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Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers
Abstract
Studies reported the effects of polyphenols but not for grape polyphenols towards obesity. We analysed the effects of a polyphenolic grape seed extract (GSE) on obesity and oxidative stress in hamsters receiving a high-fat diet (HFD). Three groups of hamsters received a standard diet (STD), or a HFD plus a daily gavage with water (Control, HFD) or a solution of GSE (HFD + GSE) for 12 wk. Plasma glucose, triglycerides (TG), insulin, leptin and adiponectin were measured. Oxidative stress was assessed by cardiac production of superoxide anion and NAD(P)H oxidase expression. After 12 wk, HFD increased abdominal fat as compared with standards. GSE avoided this feature. HFD led to higher plasma glucose, TG, insulin and greater insulin resistance (HOMA-IR) values. GSE prevented in part these effects, reducing insulinemia and leptinemia by 16.5 and 45%, respectively, whereas adiponectin level increased by 61% compared with obese controls. GSE lowered glycemia and HOMA-IR and strongly prevented cardiac production of superoxide by 74% and NAD(P)H oxidase expression by 30%. This is the first time that chronic consumption of grape phenolics is shown to reduce obesity development and related metabolic pathways including adipokine secretion and oxidative stress.
... Moreover, IUGR negatively affects whole-body composition and meat quality and impairs long term health [2]. In addition, IUGR has been found to be associated with immunodeficiency and increased vulnerability to infectious diseases in later life [4][5][6]. ...
... Expression of BDNF genes and proteins is higher with both concentrations, while genes regulating BDNF signalling responds more to the lower dose. (4) Lower dose modulates genes in the five highest networks associated with cellularity and neuro-cognition, while the prevention of neurodevelopmental and neurological pathologies is associated with the higher dose. ...
... Increases the length of jejunal crypts. (4) Decreases colon microbiota of E. coli. ...
Swine are one of the most important agricultural species for human food production. Given the significant disease challenges confronting commercial pig farming systems, introduction of a new feed additive that can enhance animal performance by improving growth and immune status represents a major opportunity. One such candidate is sialic acid (Sia), a diverse family of nine-carbon acidic sugar, present in various organs and body fluid, as well as an essential structural and functional constituent of brain ganglioside of humans and animals. Sias are key monosaccharide and biomarker of sialylated milk oligosaccharide (Sia-MOS’s), sialylated glycoproteins and glycolipids in milk and all vertebrate cells. Sias accomplish many critical endogenous functions by virtue of their physiochemical properties and via recognition by intrinsic receptors. Human milk sialylated glycoconjugates (Sia-GC’s) are bioactive compounds known to act as prebiotics that promote gut microbiota development, gut maturation, pathogen resistance, immunomodulation, anti-inflammation and neurodevelopment. However, the importance of Sia in pig health, especially in the growth, development, immunity of developing piglet and in pig production remains unknown. This review aims to critically discuss the current status of knowledge of the biology and nutritional role of Sia and Sia-GC’s on health of both female sow and newborn piglets.
... Researchers have also investigated the effectiveness of procyanidins in preventing oxidative stress and preserving liver integrity. In a study by Decorde et al., the researchers examined the effectiveness of polyphenolic grape seed extract (GSE) in overcoming obesity by reducing oxidative stress and addressing adipokine imbalance [56]. The study showed that procyanidins in the GSE reduced abdominal fat, insulinemia, higher plasma glucose, and leptinemia by more than 16.5% and increased the levels of adiponectin by 61% [56]. ...
... In a study by Decorde et al., the researchers examined the effectiveness of polyphenolic grape seed extract (GSE) in overcoming obesity by reducing oxidative stress and addressing adipokine imbalance [56]. The study showed that procyanidins in the GSE reduced abdominal fat, insulinemia, higher plasma glucose, and leptinemia by more than 16.5% and increased the levels of adiponectin by 61% [56]. Rodríguez-Ramiro et al. determined that cocoa polyphenolic extract together with procyanidin, are effective in preventing oxidative stress caused by dietary acrylamide, by enhancing the redox status of cells and by obstructing the apoptotic pathways created by acrylamide [57]. ...
... The effectiveness of polyphenols such as procyanidins, epicatechin, phenolic acids, carotenoids, and flavonoids in preventing a myriad of illnesses such as cancers, tumors, diabetes, heart problems, liver issues, and neurogenerative disorders is due to their activities as antioxidants [56]. Antioxidants are free radical scavengers, helping to control the production of these reactive oxygen species (ROS) that are responsible for damaging small blood vessels and releasing inflammatory cytokines that result in organ damages [58]. ...
Background:
Lifestyle involving uncontrolled alcohol consumption coupled regularly with red meat and other iron sources has detrimental effects on the liver, which in the long term, results in Alcoholic Liver Disease (ALD). Procyanidin has lately garnered increasing attention and has become the focus of research owing to its antioxidant properties. This study explores the anti-inflammatory effects of procyanidins, in preventing ALD, by analyzing the biological activities of the compound on liver injury caused by excessive alcohol and iron.
Method:
Male SPF Wistar rats were placed in 4 groups; the control Group A (basic diet); the model Group B (excess alcohol 8-12 mL/kg/d and iron 1000 mg/kg diet); the low dose procyanidin Group C (model group diet plus 60 mg/kg/d of procyanidin); and the high dose procyanidin Group D (model group diet plus 120 mg/kg/d of procyanidin). Serum biochemical markers for liver damage were measured spectrophotometrically. The NFκB and IκB mRNA expression levels were determined using RT-PCR; the NFκB p65 and IκB protein expression levels were assessed via western blotting, while ELISA was used to detect serum inflammatory factors.
Results:
The pathological score of the model Group B, low and high dose procyanidin Groups C and D were 6.58 ± 0.90,4.69 ± 0.70 and 2.00 ± 0.73, respectively (P < 0.05). The results showed that high alcohol and iron contents in the model group led to significant damage of liver structure, increased low-density lipoproteins (LDLs), steatosis, and increased levels of inflammatory cytokines. High amounts of procyanidins led to the preservation of the liver structure, production of high-density lipoproteins, and reduction in serum inflammatory cytokines while also significantly decreasing the expression levels of NFκB p65.
Conclusion:
The results prove that procyanidins have hepatoprotective potential and could be effective in reversing histopathology, possibly by alleviating inflammation and improving lipid metabolism.
... Of note, grape seed extract is known to have more OPCs responsible for higher antioxidant capacity with the ability to attenuate oxidative stress damage and inflammation [242,243]. In line with this evidence, studies have revealed that grape seed proanthocyanidins alleviate inflammation and oxidative stress by improving adipokine imbalance [244,245]. For instance, treating 3T3-L1 adipocytes with grape seed proanthocyanidins ( 150 mg/mL) promoted the crumpling of lipid droplets by increasing the secretion of adiponectin, cAMP and COX-2 in adipocytes after 12, 24, and 48 h [245]. ...
... This was further verified in vivo, whereby 25, 50, and 100 mg/kg of grape seed proanthocyanidins decreased the levels of COX-2, IL-6, and leptin, which were accompanied by a decrease in plasma glucose, total cholesterol, triglycerides, and LDL levels in HFD-induced obese rats after 4 weeks [245]. On the other hand, grape seed procyanidin extract supplementation for 12 weeks prevented HFD-induced obesity in hamsters by lowering plasma glucose and triglyceride content and reducing insulin resistance through suppressing ROS production and upregulating adiponectin secretion [244]. ...
... Accordingly, the data from preclinical in vivo studies confirm the glucose and lipid metabolism-regulating as well as hepato-and cardioprotective potential of GSE. Indeed, GSE treatment improved the insulin resistance in in vivo models of obese and fructoserich-diet rodents and attenuated pancreatic degeneration in a diabetes model [167][168][169][170][171][172][173]. In another study using healthy rats, GSE treatment following glucose intake was found to modulate glucose metabolism by upregulating the incretin GLP-1 and downregulate the GLP-1 inactivating enzyme DPP-4 [160,161,174]. ...
... Moreover, weight gain, fatty liver, adipokine level, and lipid profile were counteracted in vivo in obese or fructose-fed rodents by GSE treatment [167][168][169][176][177][178][179][180][181]. The influence of GSE on weight gain might be related to an increase in portal GLP-1, ghrelin, and decreased cholecystokinin levels, reducing gastric emptying combined with enhanced satiety and reduced food intake [182]. ...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the appearance of painful inflamed nodules, abscesses, and pus-draining sinus tracts in the intertriginous skin of the groins, buttocks, and perianal and axillary regions. Despite its high prevalence of ~0.4–1%, therapeutic options for HS are still limited. Over the past 10 years, it has become clear that HS is a systemic disease, associated with various comorbidities, including metabolic syndrome (MetS) and its sequelae. Accordingly, the life expectancy of HS patients is significantly reduced. MetS, in particular, obesity, can support sustained inflammation and thereby exacerbate skin manifestations and the chronification of HS. However, MetS actually lacks necessary attention in HS therapy, underlining the high medical need for novel therapeutic options. This review directs attention towards the relevance of MetS in HS and evaluates the potential of phytomedical drug candidates to alleviate its components. It starts by describing key facts about HS, the specifics of metabolic alterations in HS patients, and mechanisms by which obesity may exacerbate HS skin alterations. Then, the results from the preclinical studies with phytochemicals on MetS parameters are evaluated and the outcomes of respective randomized controlled clinical trials in healthy people and patients without HS are presented.
... The health benefits associated with these compounds have led to position them as possible anti-obesity metabolites due to their anti-obesogenic and pro-thermogenic characteristics [37][38][39][40][41][42][43][44][45]. A strawberry extract rich in flavonoids (1.02 ± 0.87 mg catechin equivalent/g FW) treatment decreased intracellular lipid accumulation in HepG2 cells and resulted in higher expression of the LDL-receptor, SIRT1, PGC-1α, and p-AMPK/AMPK. ...
... The treated group presented a higher mitochondrial activity and oxygen consumption rate with an increment in SIRT1, PGC-1α, and p-AMPK expression in isolated liver mitochondria, which was reversed in the presence of compound C [47]. Moreover, grape procyanidins (flavonoids) have been involved in preventing obesity in HFD-fed hamsters, improving their adipokine secretory profile and attenuating oxidative stress [38]. Polyphenol-rich extracts from apple and cinnamon also prevented obesity in rats [40]. ...
Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation.
... GSPE has a wide range of pharmacological and therapeutic effects. Hamsters fed with GSPE, have reduced levels of oxidative stress [15]. Furthermore, GSPE prevents ethanolinduced DNA damage in mouse brain cells through its antioxidation activity [16], and protects against H2O2-induced DNA damage in Fao cells [13]. ...
... Previous studies have shown that the addition of antioxidants can significantly improve sperm quality in the rat [22], bull [11], dog [12], boar [8], and ram [5] by reducing ROS accumulation during the preservation process. GSPE has been reported to have a strong antioxidant capacity [13,15,16,23]. The results of this study demonstrated that the addition of GSPE to the extender enhanced goat sperm quality and antioxidant capacity during liquid preservation at 4 °C. ...
Grape seed procyanidin extract (GSPE) has been shown to possess antioxidative effects. This experiment was designed to study the effect of GSPE during the liquid storage of goat semen. Semen samples were collected from six sexually mature goats. The samples were treated with different concentrations of GSPE (10, 30, 50, and 70 mg/L) in basic diluent and stored at 4 °C for 120 h; samples without GSPE were used as the control group. The results showed that sperm motility, acrosome membrane integrity, mitochondrial activity, plasma membrane integrity, total antioxidative capacity (T-AOC), catalase (CAT) activity, and superoxide dismutase (SOD) activity in the treatment groups were significantly higher than in the control group, whereas malondialdehyde (MDA) content was lower than in the control group (p < 0.05). In the treatment group, sperm quality in the 30 mg/L GSPE group was significantly higher than the other groups (p < 0.05). Furthermore, artificial insemination (AI) results showed that litter sizes were higher in the 30 mg/L GSPE group than in the control group (p < 0.05). In summary, this experiment showed that adding GSPE to the basic diluent improved sperm quality and that 30 mg/L of GSPE was the most suitable concentration for the liquid preservation of goat semen at 4 °C.
