely present in commonly consumed foods. Quercetin has shown significant inhibitory effects on tumor progression via various mechanisms of action. These include stimulating cell cycle arrest or/and apoptosis as well as its antioxidant properties. Herein, we summarize the therapeutic effects of quercetin in gastrointestinal cancers (pancreatic, gastric, colorectal, esophageal, hepatocellular, and oral).
... Numerous preclinical and clinical studies have confirmed the efficacy of this phytoalexin in the treatment of diabetes [30][31][32], neurodegenerative diseases [34,35], cancer [36][37][38], aging [39], obesity [40,41], cardiovascular disease [42,43], and regeneration of bone tissues [44]. Resveratrol, as a compound of natural origin with proven anti-inflammatory and antimicrobial activity, seems to be an alternative to synthetic drugs used in vaginal therapy, especially with the observed spread of antimicrobial resistance, mainly in Neisseria gonorrhoeae [45]. ...
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In recent years, polyphenols have been extensively studied due to their antioxidant, anticancer, and anti-inflammatory properties. It has been shown that anthocyanins, flavonols, and flavan-3-ols play an important role in the prevention of bacterial infections, as well as vascular or skin diseases. Particularly, resveratrol, as a multi-potent agent, may prevent or mitigate the effects of oxidative stress. As the largest organ of the human body, skin is an extremely desirable target for the possible delivery of active substances. The transdermal route of administration of active compounds shows many advantages, including avoidance of gastrointestinal irritation and the first-pass effect. Moreover, it is non-invasive and can be self-administered. However, this delivery is limited, mainly due to the need to overpassing the stratum corneum, the possible decomposition of the substances in contact with the skin surface or in the deeper layers thereof. In addition, using resveratrol for topical and transdermal delivery faces the problems of its low solubility and poor stability. To overcome this, novel systems of delivery are being developed for the effective transport of resveratrol across the skin. Carriers in the micro and nano size were demonstrated to be more efficient for safe and faster topical and transdermal delivery of active substances. The present review aimed to discuss the role of resveratrol in the treatment of skin abnormalities with a special emphasis on technologies enhancing transdermal delivery of resveratrol.
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Resveratrol and quercetin are natural compounds contained in many foods and beverages. Reports indicate implications for the health of the general population; on the other hand the use of both compounds has interesting results for the treatment of many diseases as cardiovascular affections, diabetes, Alzheimer’s disease, viral and bacterial infections among others. Based on their capacities described as anti-inflammatory, antioxidant, and anti-aging, resveratrol and quercetin showed antiproliferative and anticancer activity specifically in maligned cells. These molecular characteristics trigger the pharmacological repurposing of both compounds and improved its research for treating different cancer types with interesting results at in vitro, in vivo, and clinical trial studies. Meanwhile, the development of different systems of drug release in specific sites as nanomaterials and specifically the nanoparticles, potentiates the personal treatment perspective in conjunct with the actual cancer therapies; regularly invasive and aggressive, the perspective of nanomedicine as higher effective and lower invasive has gained popularity. Knowledge of molecular interactions of resveratrol and quercetin in diseases confirms the evidence of multiple benefits, while the multiple analyses suggested a positive response for the treatment and diagnostics of cancer in different stages, including at metastatic stage. The present work reviews the reports related to the impact of resveratrol and quercetin in cancer treatment and its effects when the antioxidants are encapsulated in different nanoparticle systems, which improve the prospects of cancer treatment.
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Diabetic cardiomyopathy is the leading cause of death among people with diabetes. Despite its severity and poor prognosis, there are currently no approved specific drugs to prevent or even treat diabetic cardiomyopathy. There is a need to understand the pathogenic mechanisms underlying the development of diabetic cardiomyopathy to design new therapeutic strategies. These mechanisms are complex and intricate and include metabolic dysregulation, inflammation, oxidative stress, fibrosis, and apoptosis. Sirtuins, a group of deacetylase enzymes, play an important role in all these processes and are, therefore, potential molecular targets for treating this disease. In this review, we discuss the role of sirtuins in the heart, focusing on their contribution to the pathogenesis of diabetic cardiomyopathy and how their modulation could be therapeutically useful.
