Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice

Jung, Un Ju; Lee, Mi-Kyung; Park, Yong Bok; Kang, Mi Ae; Choi, Myung‐Sook

doi:10.1016/j.biocel.2005.12.002

Cited by 372 publications

(285 citation statements)

References 69 publications

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“…Jung et al 27 showed that similar results were accompanied by the inhibition of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and CHOL acyltransferases (ACAT) activities, and an increase in the faecal CHOL. Inhibitors of hepatic HMG-CoA reductase, a key enzyme in CHOL synthesis, are wellestablished drugs for the treatment of hypercholesterolemia and decrease the incidence of dyslipidaemia in diabetic subjects 31 .…”

Section: Discussionmentioning

confidence: 92%

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

Menichini

Tundis

Loizzo

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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This study aimed to investigate the antidiabetic, antilipidaemic and antioxidant activities of Citrus medica cv Diamante (Rutaceae) hydroalcoholic (CD) peel extract in Zucker diabetic fatty (ZDF) rats. The ability of CD to protect against oxidative stress was investigated by using different in vitro assays and in vivo by using the reactive oxygen metabolites-derived compounds (d-ROMs) test and the biological antioxidant potential test (BAP). Two different doses of CD extract (300 and 600 mg/kg/die) were administered at ZDF rats for 4 weeks. CD reduced cholesterol and triglycerides levels. A dose-dependent effect on body weight and serum glucose levels was observed. A decrease of d-ROMs and an increase of BAP were recorded by using the dose of 600 mg/kg. The extract inhibited lipid peroxidation (IC 50 value of 0.23 mg/ml). These findings suggest as an efficient phytotherapeutic approach in combating hyperlipidaemic and hyperglycaemic disorders.

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Section: Discussionmentioning

confidence: 92%

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

Menichini

Tundis

Loizzo

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…mice, naringin lowered hyperlipidemia and hyperglycemia through regulating the lipid metabolism and affecting the gene expression of glucose-regulating enzymes (32). In mice fed high fat diet, naringin could activate AMPK-mediated MAPKs signaling pathway, resulting in the reduction of insulin resistance, hyperglycemia, and hyperlipidemia (22).…”

Section: Discussionmentioning

confidence: 99%

Naringin ameliorates endothelial dysfunction in fructose-fed rats

et al. 2018

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Abstract. High fructose consumption is associated with metabolic disorders including hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin, a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering, antioxidant, and cardiovascular protective properties. Therefore, the present study investigated the effect of naringin on fructose-induced endothelial dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were given 10% fructose in drinking water for 12 weeks, whereas control rats were fed drinking water alone. Naringin (100 mg/kg) was orally administered to fructose fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples were collected for measurement of blood glucose, serum lipid profile and total nitrate/nitrite (NOx). Vascular function was assessed by isometric tension recording. Aortic expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot analysis. Fructose feeding induced increased levels of blood glucose, total cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose reduced acethycholine-induced vasorelaxation, without affecting sodium nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with naringin restored fructose-induced metabolic alterations and endothelial dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in aortae. These alterations were improved by naringin treatment. The results of the present study suggested that naringin treatment preserves endothelium-dependent relaxation in aortae from fructose fed rats. This effect is primarily mediated through an enhanced NO bioavailability via increased eNOS activity and decreased NO inactivated to peroxynitrite in aortae.

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“…It is the rate-limiting step in the pathway. Decreased expression of ACAT2 may suppress the biosynthesis of cholesterol, ameliorating hyperlipidemia in type 2 diabetic livers (28,29). NSDHL encodes a 3-β-hydroxysterol dehydrogenase, which is thought to function in the demethylation of sterol precursors in one of the later steps of cholesterol biosynthesis (30).…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics study on the protective mechanism of phlorizin on hepatic damage in diabetic db/db mice

Gao

2012

Mol Med Report

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Abstract. Although phlorizin has been used in the treatment of diabetes mellitus for over 100 years, the underlying molecular mechanisms have not been fully elucidated. This study investigated the effect of phlorizin on body weight, blood glucose, blood triglycerides (TG), blood total cholesterol (TC), as well as overall changes in protein expression in db/db diabetic mouse liver. Phlorizin significantly decreased body weight gain and the levels of glucose, TC and TG in blood. Isobaric tag for relative and absolute quantitation (iTRAQ) quantitative proteomics profiling revealed that phlorizin interfered with the processes of carbohydrate metabolism, fatty acid biosynthesis and β-oxidation, cholesterol biosynthesis, and free radical scavenging by affecting the expression of key proteins in these processes. Ingenuity Pathway Analysis successfully established several pathway networks, in which many differentially expressed proteins were involved. The differential expression of several proteins was validated by western blotting. Our study offers important information on the mechanism of phlorizin treatment in diabetes mellitus, particularly in the liver. IntroductionType 2 diabetes is one of the most common endocrine diseases in developed countries, which is caused by absolute or relative deficiencies in insulin secretion or insulin action (1). Chronic hyperglycemia is the major biochemical alteration in type 2 diabetes. Moreover, individuals with type 2 diabetes usually display a marked disruption of lipid metabolism, with an abnormal accumulation of fat in various tissues including the liver (2). Hyperglycemia and hyperlipidemia not only impair β-cell function and increase insulin resistance in peripheral tissues, such as the muscle, liver, and adipose tissue (3,4), but also induce oxidative stress reactions, which cause initiation and progression of diabetes-related diseases (5,6). Consequently, regulation of dyslipidemia and reduction in oxidative stress have been regarded as important treatment methods for alleviating diabetes and its complications.Phlorizin (glucose,1-[2-(β.D-glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-1-propanone) is a member of the chalcone class of organic compounds and is mainly distributed in the plants of the genus Malus (7). Phlorizin has multiple pharmacological activities, such as anti-oxidative, estrogenic and anti-estrogenic activities, memory improvement and cardioprotective activities (8-11). Reports show that phlorizin inhibits intestinal glucose uptake and renal glucose reabsorption by inhibiting the sodium D-glucose cotransporter (10,12). Phlorizin has been reported to normalize the effects of insulin on glucose metabolism in the liver and other peripheral tissues (13). However, little is known regarding the effect of phlorizin on hepatic damage associated with type 2 diabetes.The rapidly emerging field of quantitative proteomics provides a powerful technique -isobaric tag for relative and absolute quantitation (iTRAQ) labeling combined with liquid chromatograph...

show abstract

Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice

Cited by 372 publications

References 69 publications

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

Naringin ameliorates endothelial dysfunction in fructose-fed rats

Quantitative proteomics study on the protective mechanism of phlorizin on hepatic damage in diabetic db/db mice

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