... Moreover, they may improve glucose metabolism by reducing plasma glucose, and ameliorate hyperlipidaemia, being able to reduce levels of TG, TC and LDL-cholesterol in plasma. Plant extracts can act enhancing NO bioavailability as a result of an increase of NO, eNOS activity, and/or reduction of superoxide anion production (Lin et al. 2007, Uchiyama et al. 2011, Min et al. 2013, Herranz-L opez et al. 2015, D ecord e et al. 2009, Agouni et al. 2009, Bargall o et al. 2006, Gourineni et al. 2012, Villalpando-Arteaga et al. 2013 (Table 2). Another studies also suggests other mechanisms; as an example, an olive leaves extract was able to regulate the expression of genes involved in adipogenesis and thermogenesis in the visceral adipose tissue , while olive oil could enhance fat oxidation and regulate myocardial metabolic enzymes, that lead to optimize cardiac energy metabolism (Ebaid et al. 2010). ...
... Several clinical trials carried out using grape extracts have suggested their cardioprotective effect reducing the atherogenic markers or improving the lipidic profile (Kar et al. 2009, Tom e-Carneiro et al. 2012. However, despite, in vitro and in vivo studies have shown the potential of grape and grape-seed extracts on obesity management (D ecord e et al. 2009(D ecord e et al. , Zhang et al. 2012, little is known about its effect in clinical practices. Han et al. (2016) examined the efficacy of grape pomace and omija fruit ethanol extract on metabolic disorders in 76 in overweight or obese subjects with promising results lowering TC, LDL-C and improving HDL-C plasma concentrations. ...
Prevalence of obesity worldwide has reached pandemic proportions. Despite the increasing evidence in the implication of phenolic compounds in obesity management, the real effect is not completely understood. The available in vitro and in vivo studies have demonstrated the implication of phenolic compounds in: lowering food intake, decreasing lipogenesis, increasing lipolysis, stimulating fatty acids β-oxidation, inhibiting adipocyte differentiation and growth, attenuating inflammatory responses and suppress oxidative stress. This review encompasses the most recent evidence in the anti-obesity effect of phenolic compounds from plants to different nutraceuticals and functional foods based on the in vitro, in vivo and clinical studies. For that, this review has been focused on popular plant-based products highly consumed today such as cocoa, cinnamon, and olive oil, beverages such as red wine, tea (green, white and black tea) and Hibiscus sabdariffa L. tea, among others.
... An extract from the pomace of the red American grape Norton induced anti-inflammatory effects in mice fed a high-fat (HF) diet and exhibited in vitro antioxidant activity [10]. An extract containing mainly procyanidin from Chardonnay grape seeds reduced oxidative stress markers and obesity in HF diet-induced obese (DIO) hamsters [11]. An extract from a pomace from five red and three wine grapes reduced obesity and insulin resistance and inhibited hepatic expression of genes involved in lipogenesis, gluconeogenesis, and inflammation in rats on a HF diet [12]. ...
... The in vivo biological significance of in vitro activity is not clear because oligomers and larger flavonoids are poorly absorbed, while monomers are rapidly metabolized and cleared from the body. Nonetheless, previous studies reported that flavonoid-rich grape seed extract reduced oxidative stress markers in obese hamsters and human subjects [11,37,38]. In the present study, ChrSd supplementation down-regulated expression of stress responsive genes, Gdf15 and ChREBP. ...
To identify differentially expressed hepatic genes contributing to the improvement of high-fat (HF) diet-induced hepatic steatosis and insulin resistance following supplementation of partially defatted flavonoid-rich Chardonnay grape seed flour (ChrSd), diet-induced obese (DIO) mice were fed HF diets containing either ChrSd or microcrystalline cellulose (MCC, control) for 5 weeks. The 2-h insulin area under the curve was significantly lowered by ChrSd, indicating that ChrSd improved insulin sensitivity. ChrSd intake also significantly reduced body weight gain, liver and adipose tissue weight, hepatic lipid content, and plasma low-density lipoprotein (LDL)-cholesterol, despite a significant increase in food intake. Exon microarray analysis of hepatic gene expression revealed down-regulation of genes related to triglyceride and ceramide synthesis, immune response, oxidative stress, and inflammation and upregulation of genes related to fatty acid oxidation, cholesterol, and bile acid synthesis. In conclusion, the effects of ChrSd supplementation in a HF diet on weight gain, insulin resistance, and progression of hepatic steatosis in DIO mice were associated with modulation of hepatic genes related to oxidative stress, inflammation, ceramide synthesis, and lipid and cholesterol metabolism.
... To determine whether peripheral signals that indicate the status of the body's energy storage have a role in food intake control, we analyzed leptinemia and found no changes due to GSPE treatments. Chronic long-term treatment with doses without properties on food intake have proven effective in limiting the increase in leptinemia related to a high-fat diet in hamsters [51,52], but corrective GSPE doses for shorter periods (30 days) did not revert the higher leptinemia [51]. Thus, the different studies, working with different doses, show inconsistent results that prevent clear conclusions from being drawn regarding the effect of GSPE on leptin production. ...
... To determine whether peripheral signals that indicate the status of the body's energy storage have a role in food intake control, we analyzed leptinemia and found no changes due to GSPE treatments. Chronic long-term treatment with doses without properties on food intake have proven effective in limiting the increase in leptinemia related to a high-fat diet in hamsters [51,52], but corrective GSPE doses for shorter periods (30 days) did not revert the higher leptinemia [51]. Thus, the different studies, working with different doses, show inconsistent results that prevent clear conclusions from being drawn regarding the effect of GSPE on leptin production. ...
Food intake depends on homeostatic and non-homeostatic factors. In order to use grape seed proanthocyanidins (GSPE) as food intake limiting agents, it is important to define the key characteristics of their bioactivity within this complex function. We treated rats with acute and chronic treatments of GSPE at different doses to identify the importance of eating patterns and GSPE dose and the mechanistic aspects of GSPE. GSPE-induced food intake inhibition must be reproduced under non-stressful conditions and with a stable and synchronized feeding pattern. A minimum dose of around 350 mg GSPE/kg body weight (BW) is needed. GSPE components act by activating the Glucagon-like peptide-1 (GLP-1) receptor because their effect is blocked by Exendin 9-39. GSPE in turn acts on the hypothalamic center of food intake control probably because of increased GLP-1 production in the intestine. To conclude, GSPE inhibits food intake through GLP-1 signaling, but it needs to be dosed under optimal conditions to exert this effect.
... According to certain studies, cyanidin and its glycosides are found in foods where lower levels of atherogenic lipoprotein and oxidized low-density lipoprotein (LDL) are produced both in vitro (Meyer et al. 1998) and in vivo (Abdel-Moemin 2011). Moreover, several studies have shown that the consumption of a diet rich in cyanidin effectively mitigates the adverse effects of a high-fat diet, including body weight increase, hyperglycemia, and hyperinsulinemia, via the enhancement of adipokine production (Décordé et al. 2009) and hormone-sensitive lipase (Dallas et al. 2008). Jia et al. discovered that cyanidin has the greatest affinity for direct binding to all three PPAR isoform subtypes and that this direct binding results in common agonistic effects. ...
The hepatic manifestation of metabolic syndrome, associated with various metabolic diseases such as type 2 diabetes, insulin resistance, and high cholesterol, is called non-alcoholic fatty liver disease (NAFLD). Despite several research efforts, no approved medicine is currently available for the treatment of this illness. Swiss Target Prediction was used to screen phytochemicals. To examine potential targets, the protein-protein interaction (PPI) network was developed. Cytoscape was used to create the component-target-pathway (C-T-P) network, and AutoDock was used to assess molecular docking. Antioxidant and anti-inflammatory qualities were tested in vitro. Naringenin, ellagic acid, and cyanidin were found to be the main active components. As important targets, PPARA, PPARG, and AKT1 were selected. Through enrichment analysis, a total of 20 crucial signaling pathways, including insulin resistance (IR), NAFLD, relaxin, PI3K-Akt, HIF-1, AGE-RAGE, and MAPK, were identified. The in silico computational techniques predicted the molecular pathway for the active ingredients and the disease targets, thus helping to further research.
... Grape seed extract has shown beneficial effects in many diseases, thanks to its composition as a flavonoid polyphenolic compound; its main components are: +catechin, −epicatechin gallate, gallate and −epigallocatechin [230]. Beneficial properties of grape seed include prevention and treatment of diabetes and its complications [231], prevention of obesity and inflammatory reaction [232,233], the ability to modify early cerebrovascular injury caused by hypertension [234], alleviation of exercise fatigue [235], protection of the myocardium from injury [236], lowering blood lipids, regulating the metabolism, and improving the intestinal flora [237,238]. Most of these activities are carried out thanks to the antioxidant effect of grape seed extract, which makes it more powerful and effective than other plant polyphenolic compounds [239,240]. ...
Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders.
... In another study, treatment of mice pancreatic islets with grape seed, skin, and stem extracts in the presence of 5.5 mM and 16.5 mM glucose concentration, resulted in a two to eightfold increase in insulin secretion, suggesting insulinotropic effects of grape pomace (Doshi et al., 2015). Hamsters fed a high fat diet supplemented with a polyphenolic grape seed extract (7.14 mL/ kg) for 12 weeks, exhibited lower plasma insulin and glucose concentrations as well as NADPH oxidase downregulation (Décordé et al., 2009). Supplementation of a high-fat diet with 5%, 10%, and 15% of grape pomace for 60 days in rats, resulted in a significant reduction in total cholesterol levels and lower concentrations of triglycerides, LDL, and vLDL (Thabet, 2020). ...
Wheat flour is the major constituent of bakery products consumed as everyday snacks worldwide. However, due to its poor nutritional value, high gluten content, and rapid digestion has been linked to the onset of celiac disease, obesity, diabetes type II, and metabolic syndrome. Therefore, alternative flours from olive and grape by-products as well as pulses, such as chickpea, with higher nutritional value and prebiotic function have been exploited to enrich those products and possibly confer several health benefits due to their high bioactivity. To this end, the bioactivity of grape and olive by-products as well as chickpea is described. This study emphasizes the crucial function of the related compounds in human nutrition and metabolism, particularly in relation to post-prandial glycemia and lipidemia, as their acute perturbation is linked to the development of metabolic diseases. Dietary supplementation with either chickpea, olive or grape pomace extracts or powders in in vivo and in vitro studies demonstrated beneficial properties in terms of glucose and lipid metabolism management. Moreover, hepato- and cardio-protective, antioxidant, and anti-inflammatory properties were observed. Furthermore, fortification of bakery snacks with chickpea, olive, and grape pomace flours demonstrated promising results in improving the lipid and glycemic profiles in human intervention studies.
... ese results can be attributed to the duration of the experimental period since the total time of the hyperlipidemic diet was only 7 weeks and other studies used protocols of longer duration to induce obesity in hamsters, with 12 to 16 weeks, and despite this, there were no differences in relation to weight gain among groups, probably due to the higher amount of kcal/g in hyperlipidemic diet [42][43][44]. ...
This study aimed to evaluate the effects of the treatment with bacuri seed butter (BB) on body weight, growth, body mass index, lipid profile, atherosclerotic indices, and liver function in dyslipidemic hamsters. Freshly weaned, male hamsters were divided into four groups: (1) normal group (NG)—maintained with standard chow (AIN-93G); (2) dyslipidemia group (DG)—maintained with hyperlipidemic chow (AIN-93G modified) throughout the follow-up period; (3) bacuri seed butter 25 mg/kg/day (BB-25); and (4) bacuri seed butter 50 mg/kg/day (BB-50). BB groups (25 and 50 mg/kg/day) were also maintained with hyperlipidemic chow throughout the follow-up period, and the treatment started after 21 days receiving a hyperlipidemic diet to induce hypercholesterolemia and maintained for 28 days. No significant differences in triglycerides and total cholesterol were observed for BB-25 and BB-50 groups when compared with NG and DG groups. On the contrary, BB-25 and BB-50 induced both increase of HDL-c (51.40 ± 1.69 and 51.00 ± 2.34, respectively) and decrease of LDL-c (103.80 ± 6.87 and 100.50 ± 3.95, respectively) when compared with DG (41.00 ± 2.94 and 132.70 ± 9.41, respectively). In addition, BB promoted a reduction in the risk of atherosclerotic disease by decreasing p<0.05 the atherogenic index, coronary artery risk index, and LDL/CT ratio p<0.05 and increasing HDL/CT ratio. On the contrary, no changes were observed in total cholesterol and triglyceride levels or in body weight, growth, body mass index, or liver function parameters. Thus, bacuri seed butter at doses of 25 and 50 mg/kg/day has positive repercussions on the lipid profile, more precisely on plasma HDL-c and LDL-c, and additionally promotes reduction in the risk of atherosclerosis in hamsters.