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Obesity is a common nutritional disorder, associated with a variety of chronic diseases, among them, type 2 diabetes (T2DM) has emerged as a serious worldwide health problem. Insulin resistance and β cell dysfunction are the main pathological characteristics of T2DM, and obesity and hyperlipidemia are the critical causal factors. It is commonly accepted that dietary factors are of paramount importance in the management of obesity and T2DM. Particularly, many botanic products and their extracts are endowed with a wide spectrum of biological activities, making them extensively studied as anti-obesity and anti-diabetes dietary supplements or new drug candidates. In this review, we aimed to summarize the effects, related mechanisms, and safety issues of dietary continents on obesity and T2DM, to provide theoretical support for better research and development of dietary therapy strategy for the treatment of obesity and T2DM. Based on a bunch of clinical investigations, specific carbohydrates and fatty acids, such as dietary fibers, polysaccharides, unsaturated fatty acids, have hypoglycemic and hypolipidemic effects. Vitamin D plays important role in metabolism and immunity modulation. Apart from them, natural bioactive ingredients from plants, such as flavonoids, polyphenols, alkaloids, terpenoids, polysaccharides, and quinones are efficient in helping weight loss and improving insulin sensitivity and glycemic control. They can protect β cell function by anti-inflammation, anti-oxidation, and anti-apoptosis properties, as well as regulating lipid metabolism. Therefore, promoting the consumption of diverse natural bioactive ingredients-rich products could be an effective nutritional strategy to benefit patients with obesity and type 2 diabetes.
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Natural products and synthetic analogs have drawn much attention as potential therapeutical drugs to treat metabolic syndrome. We reviewed the underlying mechanisms of 32 natural products and analogs with potential pharmacological effects in vitro, and especially in rodent models and/or patients, that usually act on the PPAR pathway, along with other molecular targets. Recent outstanding total syntheses or semisyntheses of these lead compounds are stated. In general, they can activate the transcriptional activity of PPARα, PPARγ, PPARα/γ, PPARβ/δ, PPARα/δ, PPARγ/δ and panPPAR as weak, partial agonists or selective PPARγ modulators (SPPARγM), which may be useful for managing obesity, type 2 diabetes (T2D), dyslipidemia and non-fatty liver disease (NAFLD). Terpenoids is the largest group of compounds that act as potential modulators on PPARs and are comprised from small lipophilic cannabinoids to lipophilic pentacyclic triterpenes and polar saponins. Shikimates-phenylpropanoids include polar heterocyclic flavonoids and phenolic compounds containing at least one C3-C6 unit and usually a double bond on the propyl chain. Quercetin (19), resveratrol (24) and curcumin (27), stand out from this group for exhibiting beneficial effects on patients. Alkaloids, the minor group of potential modulators on PPARs, include berberine (30), which has been widely explored in preclinical and clinical studies for its potential beneficial effects on T2D and dyslipidemia. However, large-scale clinical trials may be warranted for the promising compounds.
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Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.
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As one of the most common complications of diabetes, nephropathy develops in approximately 40% of diabetic individuals. Although end stage kidney disease is known as one of the most consequences of diabetic nephropathy, the majority of diabetic individuals might die from cardiovascular diseases and infections before renal replacement treatment. Moreover, the routine medical treatments for diabetes hold undesirable side effects. The explosive prevalence of diabetes urges clinicians and scientists to investigate the complementary or alternative therapies. Phytochemicals are emerging as alternatives with a wide range of therapeutic effects on various pathologies, including diabetic kidney disease. Of those phytochemicals, resveratrol, a natural polyphenolic stilbene, has been found to exert a broad spectrum of health benefits via various signaling molecules. In particular, resveratrol has gained a great deal of attention because of its anti-oxidative, anti-inflammatory, anti-diabetic, anti-obesity, cardiovascular-protective, and anti-tumor properties. In the renal system, emerging evidence shows that resveratrol has already been used to ameliorate chronic or acute kidney injury. This review critically summarizes the current findings and molecular mechanisms of resveratrol in diabetic renal damage. In addition, we will discuss the adverse and inconsistent effects of resveratrol in diabetic nephropathy. Although there is increasing evidence that resveratrol affords great potential in diabetic nephropathy therapy, these results should be treated with caution before its clinical translation. In addition, the unfavorable pharmacokinetics and/or pharmacodynamics profiles, such as poor bioavailability, may limit its extensive clinical applications. It is clear that further research is needed to unravel these limitations and improve its efficacy against diabetic nephropathy. Increasing investigation of resveratrol in diabetic kidney disease will not only help us better understand its pharmacological actions, but also provide novel potential targets for therapeutic intervention.
