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Corrective influence food concentrate phenolic compounds of apples in experimental metabolic syndrome in syrian golden hamsters

October 2016
Ukrainian biopharmaceutical journal

DOI:10.24959/ubphj.16.67

License
CC BY 4.0

Authors:

Andriy Zagayko

National University of Pharmacy

Tetiana Briukhanova

Kharkiv National Medical University

У статті відображені результати дослідження доцільності застосування харчового концентрату фенольних сполук яблук, за експериментального метаболічного синдрому у сирійських золотавих хом’ячків. Як препарат порівняння обрано індивідуальну сполуку – епігалокатехін галат. Виявлено, що харчовий концентрат і ЕГКГ виявляють корегуючий вплив щодо патологічних змін вуглеводного та ліпідного обміну, що формуються за модельної патології. При цьому більш виразний корегуючий вплив виявляє харчовий концентрат фенольних сполук яблук, що, очевидно пов’язано з його комплексним антиоксидантним впливом та нормалізацією антиоксидантно-прооксидантного балансу.

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Available via license: CC BY 4.0

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UKRAINIAN BIOPHARMACEUTICAL JOURNAL, No. 5 (46) 2016 ISSN 2311-715X





Національний фармацевтичний університет









Відображені результати дослідження доцільності застосування харчового концентрату фенольних

сполук яблук за експериментального метаболічного синдрому у сирійських золотавих хом’ячків. Як препа-

рат порівняння обрано індивідуальну сполуку – епігалокатехіну галат. Виявлено, що харчовий концентрат

і ЕГКГ чинять коригуючий вплив щодо патологічних змін вуглеводного та ліпідного обміну, що формуються

за модельної патології. При цьому більш виразний коригуючий вплив виявляє харчовий концентрат феноль-

них сполук яблук, що, очевидно, пов’язано з його комплексним антиоксидантним впливом та нормалізацією

антиоксидантно-прооксидантного балансу.

Ключові слова









 



 





































 

 



 

























  







 























  

[38] Біохімія та фармакологія

УКРАЇНСЬКИЙ БІОФАРМАЦЕВТИЧНИЙ ЖУРНАЛ, № 5 (46) 2016ISSN 2311-715X









 









 











 











  



 

















  









глюкози





  імуно-

реактивного інсуліну (ІРІ)

 

in vitro



Показник інсулінорезистентності







триацилгліцеролів (ТАГ)

 



вільних

жирних кислот (ВЖК)

 

ЛПВЩ апо-В-

вмісних ліпопротеїнів



 





































 







 









  





















































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UKRAINIAN BIOPHARMACEUTICAL JOURNAL, No. 5 (46) 2016 ISSN 2311-715X

















 







  



  



















































  















 







  



  









mn

  









    

    

    











mn

  









    

    

    

    



 Біохімія та фармакологія

УКРАЇНСЬКИЙ БІОФАРМАЦЕВТИЧНИЙ ЖУРНАЛ, № 5 (46) 2016ISSN 2311-715X





  







in vivo































  













































































  







 



  











 





   



 





 











 









 









 

 









  





    





UKRAINIAN BIOPHARMACEUTICAL JOURNAL, No. 5 (46) 2016 ISSN 2311-715X

 









 



 





 

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

 

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 

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

 

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 

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 

 

 



[42] Біохімія та фармакологія

УКРАЇНСЬКИЙ БІОФАРМАЦЕВТИЧНИЙ ЖУРНАЛ, № 5 (46) 2016ISSN 2311-715X



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











   









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Beneficial Effects of Quercetin on Obesity and Diabetes