... Procyanidins have outstanding biological activities, such as lowering plasma lipids, scavenging free radicals, and resisting inflammation. 27,28 Bioactive procyanidins with considerable health-promoting effects are the most abundant polyphenols in human diets. In the present study, we focused on the effect of PCA2, an A-type procyanidin, on HFD-induced AS mice with intact and antibiotic-depleted gut microbiota. ...
... GSE is known to have many beneficial health properties, including protection against hypertension [23], the prevention and treatment of diabetes [24], and the prevention of obesity [25]. In addition, the incidence and growth of UVB radiation-induced photocarcinogenesis of skin cancer was effectively prevented by the dietary feeding of GSE [26]. ...
Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.
... Procyanidins have outstanding biological activities, such as lowering plasma lipids, scavenging free radicals, and resisting inflammation. 27,28 Bioactive procyanidins with considerable health-promoting effects are the most abundant polyphenols in human diets. In the present study, we focused on the effect of PCA2, an A-type procyanidin, on HFD-induced AS mice with intact and antibiotic-depleted gut microbiota. ...
Plum (Prunus Salicina Lindl) is a rich source of phenolic compounds. However, the bound phenolics and its bioaccessibility and antioxidant activity remain unclear. Hence, the purpose of this study was to determine: 1) phenolic profiles of plum, including both free and bound phenolic fractions, 2) bioaccessibility of phenolic compounds in plum during simulated gastrointestinal digestions, 3) their antioxidant properties. A total of 17 phenolic compounds were identified by UPLC-Q-Exactive Orbitrap/MS with most epicatechin, neochlorogenic acid and procyanidin B2 in the free phenolics fraction, while catechin and epicatechin was the main compounds in the bound phenolics fraction. After the gastrointestinal digestion phase, the most bioaccessible phenolics were quercetin-pentoside (61.64%), cyanidin-3-O-glucoside (43.26%), and naringenin-7-O-β-D-glucoside (42.04%). The antioxidant capacity of both undigested plum and its digested fractions showed a positive correlation with the total phenolics, and with specific individual phenolic compounds such as neochlorogenic acid, epicatechin and procyanidin B2 in undigested plum whereas catechin, neochlorogenic acid, and epicatechin in digested one. The results confirm that bound fraction of plum contribution to the total phenolic content must be taken into account in the assessment of the improving human health effects of plum.
... Il a également été étudié les propriétés organoleptiques des polyphénols sur l'amertume et l'astringence. En effet, l'amertume des flavan-3-ols et des tanins a été depuis longtemps observée [14] ainsi que leur astringence [15][16][17][18][19]. La conformation stéréochimique des groupements hydroxyles sur les hétérocycles [17,20] Les polyphénols ont aussi été largement étudiés pour leurs effets sur la santé, « french paradox » [29,30], et leur implication dans la prévention des cancers [31], maladies cardiovasculaires [32][33][34][35][36][37], neurodégénérescence [38] et autres pathologies [39][40][41][42][43][44][45][46][47]. Ces implications peuvent être expliquées par leurs propriétés antioxydantes [44,[48][49][50][51][52][53] et leurs interactions avec des protéines (kinases, facteur de transcription…) qui permettent une inhibition des enzymes productrices d'espèces réactives de l'oxygène (ERO) ou une stimulation de la synthèse d'enzymes antioxydantes [54,55]. ...
Lors de l’élevage des vins avec le bois de chêne, plusieurs molécules d’intérêts organoleptiques comme les ellagitanins (vescalagine, castalagine, roburines A, B, C, D, E et grandinine), sont extraites. Leurs concentrations dans le bois et le vin sont très variables et leurs cinétiques d’extraction au cours de l’élevage ainsi que leurs propriétés organoleptiques dans les vins sont mal connues. Dans le but de classifier chaque douelle pour fabriquer des barriques avec des indices en polyphénols (IP) totaux significativement différents, un système proche infrarouge (NIRS), Oakscan®, a été mis en place par la tonnellerie Radoux. Notre objectif était d’étudier l’influence de ce mode de classifications des bois au niveau de la composition moléculaire et organoleptique des vins. Dans un premier temps, la classification NIRS des bois de chêne a été confirmée par quantification des concentrations en ellagitanins totaux et moléculaire par HPLC-UV-MS. Une forte variabilité des concentrations en ellagitanins des bois est observée entre 5,95 et 32,91 mg d’équivalent acide ellagique/g de bois. De plus, la classification NIRS des bois se corrèle avec les analyses chimiques (p < 0,02%). Cette nouvelle méthode permet donc de fabriquer des barriques avec un IP moyen différent (IP : 11 à 70). Dans un second temps, des vins de différentes origines et cépages sont élevés dans les barriques classifiées. La cinétique des teneurs en ellagitanins montre l’influence de la classification des bois de chêne (p < 5%). En effet, dès les premiers mois d’élevage, une augmentation en ellagitanins jusqu’à un maximum est obtenue. Plus les bois sont riches, plus le maximum de concentration en ellagitanins des vins est élevé et décalé dans le temps. Puis, une lente diminution des concentrations en ellagitanins est observée. Les influences du grain et de la chauffe des bois ont également été analysées. La solubilisation dans les vins des composés aromatiques des bois de chêne classifiés par Oakscan® montre dans plusieurs cas que les teneurs en aldéhydes furaniques et en syringol impliqués dans les perceptions du fumé/grillé sont corrélées avec la classification NIRS et également avec l’IP des bois. Ainsi, un vin élevé au contact de bois riches en polyphénols possède des concentrations en arômes fumé/grillé plus importantes. Néanmoins, l’intensité de la chauffe a un rôle prépondérant sur les concentrations de ces arômes boisés. Parallèlement, les propriétés organoleptiques des vins élevés avec du bois de chêne à 6, 12, 18 ou 24 mois et testées par un jury entrainé, montrent des différences significatives corrélées à l’IP des barriques. Les vins élevés au contact des IP les plus importants sont significativement décrits comme plus boisés, fumés/grillés et épicé au nez. En bouche, l’amertume et l’astringence sont significativement plus importantes pour les vins élevés dans les barriques possédant les plus fortes concentrations en ellagitanins. A contrario, le fruité des vins, au nez et en bouche, est généralement noté comme moins important pour les vins élevés avec des barriques à IP le plus haut.L’influence de la classification des bois, en fonction de leurs grains et de leurs IP, sur la consommation en oxygène des vins rouges a été suivie grâce à une méthode innovante et non invasive. Les résultats montrent que 96% de l’oxygène dans le vin à T0 est consommé huit jours après entonnage. Des différences significatives (p < 0,01%), entre les vitesses de consommation de l’oxygène et l’IP ou le grain des barriques, sont observées. La vitesse de consommation d’oxygène augmente en corrélation de l’IP des barriques ou de la taille du grain. Ces résultats permettent d’envisager l’utilisation de méthodes de sélection non empiriques et fiables des bois de chêne en fonction de leurs grains ou de leurs concentrations en ellagitanins ce qui permet de fabriquer des barriques classifiées à l’aide de nos résultats conférant, au vin, des propriétés organoleptiques maîtrisées.
... Among healthy males, the effects of alcohol consumption on sex hormones has been shown to vary by drinking pattern and between beer and wine consumption (Couwenbergs, 1988;Nishizawa et al., 2002;Rinaldi et al., 2006), such that the type of alcoholic beverage consumed and specifically its polyphenol content may differentially affect adiponectin concentrations. Moreover, in an animal model, the chronic consumption of grape-derived polyphenols was found to prevent diet-induced obesity by improving oxidative stress markers such as adipokine secretion (Décordé et al., 2009). ...
Accumulating evidence suggests that regular moderate consumption of wine can positively influence risk factors associated with cardiovascular health. These effects are often attributed to grape and wine-derived phenolic compounds and their effects on risk factors such as atherosclerosis, for which mechanisms have been clearly identified, such as a decrease in the oxidation of LDL-cholesterol and reduction of oxidative stress, and an increase in nitric oxide and related restoration of endothelial function. In addition, the ethanol component of wine increases HDL-cholesterol, inhibits platelet aggregation, promotes fibrinolysis and reduces systemic inflammation. Scientific research needs to be conducted, however, before we can begin to provide science-based dietary recommendations, although there is sufficient evidence to generally recommend consuming food sources rich in bioactive compounds such as wine in moderation. This narrative review examines published evidence on the cardioprotective effects associated with wine-derived compounds, with a primary focus on the development and progression of atherosclerosis and thrombosis.
... More specifically, grape seed extracts (GSE) from the seeds of Vitis vinifera, are sources of flavonoids, particularly proanthocyanidins (POC) that are known to have beneficial effects on oxidative stress and on many metabolic disorders including insulin resistance [16], increased adiposity [17], and inflammation [18] in mammals. Moreover, it has been reported that some of these GSE effects could be associated to modulations of plasma adipokines such as adiponectin [19]. In mammals, different studies have demonstrated that maternal consumption of polyphenols including GSE during prenatal periods can positively affect the health of the offspring [20][21][22][23][24][25][26]. ...
In reproductive hens, a feed restriction is an usual practice to improve metabolic and reproductive disorders. However, it acts a stressor on the animal. In mammals, grape seed extracts (GSE) reduces oxidative stress. However, their effect on endocrine and tissue response need to be deepened in reproductive hens. Here, we evaluated the effects of time and level of GSE dietary supplementation on growth performance, viability, oxidative stress and metabolic parameters in plasma and metabolic tissues in reproductive hens and their offsprings. We designed an in vivo trial using 4 groups of feed restricted hens: A (control), B and C (supplemented with 0.5% and 1% of the total diet composition in GSE since week 4, respectively) and D (supplemented with 1% of GSE since the hatch). In hens from hatch to week 40, GSE supplementation did not affect food intake and fattening whatever the time and dose of supplementation. Body weight was significantly reduced in D group as compared to control. In all hen groups, GSE supplementation decreased plasma oxidative stress index associated to a decrease in the mRNA expression of the NOX4 and 5 oxidant genes in liver and muscle and an increase in SOD mRNA expression. This was also associated to decreased plasma chemerin and increased plasma adiponectin and visfatin levels. Interestingly, maternal GSE supplementation increased the live body weight and viability of chicks at hatching and 10 days of age. This was associated to a decrease in plasma and liver oxidative stress parameters. Taken together, GSE maternal dietary supplementation reduces plasma and tissue oxidative stress associated to modulation of adipokines without affecting fattening in reproductive hens. A 1% GSE maternal dietary supplementation increased offspring viability and reduced oxidative stress suggesting a beneficial transgenerational effect and a potential use to improve the quality of the progeny in reproductive hens.
... It exists in the form of monomer and polymer (Fig. 1) [24,25]. Compared with other plant-derived polyphenols; GSPE has more beneficial health properties, including the ability to modify early cerebrovascular injury caused by hypertension [26], protection of the myocardium from injury [27,28], prevention and treatment of diabetes and its complications [29], alleviation of exercise fatigue [30] and prevention of obesity and inflammatory reaction [31,32]; it is considered as one of the most effective plant antioxidants, and one of the most effective free radical scavengers [33,34]. By studying the relationship between GSPE and obesity, we found that GSPE has many activities, such as lowering blood lipid, improving the intestinal flora, regulating the metabolism and so on [35,36]. ...
Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment.
... Grape seed extract (GSE) is a nutritional supplement with important health benefits 9, Because it is a complex mixture of polyphenols consist of flavonoids and nonflavonoids compounds 10 . This plant extract has many benefits include cardioprotective benefits 11 , Renoprotective 12 as well as neuroprotective 13 . The grape seed extract GSE known for its ability to treat anemia and has various biological functions due to it rich polyphenol ingredients 14 , Therefore, it was used in this study to verify its role in reducing the effects of thyroid disorders on some blood parameters. ...