Article
This study aimed to review the literature on studies that evaluated resveratrol's effects supplementation on parameters of diabetes in humans. We conducted an online search in the following databases: Pubmed, Lilacs, Scielo, Scopus, Web of Science, Embase, and Cochrane. It included experimental studies that investigated the effects of resveratrol supplementation for diabetes treatment or prevention and its relationship with fasting blood glucose, insulin resistance, and glycated hemoglobin. Observational, non-human studies and non-randomized clinical trials were excluded. We conducted a meta-analysis to evaluate the effects of resveratrol supplementation on fasting blood glucose, insulin resistance, and glycated hemoglobin. Thirty studies were included in the review. Almost 60% demonstrated at least one significant effect of the resveratrol supplementation related to diabetes. In the meta-analysis, there was a significant effect on the reduction of insulin resistance [SMD: −0.34; CI 95%: −0.64, −0.04; p = 0.01; I² = 70%] and glycated hemoglobin [SMD: −0.64; CI 95%: −1.22, −0.07; p = 0.01; I² = 90%]. For fasting blood glucose, the results were significant only for individuals with diabetes [SMD: −0.85; CI 95%: −1.49, −0.21; p = 0.01; I² = 90%]. This systematic review with meta-analysis demonstrated that resveratrol supplementation has protective effects on diabetes parameters.
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The human sirtuins are a group of NAD-dependent protein deacylases. They “erase” acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as “successful” examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials.
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We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = −0.40 mg/L; 95% CI: −0.70 to −0.09 mg/L; p = .01) and CRP (MWD = −0.31 mg/L; 95% CI: −0.47 to −0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = −0.48 mg/L; 95% CI: −0.92 to −0.04 mg/L; p = .03) and CRP (WMD = −0.47 mg/L, 95% CI = −0.69 to −0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.
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Resveratrol, a naturally occurring stilbene, is the subject of intense research due to its numerous pharmacological effects. The most common form of resveratrol is trans-isomer, but it can also exist in cis-form, and as glucoside (piceid) and oligomer. Resveratrol is widely spread among different plant species, with Arachis hypogea, Vitis vinifera, and Polygonum cuspidatum being the richest sources of this compound. Wine is recognized as one of the main sources of resveratrol in the human diet and wine by-products are considered as a cost-effective material for its extraction. Resveratrol is extensively metabolized into sulfate and glucuronide conjugates and its final bioavailability is influenced by different factors including gut microbiota composition and diet. Due to the complex mechanism of action, resveratrol can exhibit various health benefits related to antiinflammatory, antiplatelet, and antitumor activities.