Article

Full-text available

Jan 2011

Scientific research is constantly looking for new molecules that could be used as dietary functional ingredients in the fight against obesity and diabetes, two pathologies highly prevalent in Western societies. In this context, flavonoids represent a group of molecules of increasing interest. The major flavonoid is Quercetin, which belongs to the class called flavonols and is mainly found in apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. It exhibits a wide range of biological functions including anticarcenogenic, anti-inflammatory and antiviral; it also inhibits lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the main effects of Quercetin on obesity and diabetes. The mechanisms of action explaining the effects of Quercetin on these two metabolic disturbances are also considered. Good perspectives have been opened for Quercetin, according to the results obtained either in cell cultures or in animal models. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of this flavonoid on these pathologies. Moreover, the body fat-lowering effect and the improvement of glucose homeostasis need to be confirmed in humans. Animal studies have consistently failed to demonstrate adverse effects caused by Quercetin. In contrast, due to inhibitory effect of Quercetin in cytochrome P450, interactions with drugs can be taken into account when they are administered at the same time than Quercetin.

Quercetin Ameliorates Cardiovascular, Hepatic, and Metabolic Changes in Diet-Induced Metabolic Syndrome in Rats

Article

Full-text available

Apr 2012
J NUTR

Metabolic syndrome is a risk factor for cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). We investigated the responses to the flavonol, quercetin, in male Wistar rats (8-9 wk old) divided into 4 groups. Two groups were given either a corn starch-rich (C) or high-carbohydrate, high-fat (H) diet for 16 wk; the remaining 2 groups were given either a C or H diet for 8 wk followed by supplementation with 0.8 g/kg quercetin in the food for the following 8 wk (CQ and HQ, respectively). The H diet contained ~68% carbohydrates, mainly as fructose and sucrose, and ~24% fat from beef tallow; the C diet contained ~68% carbohydrates as polysaccharides and ~0.7% fat. Compared with the C rats, the H rats had greater body weight and abdominal obesity, dyslipidemia, higher systolic blood pressure, impaired glucose tolerance, cardiovascular remodeling, and NAFLD. The H rats had lower protein expressions of nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and carnitine palmitoyltransferase 1 (CPT1) with greater expression of NF-κB in both the heart and the liver and less expression of caspase-3 in the liver than in C rats. HQ rats had higher expression of Nrf2, HO-1, and CPT1 and lower expression of NF-κB than H rats in both the heart and the liver. HQ rats had less abdominal fat and lower systolic blood pressure along with attenuation of changes in structure and function of the heart and the liver compared with H rats, although body weight and dyslipidemia did not differ between the H and HQ rats. Thus, quercetin treatment attenuated most of the symptoms of metabolic syndrome, including abdominal obesity, cardiovascular remodeling, and NAFLD, with the most likely mechanisms being decreases in oxidative stress and inflammation.

Association of urine acidification with visceral obesity and the metabolic syndrome

Article

Full-text available

Mar 2011
ENDOCR J

Urine acidification is induced by metabolic acidosis which is associated with a high intake of protein-rich diet. The purpose of this study was to investigate the relationship of urine acidification with visceral obesity and the metabolic syndrome. We recruited 1,051 male subjects who underwent health examinations at the Health Care Center in Kinki Central Hospital. Subjects who were treated for hypertension, dyslipidemia, diabetes mellitus, and hyperuricemia and had the past history of chronic liver disease, chronic kidney disease and cancer, were excluded in this study. All subjects were administered to urine pH, blood and physical examinations. Lower urine pH was associated with higher serum urea nitrogen which reflects high intake of protein-rich diet, whereas it had no relation to serum creatinine. Lower urine pH was also associated with an increase in waist circumference, homeostasis model assessment-R, fasting plasma glucose, HbA1c, serum triglyceride, serum uric acid and with a decrease in high density lipoprotein cholesterol. Urine pH was not associated with mean blood pressure. Urine acidification is a characteristic of visceral obesity and the metabolic syndrome. High intake of protein-rich diet may contribute urine acidification, which is associated with various metabolic abnormalities in visceral obesity.

Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: Randomized controlled trial

Article

Full-text available

Sep 2008
BRIT J NUTR

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058 (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se 0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis.