To evaluate the role of grape seed extract in mitigation the effects of thyroid disorders on some blood parameters, Sixty healthy male white rats were used in the current study, divided in six groups (n=10) each group treated as flow: control group (C) given distil water for 45 days. First treatment (T1) given oral dose of 30 mg/kg carbimazole for 45 days as control positive, Second treatment (T2) given oral dose of 20mg/kg L-thyroxin for 45 days as control positive, Third treatment (T3) given oral dose of 150mg/kg GSE for 45 days as control negative, Fourth treatment (T4) given oral dose of 30mg/kg carbimazole for 15 days to induced hypothyroidism then given 30mg/kg carbimazole synchronously with 150mg/kg GSE for 30 days. Fifth treatment (T5) given oral dose of 20mg/kg L-thyroxin for 15 days to induced hyperthyroidism then given 20mg/kg L-thyroxin synchronously with 150mg/kg GSE for 30 days. The results (table1) showed that there was no significant decrease (P>0.05) in RBC result in T1 but was there significant increase (P<0.05) in T2 treatment compared with control, while results showed significant decrease (P<0.05) in each of PCV, Hb and ESR in booth T1 and T2 treatments compared with control, Total count of WBC results (table 2) showed significant increase (P<0.05) in T1 and significant decrease (P<0.05) in T2 compared with control, This was accompanied by significant differences in MO, ECIDO, LY and NE when comparing the results of these parameters in T1 and T2 treatments with control. As for T3 treatment which in turn were closely related without no significant difference with control group. Fourth group results experienced improvement in RBCs and Hb closely to control whereas PCV parameter was relative to control and also not significantly different from its rate in the first group, ESR results in this group did not differ significantly compared with control group while WBC results decreased significantly (P<0.05) compared with control and T1. The fifth group result they were close to normal range of all parameters in control group as well as compared with third treatment, in contrast results of this fifth treatment were differ significantly towards improvement in these parameters compared with second group which treated with L-thyroxin alone. According to these results we can conclude that grape seeds extract have important role in mitigation thyroid disorders on blood parameters.
... Phytochemicals such as polyphenols are compounds that possess antioxidant, anti-inflammatory, anti-cancer, anti-obesity and anti-aging properties (Joseph, Edirisinghe, & Burton-Freeman, 2016;Niedzwiecki, Roomi, Kalinovsky, & Rath, 2016;Papaevgeniou & Chondrogianni, 2018;Wang et al., 2014). Catechins, anthocyanins (ACN), resveratrol and curcumins are a few examples of polyphenols that have demonstrated the ability to modulate physiological and molecular pathways involved in energy metabolism, adiposity and obesity (Decorde et al., 2009;Jin, Song, Weng, & Fantus, 2018;Panickar, 2013;Puglisi & Fernandez, 2008;Wang et al., 2014;Wu et al., 2013). Currently up to six hundred different, naturally occurring ACN have been discovered (Liu et al., 2018). ...
Chronic low-grade inflammation in obese and overweight individuals is associated with an increased risk of type II diabetes and cardiovascular disease. The current trial investigated the anti-inflammatory properties of anthocyanin (ACN) supplementation in lean, overweight and obese individuals. Fifteen lean, ten overweight and ten obese participants consumed ACN (320 mg/day) for 28 days along with their usual diet. ACN supplementation significantly decreased blood plasma levels of CCL2 in the lean, overweight and obese groups (p < 0.0001, p < 0.0001 and p < 0.01 respectively). Additionally, significantly decreased levels of IL-6 in the obese group (p < 0.05) were also observed post-ACN supplementation. In conclusion, these results demonstrate the anti-inflammatory potential of ACN and suggest the supplementation of ACN as a complementary therapeutic agent for reducing chronic inflammation in obese and overweight individuals.
... Since then, interest and research regarding these compounds have increased significantly. For example, it has been described that grape procyanidins have a preventive effect for obesity in hamsters fed with a high-fat diet, improving the adipokine secretory profile of adipose tissue and attenuating oxidative stress [55]. Additionally, isolated effects of polyphenols have been observed, such as resveratrol and quercetin, which synergize reducing fatty deposits in rats [56]. ...
Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health.
... The energy content of the grape seed could have been reduced compared to that of control, which could lead to a lower milk production and thus to a lower energy deposition of fat. By the other hand, phenolic compounds maybe transferred to milk could have also reduced obesity in lambs, as it was observed in hamsters supplemented with grape seed procyanidin extract 35 . ...
Introduction - Winery by-products, which may constitute undesirable waste, can be used as feeding supplements in ruminants, but they could modify product quality. Aim - To investigate the effect of wine by-products added to lactating ewes feeding on the ewe’s welfare, milk quality and their suckling lamb performance, carcass and meat quality. Material and methods - A total of 42 Chamarita breed ewes were allocated in one of three experimental diets: a control, based in concentrates without added by-product, and diets supplemented with either 10% grape pomace or 5% grape seed on a dry matter basis, during middle gestation and lactation. Ewe’s physiological welfare indicators and milk quality were assessed, and daily gain, carcass and meat quality (pH, cooking and thawing losses, texture and colour) in their suckling lambs were analysed. Results and discussion - Compared to the control group, cortisol levels was higher in the ewes fed pomace; whereas creatine kinase and non-esterified fatty acids were superior in the ewes fed seed. However, milk composition was minimally affected, showing less lactose concentration the grape pomace and control groups, but the percentage of fat and protein and somatic cell count was similar between treatments. The suckling lambs showed similar performance, but the fattening carcass score of the lambs of the grape seed group was lower than control. The meat of the three treatments reached a similar pH, cooking loss and instrumental texture and only a minor effect in thawing loss and the colour parameter lightness was observed. Conclusion - The inclusion of grape by-products may be used as a supplementation in lactating ewes without compromising lambs’ growths, carcass composition and instrumental meat quality.
... Quercetin supplementation led to an increase in mitochondrial density [44], and increased the endurance without previous training [95]. Reports about the efficacy of these polyphenols on metabolic rate, substrate oxidation and energy expenditure in humans are still scarce, but it is a promising field of investigation, considering the beneficial effects of grape extracts (rich in resveratrol and quercetin) in preventing obesity [96], and in reducing weight gain [97]. Studies with oleuropein, a phenolic compound found in extra virgin olive oil, have been shown to increase catecholamine secretion and increase UCP1 expression [98]. ...
Obesity is a health problem worldwide, and energy imbalance has been pointed out as one of the main factors responsible for its development. As mitochondria are a key element in energy homeostasis, the development of obesity has been strongly associated with mitochondrial imbalance. Polyphenols are the largest group of phytochemicals, widely distributed in the plant kingdom, abundant in fruits and vegetables, and have been classically described as antioxidants owing to their well-established ability to eliminate free radicals and reactive oxygen species (ROS). During the last decade, however, growing evidence reports the ability of polyphenols to perform several important biological activities in addition to their antioxidant activity. Special attention has been given to the ability of polyphenols to modulate mitochondrial processes. Thus, some polyphenols are now recognized as molecules capable of modulating pathways that regulate mitochondrial biogenesis, ATP synthesis, and thermogenesis, among others. The present review reports the main benefits of polyphenols in modulating mitochondrial processes that favor the regulation of energy expenditure and offer benefits in the management of obesity, especially thermogenesis and mitochondrial biogenesis.
... would have the same effect, long term, for people. Although the rinds of fruits like oranges do contain PMFs, they may not contain them in such a quantity as to make a difference in cholesterol levels [6][7][8][9][10][11][12] . A compound found in the peels of citrus fruit has the potential to lower cholesterol more effectively than some prescription drugs, and without side effects [13][14][15][16][17] . ...
ESTIMATION OF CHOLESTEROL, EGG CHOLESTEROL AND THE EFFECT OF
ORANGE PEEL, GRAPE SEEDS AND GOOSEBERRY ON THEM USING HPTLC
... More recently, the attenuation of obesity induced inflammation by grape seed PAs were demonstrated by molecular methods. Décordé et al. [55] determined the expression of adipocytokines in hamsters on high fat diets supplemented with Chardonnay grape seed extracts for 12 weeks. The extract was reported to contain 448 mg$g -1 polymeric tannins as leucocyanidin equivalents. ...
Obesity is increasing in developing countries. Population studies show a relationship between affluence and obesity. Changing food intake patterns with affluence such as preference for foods with less astringent polyphenolic compounds and dietary fibers may increase risk of metabolic dysfunctions due to caloric imbalance. Animal models of obesity consistently show that grape seed procyanidins prevent increases in body and abdominal adipose weight gain, plasma cholesterol, liver weight gain and inflammation in animals on high fat diets. The mechanisms are not clear because the oral intake of procyanidins results in pleiotropic interactions with proteins in the mouth, stomach, small intestine, cecum and colon that affect the rate of digestion of bioavailability of macronutrients, sterols, and dietary fiber. Procyanidins also bind bile acids and reduce intestinal permeability to inflammatory bacterial cell wall fragment. Procyanidins are not degraded or metabolized until reaching the lower gut where they can be metabolized into phenolic acids by gut bacteria. While they are metabolized by gut bacteria, they also alter total numbers and distribution of phyla and species of gut bacteria. Gut bacteria are recognized as significant contributors to obesity and obesity related metabolic diseases. The review examines the different pleiotropic effects of grape seed procyanidins that have a significant effect on metabolic disease in animal models of obesity.
... 28,40 Chronic consumption of grape phenolics improved oxidative stress markers by preventing in part NAD(P)H oxidase expression in the left cardiac ventricle in high-fat diet-induced obesity hamsters. 41 Rats supplemented with standard grape extract at a dose of 100 and 200 mg kg −1 day −1 for three weeks reduced myocardial ischemia reperfusion injury attributed to its in vitro antioxidant effect. 42 Moreover, supplementation with red wine polyphenols and red grape skin polyphenolic extract enriched with anthocyanins prevented hypertension, cardiac hypertrophy and production of reactive oxygen species in high fructose-fed rats. ...
This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds, on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar–Kyoto (WKY) rats fed a high fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e. peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue “browning” i.e. PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 upregulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate the addition of GPE (30 μM) activated the β-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated upregulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.
... The phenolic compounds have various biologically important functions such as radical scavenging, antioxidants and other health promoting properties [17,18]. Prolonged consumption of phenolic compounds is associated with prevention and reduction of obesity and effects on metabolic pathways such as secretion of adipokine and oxidative stress [19]. They can also be recommended as natural food additives and preferred over synthetic antioxidants such as BHA and BHT [17]. ...
Aims and background:
Aseptic processing is focused only fruit juices, but the processing of strengthful fruit, like fruit juice fortified with other beneficial herbs by tetrapack processing has not been attempted. The aim of the study to introduce a new form of orange juice with a good nutritional value.
Materials and methods:
Orange-Mint leaves juice was formulated using different addition percentages of mint leaves extract. The juice was aseptically processed, packed in glass bottles under sterilized environment and sterilized at 70°C for 15min then storage at 5°C for 3 months. All of the properties of juice "physicochemical, nutritional values, microbiological and sensory" was determined.
Results:
The results showed that there was no difference in pH, total soluble solids, ash, and total acidity in all samples moreover, the orange juice with 15% of mint leaves extract recorded the best values of sensory evaluation, on the other hand, it was recorded lower values of vitamin C and total phenolic compound than fresh or pasteurized orange juice because of increasing in addition % of mint leaves extract to orange juice. The sensory properties of juice samples were not remarkable any changes during storage. The results indicated that the juice had a good acceptability up to 3 months of storage at 5°C.
Conclusion:
Now, the consumer is interested with nutritional and healthy foods, because functional foods reduce the health problems, as described in various patents. So, the Orange-Mint leaves blended juice will be a good option for the consumer.
... Studies have suggested that extreme nutritional factors usually induce insulin resistance (IR) [22,23]. Alloxan, a classical diabetogen, can be selectively toxic to the pancreatic beta cells through oxidative stress-related DNA damage in the sensitive cells. ...