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Previous studies have suggested the beneficial effects of resveratrol against cardiovascular disease (CVD). However, there are inconsistent results on cardiovascular-related biomarkers mainly because of variable dosage, intervention time and baseline characteristics of the population. Thus, the exact effect of resveratrol remains unclear. We conducted a review to classify the studies that applied resveratrol to supplement humans according to the major biomarkers and identify which protocol characteristics would be associated with each result profile. Randomized clinical trials that assessed resveratrol effect on biomarkers related to atherosclerosis were searched in databases. Biochemical data were collected from 27 studies on the baseline and post-intervention time. We selected 12 biomarkers to compose the matrix, based on their clinical relevance and higher variation level. A total of 32 assays were obtained from these 27 studies. The net change (%) was calculated for each biomarker. Applying multivariate analysis, the assays were grouped into 3 clusters. Studies that composed Cluster II were characterized by a mean dose of 454.14 mg/day for 74.21 days and showed higher reduction of triglyceride concentration and blood pressure, while those composing Cluster III applied doses around 273.75 mg/day for about 175.33 days and showed the highest HDL increase. Thus, interventions with resveratrol could be customized according to the patient condition, in terms of “dose/time of intervention”. This information can be applied to combine resveratrol with drugs to reduce blood pressure or improve lipid profile in further clinical studies.
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Diabetes mellitus (DM) is a chronic degenerative disease that affects more than 450 million people in the world, with type 2 being the most prevalent. Type 2 diabetes mellitus (T2DM) is characterized by resistance to insulin, a hormone that is involved in glucose homeostasis. There are medications that prevent and control hyperglycemia, however, the continuous and long-term intake of some of these medications cause side effects on health. As an adjunct to treatment with synthetic drugs, the use of natural extracts with antidiabetic properties has been proposed as a complement to comprehensive treatment for the control of DM. The objective of this chapter is to show the general panorama of DM, the conditions associated with its development, and present some phytochemicals with the ability to intervene in a beneficial way of glucose metabolism. As a result of the research, natural compounds with antidiabetic action mechanisms such as inhibition of α-amylase and α-glucosidase enzymes were listed. In conclusion, the use of natural extracts with hypoglycemic characteristics works as a complementary treatment to control blood glucose levels in T2DM. However, more research is needed on the effect of phytochemicals on health that helps in the treatment of this disease.
Article
Background Type 2 diabetes mellitus (T2DM) is a progressive meta-inflammatory disorder, which induce micro and macrovascular complications. Resveratrol is a nutraceutical known to have antioxidant and anti-inflammatory properties. It improves insulin resistance; however, no clear evidence regarding its effects in patients with T2DM. Objectives We aimed to evaluate the efficacy and the safety of oral resveratrol supplementation in type 2 diabetic patients concerning dose and duration. Methods We searched PubMed, Cochrane Library, Scopus, WOS, Wiley, and Google Scholar for RCTs evaluating the efficacy and safety of resveratrol on patients with T2DM. We screened the studies for the eligibility criteria, performed the quality assessment, extracted the studies’ characteristics, baseline, and outcome data of interest, and finally conducted the meta-analysis using RevManV5.3. Results This systematic review and meta-analysis, including 17 RCTs with total 871 patients with T2DM, showed that resveratrol was superior to placebo on fasting blood glucose (FBG) and total cholesterol (TC) with doses ≥500 mg {MD = −13.34, 95%CI [−22.73, −3.95], P = 0.005}, {MD = −5.64, 95%CI [−6.95, −4.33], P < 0.00001} respectively. Moreover, it improved HbA1c at three months {MD = −0.41, 95%CI [−0.65, −0.16], P = 0.001 and systolic blood pressure {MD: −7.91, 95%CI [−10.44, −5.37], P < 0.00001}. Conclusion We concluded that resveratrol beneficially modulates glycemic control as well as cardiometabolic parameters in patients with T2DM.
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Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM.
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Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, and previous studies have shown that lipid deposits in the kidneys can lead to diabetic kidney damage. Resveratrol reduces circulating glucose and lipid concentrations, but it is unknown whether it can reduce renal lipid deposition and lipotoxic damage by regulating local lipid metabolism. We first showed that abnormal lipid metabolism is closely related to DKD in patients. There were excessive lipid deposits in the kidneys of patients with various stages of DKD, alongside abnormal expression of the junctional adhesion molecule-like (JAML)/sirtuin 1 (Sirt1) lipid synthesis pathway (P < 0.05). Next, we fed C57BL/6J mice a high-fat diet for 12 weeks, which caused an increase in body mass, blood glucose concentration, and blood lipid concentrations; and abnormalities in renal function (P < 0.05). Resveratrol administration ameliorated the defects in circulating lipid and glucose concentrations, renal dysfunction, the renal expression of components of the JAML/Sirt1 lipid synthesis pathway, and the expression of the adipose differentiation-related protein in the mice (P < 0.05). Histological staining also showed less lipid deposition and kidney damage. Thus, resveratrol regulates the JAML/Sirt1 lipid synthesis pathway, reduces lipid deposition in the kidney, and ameliorates diabetic kidney damage.