Fructose Induced Leptin Dysfunction and Improvement by Quercetin and Rutin in Rats

Article

Dec 2009

AIM To investigate the dysfunction of leptin underlying insulin resistance syndrome in fructose-fed rats and improvement by lowing uric acid with natural products quercetin and rutin. METHODS Rats were fed with fructose solution for 8 weeks. At week 4, animals received quercetin and rutin, as well as allopurinol. Serum uric acid and insulin levels were measured before and after drug treatment. Leptin levels in serum and hypothalamus, leptin secretion from adipose tissue were used to evaluate the responses of leptin to hyperuricemia and hyperinsulinemia in rats with insulin resistance syndrome. Triglyceride (TG), high dense lipid (HDL) and low dense lipid (LDL) in serum were examined to evaluate dyslipidemia in fructose-fed rats. RESULTS Fructose consumption significantly increased serum uric acid, insulin and leptin levels in rats, and induced a significant increase of leptin secretion by upregulating ob gene expression in adipose tissue. Quercetin and rutin, as well as allopurinol reduced hyperleptinemia and inhibited leptin secretion from adipose tissue. Moreover, fructose-fed rats exhibited leptin level increase in hypothalamus accompanying dyslipidemia. Quercetin, rutin and allopurinol attenuated fructose-induced dyslipidemia in rats, but failed to improve leptin insufficiency in hypothalamus. CONCLUSION These results indicated that fructose consumption might cause hyperleptinemia and leptin insufficiency in the brain, which might be indirectly mediated by hyperinsulinemia and hypertriglyceridemia in rats. Hopouricemic agents quercetin, rutin and allopurinol improved hyperinsulinemia and dyslipidemia, and subsequently regulated leptin dysfunction in fructose-fed rats. This study provided direct evidence that hyperuricemia was associated with hyperleptinemia during fructose consumption, and another pharmacological explanation for lowing uric acid agents to prevent hyperuricemia and leptin dysfunctions in fructose-induced insulin resistance syndrome in rats.

Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: A randomized controlled trial

Article

Jan 2012

Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42; apple, 51 nmol/L, 40, 65; spinach, 86 nmol/L, 68, 110; apple+spinach, 69 nmol/L, 54, 88; P<0.01) and higher nitrite (control, 35 nmol/L, 27, 46; apple, 69 nmol/L, 53, 90; spinach, 99 nmol/L, 76, 129; apple+spinach, 80 nmol/L, 61, 104; P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health.

Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension

Article

Jan 2012

Flavanol-rich diets have been reported to exert beneficial effects in preventing cardiovascular diseases, such as hypertension. We studied the effects of chronic treatment with epicatechin on blood pressure, endothelial function, and oxidative status in deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Rats were treated for 5 weeks with (-)-epicatechin at 2 or 10 mg kg(-1)day(-1). The high dose of epicatechin prevented both the increase in systolic blood pressure and the proteinuria induced by DOCA-salt. Plasma endothelin-1 and malondialdehyde levels and urinary iso-prostaglandin F(2α) excretion were increased in animals of the DOCA-salt group and reduced by the epicatechin 10 mg kg(-1) treatment. Aortic superoxide levels were enhanced in the DOCA-salt group and abolished by both doses of epicatechin. However, only epicatechin at 10 mg kg(-1) reduced the rise in aortic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and p47(phox) and p22(phox) gene overexpression found in DOCA-salt animals. Epicatechin increased the transcription of nuclear factor-E2-related factor-2 (Nrf2) and Nrf2 target genes in aortas from control rats. Epicatechin also improved the impaired endothelium-dependent relaxation response to acetylcholine and increased the phosphorylation of both Akt and eNOS in aortic rings. In conclusion, epicatechin prevents hypertension, proteinuria, and vascular dysfunction. Epicatechin also induced a reduction in ET-1 release, systemic and vascular oxidative stress, and inhibition of NADPH oxidase activity.

Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism

Article

Sep 2010

To study possible insulin sensitizing, anti-inflammatory and anti-oxidative effects of the flavonol quercetin, rats were fed a high-fat diet (19%, w/w) with (HFQ) or without (HF) 0.03% quercetin or a flavonoid-poor low-fat (5%, w/w) maintenance diet (LF) over 4 weeks. Body weight was measured weekly, and plasma concentrations of adiponectin, leptin, insulin, glucose, triacylglycerols, total cholesterol, as well as of markers of inflammation and oxidative stress were measured (12h fasted) at the end of the feeding period. Adiponectin and peroxisome-proliferator-activated-receptor (PPAR)-gamma mRNA were measured in adipose tissue (WAT) by real-time RT-PCR. PPAR-gamma transactivation was investigated by means of a reporter gene assay. HF feeding resulted in elevated fasted plasma glucose concentrations, while HFQ did not differ from LF feeding. In the HFQ group plasma concentrations and WAT mRNA levels of adiponectin were elevated compared with the HF group, however, PPAR-gamma mRNA concentration in WAT was decreased (HFQ vs. HF). Compared to both other groups quercetin feeding significantly reduced oxidative stress, measured by plasma 8-iso-PGF(2alpha), while body weight gain, body composition and plasma leptin levels were not affected. Neither quercetin nor its metabolites induced PPAR-gamma-mediated transactivation in vitro. Adiponectin stimulating effects of quercetin are PPAR-gamma-independent and prevent impairment of insulin sensitivity without affecting body weight and composition.

Effects of epigallocatechin-3-gallate on behavioral impairments induced by psychological stress in rats

Article

May 2010
EXP BIOL MED

This study was conducted to explore the effects of epigallocatechin-3-gallate (EGCG) on cognitive performances in psychological stress rats. An animal model of psychological stress was developed by restraint stress for three weeks. Male Wistar rats were randomly assigned to four groups as follows: normal control group, stress control group and two stress groups with green tea polyphenols (GTPs) and EGCG modulation, respectively. The changes of behavioral performances of rats were examined by the open-field test and step-through test. Results showed that behavioral performances of stress control group were changed abnormally, and they were improved in GTPs and EGCG modulation groups. In addition, plasma levels of cortisol, dopamine, norepinephrine, 5-hydroxytryptamine, interleukin-6 and interleukin-2 were detected. Stress control group had increased contents of cortisol, interleukin-6 and interleukin-2, and meanwhile had declined levels of 5-hydroxytryptamine and catecholamines. These changes in GTPs and EGCG modulation groups were similar to that of the normal control group. The expressions of metallothioneins in the hippocampus were detected by reverse transcription polymerase chain reaction. In contrast with the normal control group, their expressions in all the three stress groups were enhanced clearly. The results suggested that GTPs and EGCG modulation could improve the cognitive impairments induced by psychological stress. The related mechanisms may be involved with the changes of catecholamines, 5-hydroxytryptamine, cytokines and expressions of metallothioneins.

Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats

Article

Jun 2009

The flavonoid quercetin is considered to have beneficial effects on human health. We recently have shown that quercetin-enriched foods reduced the duration of immobility time in a rat forced swimming test, indicating that dietary quercetin is promising as an antidepressant-like factor, whereas its mechanism of action is poorly understood. The aim of this study is to investigate the effects of quercetin on water immersion-restraint (WIR), stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation, which is a major component of stress response and plays an important role in the pathology of depression. Quercetin administration to rats significantly suppressed WIR stress-induced increase of plasma corticosterone and adrenocorticotropic hormone levels as well as the mRNA expression of corticotropin-releasing factor (CRF) in the hypothalamic region. In addition, quercetin modulated the DNA binding activities of glucocorticoid receptor and phosphorylated cyclic adenosine 3',5'-monophosphate (cAMP) response element binding protein as well as the phosphorylation of extracellular signal-regulated kinase 1/2 in the hypothalamic region, all of which are known to regulate the expression of CRF mRNA. Taken together, these results suggest that dietary quercetin attenuates the HPA axis activation by the suppression of the CRF mRNA expression.