To determine whether treatment with ginseng oligopeptides (GOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in rats induced by high-fat diet and low doses of alloxan, type 2 diabetes was induced in male Sprague-Dawley (SD) rats by injecting them once with 105 mg/kg alloxan and feeding them high-carbohydrate/high-fat diet with or without GOP administration (0.125, 0.5, and 2.0 g/kg Body Weight) for 7, 24, and 52 weeks. Oral glucose test tolerance (OGTT), plasma glucose, serum insulin, level of antioxidant, and beta cell function were measured. Morphological observation and immunohistochemistry study of insulin of islets was performed by light microscopy. The insulin level and the expression of NF-κB and Bcl-2 family in pancreatic islets were also detected by Western blot analysis. In addition, survival time and survival rate were observed. After the treatment, the abnormal OGTT were partially reversed by GOPs treatment in diabetic rats. The efficacy of GOPs was manifested in the amelioration of pancreatic damage, as determined by microscopy analysis. Moreover, GOPs treatment increased the normal insulin content and decreased the expression of the NF-κB-signaling pathway. Compared with those in the control model, the survival time and rate were significantly longer. It is suggested that GOPs exhibit auxiliary therapeutic potential for diabetes.
... Accordingly, dealcoholized red wine as well as an important flavanol found in GP, (-)-epicatechin was able to ameliorate fructose induced biochemical modifications in the heart through modulating the expression and/or activity of Nox and eNOS and thus favoring NO bioavailability 28,40 . Chronic consumption of grape phenolics improved oxidative stress markers by preventing in part NAD(P)H oxidase expression in left cardiac ventricle on high-fat diet-induced obesity hamsters 41 . ...
Metabolic syndrome (MetS) is a risk factor of sudden cardiac death in humans but, animal models for the study of this association are needed. Grape pomace (GP), obtained from winemaking process, contains phenolic compounds with potential cardioprotective effects. The aim of this study was to evaluate if a high-fat-fructose (HFF) diet facilitates the occurrence of arrhythmias during the reperfusion, and if a GP supplementation could counteracts this effects. Wistar rats were fed with control (Ctrl), HFF diet and HFF plus GP (1g/Kg/day) during six weeks. HFF diet induces characteristic features of MetS (higher systolic blood pressure, dyslipidemia and insulin resistance) which was attenuated by GP supplementation. In addition, HFF induced increased reperfusion arrhythmias that were reduced upon GP supplementation. GP also reduced the non-phosphorylated form of connexin-43 (Cx43) while enhances heart p-AKT and p-eNOS protein levels and reduces Nox4 levels enhanced by a HFF diet, indicating that GP may increase NO bioavailability in heart. We found a murine model of MetS with increased arrhythmogenesis and translational value. Furthermore, GP prevents diet-induced heart dysfunction and metabolic alterations. These results highlight the potential utilization of winemaking by-products containing important amount of bioactive compounds to prevent/attenuate MetS-associated cardiovascular pathologies.
... Low dose (25mg per kg body weight per day) GSPE treatment of high-fat-diet (HFD) fed rats significantly reduced the adiposity index and the weight of all the white adipose tissue depots and reversed the increase in plasma phospholipids induced by the HFD feeding (Caimari et al., 2012). Chronic consumption of grape phenolics has been shown to reduce obesity development and related metabolic pathways including adipokine secretion and oxidative stress in a rat model (Décordé et al., 2009). Cancer chemopreventive and anticancer efficacy of grape seed extract and other grapebased products were summarized by Kaur et al., (2009). ...
Grape pomace (GP) is a by-product of wine industry, in which remains significant amount of polyphenols. The freshly pressed pomace is perishable and has to be dried for use at later time. Depending on the drying methods, significant loss in polyphenols may occur during drying. This chapter describes the impacts of dehydration methods such as room temperature drying and vacuum drying on the retention of polyphenols in the pomace of Cabernet Sauvignon and Muscadine Nobel grapes using freeze dried sample as control. Seeds, skins and stems were separated manually after drying and the effects of drying methods on the stability of GP polyphenols were evaluated by the retentions of total polyphenol (TP), total anthocyanins (TA) and total flavonoids (TF). Results show that seeds and stems from both grape varieties were rich in TP and TF but low in TA, while skins were rich in anthocynin. Compared to freeze drying, both room temperature and vacuum oven drying methods resulted in significant loss of TP, TA and TF in different parts of Muscadine pomace. Among different groups of polyphenols, anthocyanin was affected the most by drying methods. Flavonoids in Cabernet pomace exhibited higher heat stability than that in Muscadine pomace indicating the differences in flavonoid composition between the two grape varieties. Therefore, the polyphenol composition and stability of GP are variety dependent. The selection of drying method needs to consider what type of polyphenol to be preserved, variety of GP and the cost of drying method.
... Grape seed extract prevented in part the increase on plasma glucose, triglycerides, insulin and insulin resistance, lowering insulinemia and leptinemia. Oxidative stress, assessed by cardiac production of superoxide anion and NAD(P)H oxidase expression, was reduced [42]. Grape seed proanthocyanidin rich extracts dose and time dependently prevented tert-butylhydroperoxide-induced oxidative stress in two intestinal cell types: the absorptive cell line Caco-2 and the enteroendocrine cell line STC-1. ...
Grapes, grape products and by-products represent a widely distributed and studied source of natural antioxidants, which also show health benefits in relation to cardiovascular and degenerative diseases. Grape seeds are part of the wine industry byproducts and the valorization of their constituents has interest. The present chapter reviews the composition of grape seeds, particularly the phenolic profile, the different extraction methodologies reported for the extraction of phenolic compounds for production of antioxidant extracts and the antioxidant capacities evaluated by different protocols.
... High nutrient intake in IUGR piglets led to abnormal immune function during the suckling period by lowering serum concentrations of cytokines such as TNF and IL-1β. Moreover, intense nutrient intake induces excessive oxidative stress (87)(88)(89) , which can impose a further burden on the immature antioxidant system in LBW offspring (90)(91)(92) . ...
Infants born with low birth weights (<2500 g, LBW), accounting for about 15 % of newborns, have a high risk for postnatal growth failure and developing the metabolic syndromes such as type 2 diabetes, CVD and obesity later in life. Improper nutrition provision during critical stages, such as undernutrition during the fetal period or overnutrition during the neonatal period, has been an important mediator of these metabolic diseases. Considering the specific physiological status of LBW infants, nutritional intervention and optimisation during early life merit further attention. In this review, the physiological and metabolic defects of LBW infants were summarised from a nutritional perspective. Available strategies for nutritional interventions and optimisation of LBW infants, including patterns of nutrition supply, macronutrient proportion, supplementation of amino acids and their derivatives, fatty acids, nucleotides, vitamins, minerals as well as hormone and microbiota manipulators, were reviewed with an aim to provide new insights into the advancements of formulas and human-milk fortifiers.
... Obesity and diabetes are other underlying factors linked to metabolic and cardiovascular risk [39,40], as well as abnormal cortisol levels and metabolism [41][42][43]. ...
Abstract: Oxidative stress is exacerbated in overweight and obese individuals after acute exercise compared with their non-obese counterparts. Antioxidant supplementation of the diet may be one intervention to reduce exercise-induced oxidative stress in this vulnerable population. The aim of this study was to investigate whether polyphenol-rich pomegranate juice attenuates post-exercise oxidative stress and contributors to oxidative stress (glucocorticoids) and blood pressure in healthy overweight subjects.
Methods: Males and females participated in a randomized placebo controlled parallel pilot-study (mean BMI: 26.7 ± 6.6 kg/m2). Two groups of (n = 12) participants received either pomegranate pure juice (500 mL/day containing 1685 mg GAE/L) total phenolics) or placebo (matched for total energy and volume) and all participants completed two standardized 30 min treadmill tests (50% Wmax) at baseline and after one week of treatment.
Results: Exercise induced lipid peroxidation (MDA) was decreased following pomegranate juice consumption compared with placebo (31.2 ± 10.6 to 26.5 ± 9.8 MDA μmole/day) after 1 week (P = 0.035). Urinary free cortisol was reduced from 179.4 ± 53.2 to 125.6 ± 43.5 nmole/24h (p = 0.042). In addition, there was an increase in urinary free cortisone: 112.2 ± 40.4 to 187.6 ± 90.2 nmole/24 h (p = 0.045), and a decrease in the urinary free cortisol/cortisone ratio (p=0.009) from 1.6 ± 1.1 to 0.67 ± 0.55 following one week of pomegranate juice intake. Pomegranate juice consumption was also found to lower systolic blood pressure pre-exercise (136.7 ± 11.7 to 131.8 ± 8.8 mmHg (p=0.007), and post-exercise from 158.8 ± 15.8 to 148.1 ± 12.3 mmHg (p < 0.01) and diastolic blood pressure (86.3 ± 10.6 to 82.5 ± 6.8 mmHg (p = 0.04) and 103.1 ± 12.5 to 93.9 ± 11.5 mmHg (p = 0.001), pre and post exercise, respectively. Correlation results between the change in Cortisol/cortisone ratio with the effect on blood pressure showed a negative significant association post pomegranate juice intake (p = 0.028 for systolic and p = 0,008 for diastolic BP). There were no changes in lipid peroxidation or blood pressure following placebo treatment.
Conclusions: These findings suggest that pomegranate juice consumption prior to an acute bout of moderate intensity exercise reduces blood pressure and exercise-induced oxidative stress in the overweight and obese population.
Keywords: Pomegranate juice; Blood Pressure; Glucocorticoids; Exercise; Oxidative Stress
... Obesity and diabetes are other underlying factors linked to metabolic and cardiovascular risk [39,40], as well as abnormal cortisol levels and metabolism [41][42][43]. ...
Abstract
Background: Oxidative stress is exacerbated in overweight and obese individuals after acute exercise compared with their non-obese counterparts. Antioxidant supplementation of the diet may be one intervention to reduce exercise-induced oxidative stress in this vulnerable population. The aim of this study was to investigate whether polyphenol-rich pomegranate juice attenuates post-exercise oxidative stress and contributors to oxidative stress (glucocorticoids) and blood pressure in healthy overweight subjects.
Method: Males and females participated in a randomized placebo controlled parallel pilot-study (mean BMI: 26.7 ± 6.6 kg/m2). Two groups of (n = 12) participants received either pomegranate pure juice (500 mL/day containing total polyphenols of 1685 mg GAE/L) or placebo (water matched for total energy) and all participants completed two standardized 30 min treadmill tests (50% Wmax) at baseline and after one week of the intervention.
Results: Exercise induced lipid peroxidation (MDA) was lower following pomegranate juice consumption compared with placebo (31.2 ± 10.6 to 26.5 ± 9.8 MDA μmole/day) after 1 week (P = 0.035). Urinary free cortisol was reduced from 179.4 ± 53.2 to 125.6 ± 43.5 nmole/24h which was significant (p = 0.042). In addition, there was a statistically significant increase in urinary free cortisone: from 112.2 ± 40.4 to 187.6 ± 90.2 nmole/24 h (p = 0.045), and a significant decrease in the urinary free cortisol/cortisone ratio (p=0.009) from 1.6 ± 1.1 to 0.67 ± 0.55 following one week of pomegranate juice intake. Pomegranate juice consumption was also found to decrease systolic blood pressure pre-exercise (136.7 ± 11.7 to 131.8 ± 8.8 mmHg (p=0.007), and post-exercise from 158.8 ± 15.8 to 148.1 ± 12.3 mmHg (p < 0.01) and diastolic blood pressure (86.3 ± 10.6 to 82.5 ± 6.8 mmHg (p = 0.04) and 103.1 ± 12.5 to 93.9 ± 11.5 mmHg (p = 0.001), pre and post exercise, respectively. Correlation results between the change in Cortisol/cortisone ratio with the effect on blood pressure showed a negative significant association post pomegranate juice intake (p = 0.028 for systolic and p = 0,008 for diastolic BP). There were no changes in lipid peroxidation or blood pressure following placebo treatment.
Conclusions: These findings suggest that pomegranate juice consumption prior to an acute bout of moderate intensity exercise may alleviate blood pressure and exercise-induced oxidative stress in the overweight and obese population.
Keywords: Pomegranate juice; Blood Pressure; Glucocorticoids; Exercise; Oxidative Stress
... Rutin also inhibited the expression of leptin and then up-regulated the expression of adiponectin at the protein level in 3T3-L1 adipocytes (Hsu et al., 2009). Moreover, oxidative stress could be also related to adipokine imbalance (Décordé et al., 2009). Therefore, the inhibition of TNF-α secretion and the increase of adiponectin secretion and leptin sensitivity related to antioxidant effects may improve obesity through inhibition of inflammation, improvement of insulin resistance (Kadowaki et al., 2006;Ye, 2013), or correctness for imbalance between food intake and energy expenditure (Jung & Choi, 2014) . ...