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Type 2 diabetes mellitus (T2DM) and heart failure (HF) are diseases characterized by high morbidity and mortality. They often occur simultaneously and increase the risk of each other. T2DM complicated with HF, as one of the most dangerous disease combinations in modern medicine, is more common in middle-aged and elderly people, making the treatment more difficult. At present, the combination of blood glucose control and anti-heart failure is a common therapy for patients with T2DM complicated with HF, but their effect is not ideal, and many hypoglycemic drugs have the risk of heart failure. Abnormal insulin signaling pathway, as a common pathogenic mechanism in T2DM and HF, could lead to pathological features such as insulin resistance (IR), myocardial energy metabolism disorders, and vascular endothelial disorders. The therapy based on the insulin signaling pathway may become a specific therapeutic target for T2DM patients with HF. Here, we reviewed the mechanisms and potential drugs of insulin signaling pathway in the treatment of T2DM complicated with HF, with a view to opening up a new perspective for the treatment of T2DM patients with HF and the research and development of new drugs.
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Background Lipids are ubiquitous metabolites with diverse functions. Excessive lipid accumulation can trigger lipid redistribution among metabolic organs such as adipose, liver and muscle, thus altering the lipid metabolism. It has been revealed that disturbed lipid metabolism would cause multiple disease complications and is highly correlated with human morbidity. Resveratrol (RSV), a phytoestrogen with antioxidant, can modulate insulin resistance and lipid profile. Recently, research on RSV supplementation to improve glucose and lipid metabolism has been controversial. A meta-analysis may provide a scientific reference for the relationship between lipid metabolism and RSV supplementation. Methods and Analysis We searched the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to October 2021 using relevant keywords. A comprehensive search for randomized controlled trials (RCTs) was performed. For calculating pooled effects, continuous data were pooled by mean difference (MD) and 95% confidence interval (CI). Adopting the method of inverse-variance with a random-effect, all related statistical analyses were performed using the Rev Man V.5.3 and STATA V.15 software. Results A total of 25 articles were incorporated into the final meta-analysis after removal of duplicates by checking titles and abstracts and excluding non-relevant articles. The selected articles had a total of 1,171 participants, including 578 in the placebo group and 593 in the intervention group. According to the current meta-analysis, which demonstrated that there was a significant decrease in waist circumference (SMD = –0.36; 95% CI: –0.59, –0.14; P = 0.002; I ² = 88%), hemoglobin A1c (–0.48; –0.69, –0.27; P ≤ 0.001; I ² = 94%), total cholesterol (–0.15; –0.3, –0.01; P = 0.003; I ² = 94%), low density lipoprotein cholesterol (–0.42; –0.57, –0.27; P ≤ 0.001; I ² = 92%), high density lipoprotein cholesterol (0.16; –0.31, –0.02; P = 0.03; I ² = 81%) following resveratrol administration. Conclusion These results suggest that RSV has a dramatic impact on regulating lipid and glucose metabolism, and the major clinical value of resveratrol intake is for obese and diabetic patients. We hope that this study could provide more options for clinicians using RSV. Furthermore, in the future, large-scale and well-designed trials will be warranted to confirm these results. Systematic Review Registration Website [ https://www.crd.york.ac.uk/prospero/#recordDetails ], identifier [CRD42021244904].
Article
Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5,000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.