Rutin, a phenolic compound, has antioxidant, anti-dyslipidaemic, and body weight-reducing effects. We evaluated the anti-arteriosclerotic, antioxidant, and body weight-reducing effects of rutin-rich Tartary buckwheat. We randomly divided 144 adult subjects into an active test food group consuming products containing rutin-rich Tartary buckwheat and a placebo food group. Body composition measurements and haematological and urine tests were performed at weeks 0, 4, 8, and 12, and at 3 weeks after termination. Atherosclerosis index and ox-LDL did not significantly differ between the groups. However, TBARS levels, BW and BMI in the active test food group were significantly lower than those in the placebo group at week 8 (p = 0.027, p = 0.030, respectively). BFP in the active test food group at week 4 (p = 0.038) was lower than that in the placebo group. Thus, rutin-rich Tartary buckwheat intake may be effective for body weight due to its antioxidant properties.
Background
Progressive, involuntary weight and lean mass loss in cancer are linked to cachexia, a prevalent syndrome in gastrointestinal malignancies that impacts quality of life, survival and postoperative complications. Its pathophysiology is complex and believed to involve proinflammatory cytokine-mediated systemic inflammation resulting from tumor-host interaction, oxidative stress, abnormal metabolism and neuroendocrine changes. Therapeutic options for cachexia remain extremely limited, highlighting the need for clinical research targeting new interventions. Thus, this study primarily assesses the effects of grape-seed flour (GSF), rich in polyphenols and fibers, for attenuating perioperative weight loss in colorectal cancer.
Methods
This is a dual-center, triple-masked, placebo-controlled, parallel-group, phase II, randomized clinical trial designed to investigate GSF supplementation in subjects with pre- or cachexia associated with colorectal cancer during the perioperative period. Eighty-two participants will receive 8g of GSF or cornstarch (control) for 8 weeks. Assessments are scheduled around surgery: pre-intervention (4 weeks prior), day before, first week after, and post-intervention (4 weeks later). The primary endpoint is the difference in body weight mean change from baseline to week 8. The secondary endpoints describe the harms from 8-week supplementation and assess its superiority to improve body composition, post-surgical complications, quality of life, anorexia, fatigue, gastrointestinal symptoms, and handgrip strength. The study will also explore its effects on gut bacteria activity and composition, systemic inflammation, and muscle metabolism.
Discussion
The current trial addresses a gap within the field of cancer cachexia, specifically focusing on the potential role of a nutritional intervention during the acute treatment phase. GSF is expected to modulate inflammation and oxidative stress, both involved in muscle and intestinal dysfunction. The research findings hold substantial implications for enhancing the understanding about cachexia pathophysiology and may offer a new clinical approach to managing cachexia at a critical point in treatment, directly impacting clinical outcomes.
Trial registration
The Brazilian Registry of Clinical Trials (ReBEC), RBR-5p6nv8b; UTN: U1111-1285-9594. Prospectively registered on February 07, 2023.
Procyanidin (PC) is a polyphenolic compound with antioxidant activity. The purpose of this study was to determine the influence of PC on canine sperm quality after 72 h of storage at 4 °C. The collected ejaculates were separated into four equal aliquots and treated with various concentrations of PC (0, 10, 30, and 50 μg/mL) in Tris-citric-fructose-egg yolk (TCFE) extender and stored at 4 °C for 72 h. The findings revealed that 30 μg/mL PC was the optimum concentration for significantly improving sperm motility (p < 0.05). Sperm samples treated with 30 μg/mL PC had substantially greater plasma membrane integrity, acrosome integrity, and mitochondrial membrane potential than the control group (p < 0.05). Furthermore, T-AOC and the expression levels of superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx1) genes were significantly higher in sperm treated with 30 μg/mL PC than those in control (p < 0.05). In summary, this study discovered that adding PC to the TCFE extender enhanced sperm quality and that 30 μg/mL PC was the optimal concentration for canine sperm when stored at 4 °C.
Increased oxidative stress has been linked to the pathogenic process of obesity and can trigger inflammation, which is often linked with the risk factors that make up metabolic syndrome (MetS), including obesity, insulin resistance, dyslipidaemia and hypertension. TetraSOD®, a natural marine vegan ingredient derived from the microalgae Tetraselmis chuii that is high in the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) has recently demonstrated in vitro increased activity of these key antioxidant enzymes. In the present study, the potential bioactive effects of three dietary dosages of TetraSOD® in enhancing antioxidant and anti-inflammatory mechanisms to combat the metabolic disturbances that compose MetS were assessed in rats given a cafeteria (CAF) diet. Chronic supplementation with 0.17, 1.7, and 17 mg kg−1 day−1 of TetraSOD® for 8 weeks ameliorated the abnormalities associated with MetS, including oxidative stress and inflammation, promoting endogenous antioxidant defence mechanisms in the liver (GPx and GSH), modulating oxidative stress and inflammatory markers in plasma (NOx, oxLDL and IL-10), and regulating genes involved in antioxidant, anti-inflammatory and immunomodulatory pathways in the liver, mesenteric white adipose tissue (MWAT), thymus, and spleen. Overall, TetraSOD® appears to be a potential therapeutic option for the management of MetS.
While the underlying mechanism remains unknown, Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu or Rubus suavissimus S. Lee (RS), a sweet plant distributed in southwest of China, has been used as beverage and folk medicine. Pharmacological studies indicated the potential of RS improving the obesity phenotype and hyperlipidemia. The mechanism is still not yet to be put forward. To verify the substantial effects of RS on lipid metabolism, a Syrian golden hamster model was adopted. The physiological and pathological evaluation of experimental animals demonstrated that RS can relieve the lipid metabolism disorder induced by high-fat diet and alleviated liver injury. RS upregulation the expressions of peroxisome proliferator-activated receptor α (PPARα), PPARγ and CCAAT/enhancer binding protein α (C/EBPα), as well as adipocyte-specific genes, glucose transporter 4 (Glut4), lipoprotein lipase (LPL) and fatty acid binding protein 4 (aP2). On the other side, RS suppressed the sterol regulatory element binding protein 1 (SREBP1) and downstream acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase-1 (SCD1) and fatty acid synthase (FAS). In conclusion, RS alleviated lipid metabolism disorder symptoms caused by high-fat diet accompanied with 8 weeks of treatment, involving enhanced β-oxidation, increased adipogenesis and decreased the metabolism of fatty acids, via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.
Black soybean (Glycine max L), a cultivar containing abundant polyphenols in its seed coat such as anthocyanins and flavan-3-ols, has been reported to possess various health benefits toward lifestyle diseases. In this review article, the safety evaluation of polyphenol-rich black soybean seed coat extract (BE), and absorption of BE polyphenols are summarized. Additionally, we describe the antioxidant activity of BE polyphenols and their ability to induce antioxidant enzymes. The health benefits of BE and its polyphenols, such as its anti-obesity and anti-hyperglycemic activities through the activation of AMP-activated protein kinase and translocation of glucose transporter 4, respectively, are also discussed. Furthermore, we identified the improvement of vascular function by BE. These emerging data require further investigation in scientific studies and human trials to evaluate the prevention of lifestyle diseases using black soybean polyphenols.
Juicing of grapes includes contact with phenolic rich seeds and skins that otherwise rely on mastication for phenolic release. To understand if 100% grape juice can provide a matrix with highly bioaccessible phenolics relative to whole fruit, differences in phenolic content and bioaccessibility from commonly consumed table, Concord (CG) and Niagara (NG) grapes and their 100% juices were compared. Phenolic content in whole grapes and 100% juices were assayed by LC-MS prior to in vitro digestion to determine phenolic bioaccessibility. Phenolic compounds were concentrated in CG and NG seeds as flavan-3-ols (222.2 – 285.5 mg/100g fw). CG skins were rich in anthocyanins (201.4 mg/100g fw) and flavonols (15.5 mg/100g fw). Product form had a significant impact on content (p < 0.01), relative bioaccessibility, and absolute bioaccessibility (p < 0.01). CG had a higher total phenolic content (21.9 - 50.7 mg/100g fw) compared to CGJ (5.8 mg/100g fw), though NG (4.9 - 10.8 mg/100g fw) was similar in phenolic content to NGJ (9.4 - 10.8 mg/100g fw). Absolute bioaccessibility of total phenolics from CGJ (5.2 mg/100g fw) was similar to CG (2.6 - 9.6 mg/100g fw), while NGJ (5.1 - 5.7 mg/100g fw) had higher bioaccessible phenolic content than NG (0.8 – 1.1 mg/100g fw). Differences in bioaccessible content were driven by high relative bioaccessibility of anthocyanins in CGJ (86-135%) compared to CG (14-39%) as well as for flavan-3-ols and phenolic acids from CGJ/NGJ (48-101; 39-85%) compared to CG/NG (0-3; 9-67%). Comparisons between juices and table grapes followed similar trends. A greater fraction of skin and seed phenolics were extracted through juicing and made bioaccessible making 100% grape juice and whole fruit similar in phenolic delivery to consumers.
Ethnopharmacological relevance:
Alibertia edulis (L.C. Rich.) A.C. Rich is a vegetable species used in Brazilian folk medicine due to it is putative hypoglycemiant effect but has never been pharmacologically investigated. It is popularly used for the control of diabetes, especially in the state of Mato Grosso, Brazil. Following confirmation of the antioxidant activity of A. edulis by Aquino et al. (2017), the aim of this study was to evaluate the effects of leaves of A. edulis aqueous extract (AEAE) on some biochemical parameters in mice fed a high-fat fed.
Material and methods:
Leaves of A. edulis were air-dried in an oven at 40 °C for 10 days and ground into a fine powder by mechanical milling. The AEAE was prepared by decoction (1:10 w/v) at 97 °C for 15 min, and later filtered and lyophilized. Preliminary phytochemical analysis of the AEAE has been already indetified the presence of caffeic acid, quercetin 3-rhamnosyl-(1 → 6)-galactoside and iridois ioxide, ferulic acid and rutin in decocted leaves (Aquino et al., 2017). In one experiment, the acute oral toxicity AEAE was evaluated at 2,000 mg/kg of body weight. The animals were observed periodically for 14 days. In second experiment, the animals were divided into four groups (n = 5): Control, AEAE 200, AEAE 400 mg/kg and positive control (Metformin 100 mg/kg). In a third experiment, animals were divided into: Control RC (standard diet) (n = 24) and Control HFF (high-fat fed) (n = 24) groups for induction of glucose intolerance. After eight weeks, they were further subdivided into six groups (n = 8 each) RC or HFF with or without AEAE at doses of 200 and 400 mg/kg (2-wk) treatments to assess glucose tolerance. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and expression of the antioxidant proteins of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and phosphorylated IKK were determined.
Results:
The HF-fed animals developed glucose intolerance which the AEAE failed to revert. Meanwhile, the AEAE treatment did lower the glucose levels in the normolipidic cohorts by virtue of its antioxidant property. It was also observed that the treatment with the AEAE reduced food intake negatively interfering weight accretion. Beyond that, the treatment with AEAE interfered in the SOD and catalase expression and inhibited phosphorylation of IKK thus suggesting that the observed hypoglycemiant power may be related to its known antioxidant potential. No sings of toxicity or hemolysis were detectaed at indicating that, at the concentrations evaluated, the extract was not toxic to normal cells.
Conclusion:
The AEAE showed a hypoglycemiant effect in the normolipidic mice that received the control diet, but not in those that were made glucose-intolerant by consuming a high-fat fed. The extract also exhibited substantial protection against hemolysis and oxidative stress. Moreover, no signs of toxicity were evident at 2000 mg/kg of body weight.
Lotus seed epicarp (LSE) and lotus seed pot (LSP) were characterized and a total of 5 and 7 proanthocyanidins (PAs) were identified in purified LSE and LSP extract, respectively. Purified LSE and LSP PAs significantly suppressed the body weight and weight gain of white adipose tissue (WAT) and decreased the WAT cell size in high-fat diet induced obese mice regardless of the daily food intake. LSE or LSP administration significantly lowered the serum leptin level and improved the serum and liver lipid profiles (including TC, TG, HDL-C, LDL-C levels), increased activities of antioxidant enzymes (SOD, GST) and GSH concentration, and suppressed lipid peroxidation in hepatic tissue. LSP PAs was generally more effective than LSE PAs. Both extracts ameliorated obesity, insulin resistance and oxidative damage in obese mice, suggesting they are good candidates for value-added functional food and nutraceutical ingredients.
To elucidate the possible mechanisms for the preventive effect of procyanidin B2 on aging, a combined analysis of metabolic profile and gut microbiome was carried out in the present study. The mimetic aged mice induced by d-galactose injection (500 mg/kg, sc daily), and the preventive group was fed with the diet plus 0.2% procyanidin B2. After 7 weeks of treatment, the spatial memory was assayed using the Morris water maze test. Procyanidin B2 significantly ameliorated the impaired memory and antioxidant abilities induced by d-galactose. Furthermore, metabolomics analysis of plasma based on LC/Q-TOF-MS demonstrated that phosphatidyl cholines, oleic acid, linoleic acid, carnitine, pantothenic acid, and taurocholic acid were significantly increased in the mice treated with procyanidin B2, and pyruvic acid, hydroxybutyric acid, hippuric acid, and cholic acid were decreased significantly. Together, gut microbiome analysis using Illumina sequencing showed that there were significant differences in the Firmicutes/Bacteroidetes ratio and abundance of Roseburia, Lachnospiraceae, and Bifidobacterium between the aging and supplemental procyanidin B2 groups. In summary, procyanidin B2 possessed potential prevention of the cognitive and oxidative impairment via the metabolic pathway regulation related to glycolysis, fatty acid, and bile acid in the aged mice, accompanied by remodeling the gut flora.
Les effets du GSSE (Grape seed and skin extract), extrait de raisin particulièrement riche en antioxydants, ont été étudiés pour prévenir les troubles métaboliques et cardiovasculaires liés à l’obésité. L’obésité est caractérisée par une accumulation ectopique de graisse dans les tissus non adipeux tels que le cerveau. Cette lipotoxicité cérébrale induit une inflammation chronique au niveau du cerveau. Dans ce présent travail, nous avons décrit l’effet anti-obésité du GSSE dans un modèle expérimental d’obésité induite par un régime alimentaire à haute teneur en graisses (HFD) tout en mettant l’accent sur le stress oxydant ainsi que le dysfonctionnement métabolique du cerveau qui n’est pas organe cible de l’obésité. Grâce à ce travail, nous avons développé une approche protéomique quantitative Nano LCMS/MS Label free afin d’identifier les biomarqueurs liés au traitement riche en lipides (HFD) et à la protection apportée au cerveau par le GSSE. Pour ce faire, on a eu recours à un modèle animal afin de mieux comprendre les voies métaboliques potentielles altérées par l’obésité et la protection apportée par le GSSE. Plusieurs protéines ont été identifiées et quantifiées en comparant le protéome cérébral total chez les rats dans les différentes conditions de traitements. On a eu recours à des outils de bioinformatique qui nous ont permis de conclure que ces protéines significativement différenciées sont principalement liées à la voie de la phosphorylation oxydative, de la glycolyse / néoglucogenèse et celle de la signalisation du calcium. Ces résultats ont été confirmés par la mesure de quelques activités enzymatiques métaboliques. Fait intéressant, qu’elles soient sous ou surexprimées par le traitement du HFD, le GSSE corrige l’effet délétère apporté aux différentes protéines et enzymes suite au traitement du HFD. D’autres voies métaboliques cérébrales ont été induites par le GSSE telle que le « HIF signaling pathway ». Ces résultats nous permettent de fournir un élan pour l’investigation thérapeutique du GSSE contre différents désordres métaboliques.
Scope:
Consumption of products rich in flavan-3-ols, such as tea and cocoa, has been associated with decreased obesity, partially dependent on their capacity to enhance energy expenditure. Despite these phenolics having been reported to increase the thermogenic program in brown and white adipose tissue, flavan-3-ols are vastly metabolised in vivo to phenyl-γ-valerolactones. Therefore, we hypothesize that phenyl-γ-valerolactones may directly stimulate the differentiation and the activation of brown adipocytes.
Methods and results:
Immortalized brown pre-adipocytes were differentiated in presence of (R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL1), (R)-5-(3'-hydroxyphenyl)-γ-valerolactone-4'-O-sulphate (VL2), (R)-5-phenyl-γ-valerolactone-3',4'-di-O-sulphate (VL3), at concentrations of 2 or 10μM, whereas fully differentiated brown adipocyte were treated acutely (6-24h). None of the treatments regulated the expression levels of the uncouple protein 1, nor of the main transcription factors involved in brown adipogenesis. Similarly, mitochondrial content was unchanged after treatments. Moreover these compounds did not display peroxisome proliferator-activated receptor γ-agonist activity, as evaluated by luciferase assay, and did not enhance norepinephrine-stimulated lipolysis in mature adipocytes. However, both VL1 and VL2 prevented oxidative stress caused by H2 O2 .
Conclusion:
Phenyl-γ-valerolactones and their sulphated forms do not influence brown adipocyte development or function at physiological or supraphysiological doses in vitro, but they are active protecting brown adipocytes from increased reactive oxygen species production. This article is protected by copyright. All rights reserved.
Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.
A large national cohort of children studied from birth to 36 years was used to test the predictive value of childhood obesity for obesity in adult life. Only 21% (39) of obese 36 year olds had been obese at age 11 years, and even when associated social factors were taken into account the correctly predicted percentage was much lower than the prediction rate achieved using body mass data from age 26 years. The comparatively poor predictive value of childhood obesity and the association of adult obesity with educational achievements and socioeconomic circumstances of family of origin emphasise the need for encouraging good nutritional and exercise habits rather than placing undue emphasis on the control of childhood obesity.
Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans.
In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity.
We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men (r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27 kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive ( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63).
We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity
Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.
Leptin, a protein encoded by the obese gene, is produced by adipocytes and released into the bloodstream. In obese humans, serum leptin levels are increased and correlate with the individual's body mass index and blood pressure. Elevated serum concentrations of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, were also observed in obese subjects. The pathomechanisms underlying this ET-1 increase in obesity are poorly understood. In the present study, we investigated the influence of the ob gene product leptin on the expression of ET-1 in human umbilical vein endothelial cells (HUVECs). Binding studies using (125)I-radiolabeled leptin revealed high- and low-affinity leptin binding sites on HUVECs (Kd1=13.1+/-3.1 nmol/L and Kd2=1390+/-198 nmol/L, respectively), mediating a time- and dose-dependent increase of ET-1 mRNA expression and protein secretion after incubation of HUVECs with leptin. This leptin-induced ET-1 expression was inhibited by preincubation of HUVECs with 0.75 micromol/L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob-Rb. Furthermore, after incubation with leptin, increased nuclear staining of c-fos and c-jun, the major components of the transcription factor AP-1, and increased AP-1 DNA binding were observed. Transient transfection studies with ET-1 promoter constructs showed that leptin-induced promoter activity was abolished in the absence of AP-1 binding sites or by cotransfection with a plasmid overexpressing a mutated jun, which is able to bind c-fos but not DNA. Thus, leptin upregulates ET-1 production in HUVECs via a mechanism potentially involving jun binding members of the bZIP family.
Obesity and diabetes are increasing in the United States.
To estimate the prevalence of obesity and diabetes among US adults in 2001.
Random-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001.
Body mass index, based on self-reported weight and height and self-reported diabetes.
In 2001 the prevalence of obesity (BMI > or =30) was 20.9% vs 19.8% in 2000, an increase of 5.6%. The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an increase of 8.2%. The prevalence of BMI of 40 or higher in 2001 was 2.3%. Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status. Compared with adults with normal weight, adults with a BMI of 40 or higher had an odds ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50) for diagnosed diabetes, 6.38 (95% CI, 5.67-7.17) for high blood pressure, 1.88 (95% CI,1.67-2.13) for high cholesterol levels, 2.72 (95% CI, 2.38-3.12) for asthma, 4.41 (95% CI, 3.91-4.97) for arthritis, and 4.19 (95% CI, 3.68-4.76) for fair or poor health.
Increases in obesity and diabetes among US adults continue in both sexes, all ages, all races, all educational levels, and all smoking levels. Obesity is strongly associated with several major health risk factors.
Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue.
To determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance.
Randomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy.
One hundred twenty premenopausal obese women (body mass index > or =30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia.
The 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise.
Lipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin.
After 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P<.001), monounsaturated fat (2%; P =.009), and fiber (7 g/d; P<.001); had a lower ratio of omega-6 to omega-3 fatty acids (-5; P<.001); and had lower energy (-310 kcal/d; P<.001), saturated fat (-3.5%; P =.007), and cholesterol intake (-92 mg/d; P<.001) than controls. Body mass index decreased more in the intervention group than in controls (-4.2; P<.001), as did serum concentrations of IL-6 (-1.1 pg/mL; P =.009), IL-18 (-57 pg/mL; P =.02), and CRP (-1.6 mg/L; P =.008), while adiponectin levels increased significantly (2.2 microg/mL; P =.01). In multivariate analyses, changes in free fatty acids (P =.008), IL-6 (P =.02), and adiponectin (P =.007) levels were independently associated with changes in insulin sensitivity.
In this study, a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.
To examine the antiobesity effect of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol in a mouse model of diet-induced obesity.
Obesity was induced in male New Zealand black mice by feeding of a high-fat diet. EGCG purified from green tea (TEAVIGO) was supplemented in the diet (0.5 and 1%). Body composition (quantitative magnetic resonance), food intake, and food digestibility were recorded over a 4-week period. Animals were killed and mRNA levels of uncoupling proteins (UCP1-3), leptin, malic enzyme (ME), stearoyl-CoA desaturase-1 (SCD1), glucokinase (GK), and pyruvate kinase (PK) were analysed in different tissues. Also investigated were acute effects of orally administered EGCG (500 mg/kg) on body temperature, activity (transponders), and energy expenditure (indirect calorimetry).
Dietary supplementation of EGCG resulted in a dose-dependent attenuation of body fat accumulation. Food intake was not affected but faeces energy content was slightly increased by EGCG, indicating a reduced food digestibility and thus reduced long-term energy absorption. Leptin and SCD1 gene expression in white fat was reduced but SCD1 and UCP1 expression in brown fat was not changed. In liver, gene expression of SCD1, ME, and GK was reduced and that of UCP2 increased. Acute oral administration of EGCG over 3 days had no effect on body temperature, activity, and energy expenditure, whereas respiratory quotient during night (activity phase) was decreased, supportive of a decreased lipogenesis and increased fat oxidation.
Dietary EGCG attenuated diet-induced body fat accretion in mice. EGCG apparently promoted fat oxidation, but its fat-reducing effect could be entirely explained by its effect in reducing diet digestibility.
Renal oxygen tension is substantially lower in the medulla than in the cortex and is reduced in hypertensive rats, a model of oxidative stress. Expression of NADPH oxidase, the primary source for superoxide anion (O(2)(-)*) in the kidney, is elevated in hypertension. Because molecular oxygen (O(2)) is required for O(2)(-)* formation, we tested the hypothesis that renal NADPH oxidase activity is limited by low O(2). O(2)(-)* production by rat kidney tissue or cultured cells exposed to levels of Po(2) that mimics those in the kidney was assessed by lucigenin-enhanced chemiluminescence. NADPH-dependent O(2)(-)* production by kidney homogenates decreased reversibly by 60-90% after graded reductions of ambient O(2) from 10 to 0% (76 to 2 mmHg Po(2)). The NADPH-dependent O(2)(-)* production by the kidney homogenate was reduced by decreasing Po(2) below approximately 30 mmHg. The response of tissue homogenates to low Po(2) was not different between normotensive and hypertensive rats. Similarly, NADPH-dependent O(2)(-)* production was lower during 2% O(2) compared with 10% O(2) in rat proximal tubule cells (-57 +/- 1%), vascular smooth muscle (-42 +/- 5%), cardiomyocytes (-57 +/- 1%), and mouse inner medulla collecting duct cells (-58 +/- 3%). We conclude that O(2)(-)* production by NADPH oxidase is dependent on availability of O(2). Therefore, O(2)(-)* generation may be limited in the kidney, both in the normal renal medulla and in the cortex of hypertensive kidneys.