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The abuse of alcoholic beverages has been associated with an increased risk of chronic-degenerative diseases, including diabetes mellitus, so that there is a general diffidence towards the low/moderate consumption of wine by individuals with type-2 diabetes (T2D) or at risk of developing it. This narrative review investigates by critical revision of the scientific literature whether wine/grape derivatives must be excluded or if their low/moderate consumption could be part of the daily diet of T2D individuals. Although further intervention studies on the consumption of alcoholic beverages and the development or control of T2D are needed, the burden of evidence suggests that low/moderate wine consumption could have beneficial effects.
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Background Long-term high-intensity exercise can lead to reproductive endocrine and spermatogenic dysfunction. This research is to investigate the effect of resveratrol on the reduction of reproductive dysfunction induced by high-intensity exercise, and to screen relevant factors and signal transduction pathways. Methods Rats were randomly divided into three groups, a control group, an intensive exercise group (IE group), and a resveratrol-treated group (RSV group). After 9 weeks of exercise, the sperm density and reproductive hormone concentrations were measured, along with antioxidation, inflammatory cytokine production, and histological analyses performed for each group. In addition, a proteomics analysis of the IE group and RSV group were conducted. Results We found that compared with the control group, the average sperm density (P < 0.05) and testosterone concentration (P < 0.05) in the IE group decreased significantly. Additionally, in testis tissue the concentration of the inflammatory cytokines IL-6 (P < 0.01) and TNF-α (P < 0.01) increased significantly. Also, a significant decrease in superoxide dismutase (SOD) activity (P < 0.01) and a significant increase in the malondialdehyde (MDA) concentration (P < 0.01) were noted. In the RSV group, the average sperm density (P < 0.01), testosterone (P < 0.01) and follicle stimulating hormone (FSH) levels (P < 0.01) all increased in comparison to the IE group, and the concentration of IL-6 (P < 0.01) and TNF-α (P < 0.01) were found to be significantly decreased. Compared with the IE group, the SOD activity in the RSV group was significantly increased (P < 0.01), while the MDA content decreased (P < 0.01). Furthermore, histological analysis showed that the number of spermatogenic epithelial cells in the RSV group was higher than that of the IE group. There were a number of spermatogenic regulatory proteins identified in the proteomics analysis, including Clusterin, Piwi like homolog 1 (Piwil1), Zona pellucida binding protein (Zpbp), Heat shock-related 70 kDa protein 2 (Hspa2), Centrin 1, and Bardet-Biedl syndrome 2 protein (Bbs2). It was found that the proteins that differed between the two groups were mainly involved in pathways such as complement and coagulation cascades, the extracellular matrix-receptor interactions, etc. Conclusions The present study demonstrates that after high-intensity exercise, the inflammatory cascade in the tissue of the testis increases with decreased resistance to oxidation and disordered spermatogenic function. Resveratrol can improve the reproductive dysfunction of rats that was induced by high-intensity exercise. It mostly promotes reproductive function by increasing testosterone secretion, reducing the inflammatory response, improving the antioxidant capacity, affecting the expression of spermatogenic regulatory proteins, and enhancing the signal transduction pathway of spermatogenesis.
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Resveratrol increases the production of nitric oxide (NO) in endothelial cells by upregulating the expression of endothelial NO synthase (eNOS), stimulating eNOS enzymatic activity, and preventing eNOS uncoupling. At the same time, resveratrol inhibits the synthesis of endothelin-1 and reduces oxidative stress in both endothelial cells and smooth muscle cells. Pathological stimuli-induced smooth muscle cell proliferation, vascular remodeling, and arterial stiffness can be ameliorated by resveratrol as well. In addition, resveratrol also modulates immune cell function, inhibition of immune cell infiltration into the vascular wall, and improves the function of perivascular adipose tissue. All these mechanisms contribute to the protective effects of resveratrol on vascular function and blood pressure in vivo. Sirtuin 1, AMP-activated protein kinase, and estrogen receptors represent the major molecules mediating the vascular effects of resveratrol.