Oxidative stress plays a critical role in the pathogenesis of atherosclerosis in patients with metabolic syndrome. This study aimed to investigate whether a relationship exists between phagocytic NADPH oxidase activity and oxidative stress and atherosclerosis in metabolic syndrome patients. The study was performed in 56 metabolic syndrome patients (metabolic syndrome group), 99 patients with one or two cardiovascular risk factors (cardiovascular risk factor group), and 28 healthy subjects (control group). NADPH oxidase expression and activity was augmented (P < 0.05) in metabolic syndrome compared with cardiovascular risk factor and control groups. Insulin was enhanced (P < 0.05) in metabolic syndrome patients compared with cardiovascular risk factor and control groups and correlated with NADPH oxidase activity in the overall population. Insulin stimulated NADPH oxidase activity; this effect was abolished by a specific protein kinase C inhibitor. Oxidized LDL and nitrotyrosine levels and carotid intima-media thickness were increased (P < 0.05) in the metabolic syndrome group compared with cardiovascular risk factor and control groups and correlated with NADPH oxidase activity in the overall population. These findings suggest that phagocytic NADPH oxidase overactivity is involved in oxidative stress and atherosclerosis in metabolic syndrome patients. Our findings also suggest that hyperinsulinemia may contribute to oxidative stress in metabolic syndrome patients through activation of NADPH oxidase.
Regular, moderate consumption of red wine is linked to a reduced risk of coronary heart disease and to lower overall mortality, but the relative contribution of wine's alcohol and polyphenol components to these effects is unclear. Here we identify procyanidins as the principal vasoactive polyphenols in red wine and show that they are present at higher concentrations in wines from areas of southwestern France and Sardinia, where traditional production methods ensure that these compounds are efficiently extracted during vinification. These regions also happen to be associated with increased longevity in the population.
Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.
Adiponectin-/- or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91(phox) protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin-/- mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin-/- than from wild-type mice (P<0.01). Moreover, myocardial ischemia/reperfusion-induced iNOS and gp91(phox) protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin-/- mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion-induced iNOS/gp91(phox) protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin-/- mice.
The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.
The acid concentration in the dimethylaminocinnamaldehyde (DC) reagent was reduced in order to give slower color development which allowed for more accurate assay of flavanols. The effect of water content in the sample on rate and total color development was shown. The method was used for estimation of degree of polymerization (DP) of isolated flavanols and flavanols in commercial wines of different ages. The apparent DP did not vary according to age of red wine except the youngest wine gave the lowest values. The ratio of flavonoids to DC values ranged from 3.24 to 3.89.
Leptin, a protein encoded by the obese gene, is produced by adipocytes and released into the bloodstream. In obese humans, serum leptin levels are increased and correlate with the individual’s body mass index and blood pressure. Elevated serum concentrations of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, were also observed in obese subjects. The pathomechanisms underlying this ET-1 increase in obesity are poorly understood. In the present study, we investigated the influence of the ob gene product leptin on the expression of ET-1 in human umbilical vein endothelial cells (HUVECs). Binding studies using 125I-radiolabeled leptin revealed high- and low-affinity leptin binding sites on HUVECs (Kd1=13.1±3.1 nmol/L and Kd2=1390±198 nmol/L, respectively), mediating a time- and dose-dependent increase of ET-1 mRNA expression and protein secretion after incubation of HUVECs with leptin. This leptin-induced ET-1 expression was inhibited by preincubation of HUVECs with 0.75 μmol/L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob-Rb. Furthermore, after incubation with leptin, increased nuclear staining of c-fos and c-jun, the major components of the transcription factor AP-1, and increased AP-1 DNA binding were observed. Transient transfection studies with ET-1 promoter constructs showed that leptin-induced promoter activity was abolished in the absence of AP-1 binding sites or by cotransfection with a plasmid overexpressing a mutated jun, which is able to bind c-fos but not DNA. Thus, leptin upregulates ET-1 production in HUVECs via a mechanism potentially involving jun binding members of the bZIP family.
French wines are abundant sources of phenolic compounds. The content of several catechins, i.e., (+)-catechin, (-)-epicatechin, dimers B1, B2, B3, and B4, trimers C1, and trimer 2 (T2), of 160 French wines was determined by HPLC with UV detection. Red wines (n = 95) were found to have high levels of catechins, ranging from 32.8 to 209.8 mg/L (mean concentration 114.5 mg/L) for (+)catechin, from 22.1 to 130.7 mg/L (mean concentration 75.7 mg/L) for (-)-epicatechin, from 7.8 to 39.1 mg/L (mean concentration 25.4 mg/L) for B1, from 18.3 to 93 mg/L (mean concentration 47.4 mgn) for B2, from 21.4 to 215.6 mg/L (mean concentration 119.6 mg/L) for B3, from 20.2 to 107.2 mg/L (mean concentration 81.9 mg/l) for B4, from 8.6 to 36.9 mg/L (mean concentration 26.3 mg/L) for C1, and from 26.7 to 79.3 mg/L (mean concentration 67.1 mg/L) for T2. White and rose wines (n. = 57 and n = 8) were found to have low levels of (+)-catechin (mean concentrations 9.8 and 10.6 mg/L, respectively) and (-)-epicatechin (mean concentrations 5.3 and 6.5 mg/L, respectively). These data provide a basis for the epidemiological evaluation of catechin intake by the consumption of French wine.
Procyanidin A from Aesculus hippocastanum differs from the B type procyanidin in that it is difficultly soluble in water, gives a higher yield of cyanidin when heated in butanolic HCl and the production of cyanidin continues beyond the 2 hr period sufficient for maximum production in the case of B type procyanidin. Anthocyanidin production and tannic acid equivalent (TAE) of extracts of species in which A and D type procyanidins have been reported to occur have been studied. Evidence of their presence was also found in Ribes laurifolium. Preparations of prodelphinidin from leaves of red currant and sainfoin had approximately twice the anthocyanidin production and the astringency of procyanidin B. Sources especially rich in prodelphinidin were a number of Ribes spp., Salix cinerea and Platanus acerifolia, from all of which the tannin was easily extracted. Some other species such as Pilea cadieri, although rich in prodelphinidin, are not suitable as sources because of the inextractability of the tannin.
Five tannin fractions were isolated from grape (Vitis vinifera) seeds. HPLC analysis of the degradation products released by thioacidolysis showed that all fractions consisted of catechin, epicatechin and epicatechin gallate units. Epicatechin was the major component in the extended chain. Catechin was more abundant in terminal units than in extension units. The proportion of galloyllated units varied from 13% to 29% as the Mr, increased. Mean degrees of polymerization ranging from 2.3 to 15.1 (by thiolysis) and from 2.4 to 16.7 (by GPC) were determined.
Insulin caused a transient increase in H2O2 accumulation in human fat cell suspensions that was observed only in the presence of an inhibitor of catalase and heme-containing peroxidases, such as azide, and reached peak levels of 30 microM within 5 min. The cells contained a plasma membrane-bound NADPH oxidase, producing 1 mol H2O2/mol of NADPH oxidation, that was activated on exposure of intact cells to insulin at contrations that are physiologically relevant (0.1-10 nM). The hormone effect was rapid and was due to a selective increase in substrate affinity. The enzyme was magnesium dependent, required a flavine nucleotide for optimal activity, and was most active at pH 5.0-6.5. In contrast to all other hormone- or cytokine-sensitive NADPH oxidases that have been characterized in sufficient detail, the human fat cell oxidase retained its hormone responsiveness after cell disruption, and only Mn2+, but no ATP, was required for a ligand-induced activation in crude plasma membranes. The results demonstrate that insulin utilizes tyrosine kinase-independent pathways for receptor signaling and strongly support the view that H2O2 contributes to the intracellular propagation of the insulin signal.
N epsilon-(carboxymethyl)lysine, N epsilon-(carboxymethyl)hydroxylysine, and the fluorescent cross-link pentosidine are formed by sequential glycation and oxidation reactions between reducing sugars and proteins. These compounds, termed glycoxidation products, accumulate in tissue collagen with age and at an accelerated rate in diabetes. Although glycoxidation products are present in only trace concentrations, even in diabetic collagen, studies on glycation and oxidation of model proteins in vitro suggest that these products are biomarkers of more extensive underlying glycative and oxidative damage to the protein. Possible sources of oxidative stress and damage to proteins in diabetes include free radicals generated by autoxidation reactions of sugars and sugar adducts to protein and by autoxidation of unsaturated lipids in plasma and membrane proteins. The oxidative stress may be amplified by a continuing cycle of metabolic stress, tissue damage, and cell death, leading to increased free radical production and compromised free radical inhibitory and scavenger systems, which further exacerbate the oxidative stress. Structural characterization of the cross-links and other products accumulating in collagen in diabetes is needed to gain a better understanding of the relationship between oxidative stress and the development of complications in diabetes. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.
Male hamsters were fed a hyperlipidemic diet consisting of standard chow supplemented with 3% cholesterol and 15% commercial butter for 12 months. In about 3 weeks serum total cholesterol doubled, raised 4-fold after the 4th week and after 10 months attained a 17-fold value. Low density lipoproteins (LDL)-cholesterol increased 4-fold after 4 weeks and about 13-fold after 10 months compared to control animals. In the first 2 weeks mononuclear cells began to adhere to the endothelium and a very intense stromal reaction appeared in the intima of the aortic arch. At the end of the 4th week of diet, Oil Red O stainable deposits were visible on the thoracic aorta, mostly on the arch, some of them as isolated, lipid-laden cells and others distributed on focal areas. Smooth muscle cells (SMC) appeared also in the intima of hyperlipidemic hamsters, compared to normal animals which had no macrophages or smooth muscle cells in the intima of the aortic specimens examined. Up to 6 months, smooth muscle cells in the intima and media began to load with lipids, as well as endothelial cells. After 10 months the affected zones looked like human atherosclerotic plaque with huge cholesterol crystal deposits, calcium deposits and necrosis. The endothelium, though very thinned and loaded with lipids, was morphologically intact.
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
Visceral obesity is frequently associated with muscle insulin resistance. Rats fed a high-fat diet rapidly develop obesity and insulin resistance. Dehydroepiandrosterone (DHEA) has been reported to protect against the development of obesity. This study tested the hypothesis that DHEA protects against the increase in visceral fat and the development of muscle insulin resistance induced by a high-fat diet in rats. Feeding rats a diet providing 50% of the energy as fat for 4 wk resulted in a twofold greater visceral fat mass and a 50% lower rate of maximally insulin-stimulated muscle 2-deoxyglucose (2-DG) uptake compared with controls. Rats fed the high-fat diet plus 0.3% DHEA were largely protected against the increase in visceral fat (+ 11.3 g in high fat vs. + 2.9 g in high fat plus DHEA, compared with controls) and against the decrease in insulin-stimulated muscle 2-DG uptake (0.94 +/- 0.15 mumol.ml-1.20 min-1, controls; 0.46 +/- 0.06 mumol.ml-1.20 min-1, high-fat diet; 0.78 +/- 0.07 mumol.ml-1.20 min-1, high fat + DHEA). DHEA did not affect food intake. These results show that DHEA has a protective effect against accumulation of visceral fat and development of muscle insulin resistance in rats fed a high-fat diet.
French wines are abundant sources of phenolic compounds. The content of several catechins, i.e., (+)-catechin, (-)-epicatechin, dimers B1, B2, B3, and B4, trimers C1, and trimer 2 (T2), of 160 French wines was determined by HPLC with UV detection. Red wines (n = 95) were found to have high levels of catechins, ranging from 32.8 to 209.8 mg/L (mean concentration 114.5 mg/L) for (+)-catechin, from 22.1 to 130.7 mg/L (mean concentration 75.7 mg/L) for (-)-epicatechin, from 7.8 to 39.1 mg/L (mean concentration 25.4 mg/L) for B1, from 18.3 to 93 mg/L (mean concentration 47.4 mg/L) for B2, from 21.4 to 215.6 mg/L (mean concentration 119.6 mg/L) for B3, from 20.2 to 107.2 mg/L (mean concentration 81.9 mg/l) for B4, from 8.6 to 36.9 mg/L (mean concentration 26.3 mg/L) for C1, and from 26.7 to 79.3 mg/L (mean concentration 67.1 mg/L) for T2. White and rosé wines (n = 57 and n = 8) were found to have low levels of (+)-catechin (mean concentrations 9.8 and 10.6 mg/L, respectively) and (-)-epicatechin (mean concentrations 5.3 and 6.5 mg/L, respectively). These data provide a basis for the epidemiological evaluation of catechin intake by the consumption of French wine.