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Resveratrol is the most well-known polyphenolic stilbenoid, present in grapes, mulberries, peanuts, rhubarb, and in several other plants. Resveratrol can play a beneficial role in the prevention and in the progression of chronic diseases related to inflammation such as diabetes, obesity, cardiovascular diseases, neurodegeneration, and cancers among other conditions. Moreover, resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. At the molecular level, it targets sirtuin, adenosine monophosphate kinase, nuclear factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis. Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes’ expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties. The effects of this biologically active compound on the immune system are associated with widespread health benefits for different autoimmune and chronic inflammatory diseases. This review offers a systematic understanding of how resveratrol targets multiple inflammatory components and exerts immune-regulatory effects on immune cells.
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The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro and in vivo, have highlighted the protective bone aptitude of RSV both as promoter of osteoblasts’ proliferation and antagonist of osteoclasts’ differentiation, they could be interesting in view of applications in the field of dentistry and maxillofacial surgery. This review has brought together experimental findings on the use of RSV in the regeneration of bone tissue comprising also its application associated with scaffolds and non-transfusional hemocomponents.
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Abstract The incidence and prevalence of diabetes mellitus is rapidly increasing worldwide at an alarming rate. Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, accounting for approximately 90–95% of the total diabetes cases worldwide. Besides affecting the ability of body to use glucose, it is associated with micro-vascular and macro-vascular complications. Augmented atherosclerosis is documented to be the key factor leading to vascular complications in T2DM patients. The metabolic milieu of T2DM, including insulin resistance, hyperglycemia and release of excess free fatty acids, along with other metabolic abnormalities affects vascular wall by a series of events including endothelial dysfunction, platelet hyperactivity, oxidative stress and low-grade inflammation. Activation of these events further enhances vasoconstriction and promotes thrombus formation, ultimately resulting in the development of atherosclerosis. All these evidences are supported by the clinical trials reporting the importance of endothelial dysfunction and platelet hyperactivity in the pathogenesis of atherosclerotic vascular complications. In this review, an attempt has been made to comprehensively compile updated information available in context of endothelial and platelet dysfunction in T2DM.
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Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA). Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD.
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Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Resveratrol (trans-3,5,4-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties. The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α). Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group. The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS). The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured. The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis. After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen. Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression. Resveratrol treatment decreased serum levels of IL-6 and IL-8. Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response. The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways. Thus resveratrol might be a therapeutic modality in COPD.
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Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM). In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured. Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m², P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5. In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings.
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Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD⁺-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging researches, it is well known that Sir2 is a positive regulator of replicative lifespan and, in this context, the RSV effects have been already examined. Here, we analyzed RSV effects during chronological aging, in which Sir2 acts as a negative regulator of chronological lifespan (CLS). Chronological aging refers to quiescent cells in stationary phase; these cells display a survival-based metabolism characterized by an increase in oxidative stress. We found that RSV supplementation at the onset of chronological aging, namely at the diauxic shift, increases oxidative stress and significantly reduces CLS. CLS reduction is dependent on Sir2 presence both in expired medium and in extreme Calorie Restriction. In addition, all data point to an enhancement of Sir2 activity, in particular Sir2-mediated deacetylation of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount of the acetylated active form of Pck1, whose enzymatic activity is essential for gluconeogenesis and CLS extension.
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Physical inactivity reduces, and exercise training increases, mitochondrial capacity. In rodents, exercise training effects can be augmented by large doses of resveratrol supplementation but whether this can occur in humans with a smaller dose is unclear. This study sought to determine the effects of resveratrol supplementation in combination with exercise training on skeletal muscle mitochondrial capacity. Sixteen healthy young adults were randomly assigned in a double-blind fashion to consume either placebo or 500 mg of resveratrol plus 10 mg of piperine, a bioenhancer to increase bioavailibilty and bioefficacy of resveratrol. Participants ingested the pills daily for 4 weeks and completed 3 sessions per week of submaximal endurance training of the wrist flexor muscles of the nondominant arm. The contralateral arm served as an untrained control. Skeletal muscle mitochondrial capacity was measured using near-infrared spectroscopy. Changes in mitochondrial capacity from baseline to post-testing indicated significant differences between the resveratrol+piperine-trained arm and the placebo-trained arm (p = 0.02), with the resveratrol+piperine group increasing about 40% from baseline (Δk = 0.58), while the placebo group increased about 10% from baseline (Δk = 0.13). Neither the placebo group nor the resveratrol+piperine group exhibited changes in mitochondrial capacity in the untrained arm. In conclusion, low-intensity exercise training can increase forearm skeletal muscle mitochondrial capacity when combined with resveratrol and piperine supplementation.
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In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. Methods: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. Results: A total of 2846 (46 %) patients had no diabetes, 1158 (19 %) newly diagnosed diabetes and 2183 (35 %) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60 %, respectively. A blood pressure target of
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Background: Limited data are available indicating the effects of coenzyme Q10 (CoQ10) supplementation on metabolic status of patients with metabolic syndrome (MetS). Purpose: The present study was conducted to determine the effects of CoQ10 administration on glucose homeostasis parameters, lipid profiles, biomarkers of inflammation and oxidative stress among patients with MetS. Methods: This randomized, double-blind, placebo-controlled trial was performed among 60 overweight or obese and type 2 diabetes mellitus patients with coronary heart disease aged 40-85 years old. Participants were randomly allocated into two groups. Group A (n = 30) received 100 mg CoQ10 supplements and group B (n = 30) received placebo for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify glucose homeostasis parameters, lipid profiles and biomarkers of inflammation and oxidative stress. Results: Compared with the placebo, CoQ10 supplementation resulted in a significant reduction in serum insulin levels (-2.1 ± 7.1 vs. +4.1 ± 7.8 µIU/mL, P = 0.002) and homeostasis model of assessment-insulin resistance (-0.7 ± 2.1 vs. +1.0 ± 2.0, P = 0.002) and homeostatic model assessment-beta cell function (-5.9 ± 22.2 vs. +15.9 ± 34.0, P = 0.005). In addition, patients who received CoQ10 supplements had a significant increase in plasma total antioxidant capacity (TAC) concentrations (+26.0 ± 105.0 vs. -162.2 ± 361.8 mmol/L, P = 0.008) compared with the placebo group. However, after adjustment for the baseline levels, age and baseline BMI, the effect on TAC levels (P = 0.08) disappeared. Additionally, compared with the placebo group, a significant positive trends in plasma glutathione (P = 0.06) and a significant reduction in malondialdehyde (P = 0.08) were seen among patients who received CoQ10 supplement. We did not observe any significant changes in fasting plasma glucose, lipid concentrations and inflammatory markers. Conclusions: Overall, daily intake of 100 mg CoQ10 supplements among patients with MetS for 8 weeks had beneficial effects on serum insulin levels, HOMA-IR, HOMA-B and plasma TAC concentrations. Clinical trial registration number: www.irct.ir : IRCT201502245623N35.
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Introduction: We evaluated the association between four polymorphisms in the CRP gene with serum C-reactive protein (CRP) levels, prevalence and severity of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. Methods: We performed coronary angiography for 308 T2DM patients and classified them into two groups: T2DM with CAD and T2DM without CAD. All patients were from Ahvaz, Iran. serum levels of CRP, glucose and lipid profile were measured. Genotyping was performed by PCR/RFLP, and the severity of coronary artery disease was determined by Gensini score. Results: The GG genotype of SNP rs279421 was associated with the increased risk of CAD (OR= 2.38; 95% CI: 1.12- 5.8; p= 0.02) and CA, TT, TA genotypes and A allele of SNP rs3091244 and GA genotypes and A allele of SNP rs3093062 were significantly associated with increased CRP levels. None of genotypes or alleles was associated with Gensini score. We found that the haplotype 7 (AGCG) was associated with decreased risk of CAD (OR= 0.11; 95% CI: 0.02, 0.66; p= 0.017) and the Gensini score was correlated with increased levels of CRP, only in CAD group. Conclusion: Although genetic polymorphisms were influenced on serum RP levels, none of the alleles and genotypes raising or falling C-reactive protein levels was consistently associated with an increased prevalence of CAD or protected from that.
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Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.
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