Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism

Lau, Yeh Siang; Tian, Xiaoyu; Huang, Yü; Murugan, Dharmani Devi; Achike, Francis I.; Mustafa, Mohd Rais

doi:10.1016/j.bcp.2012.11.010

Cited by 61 publications

(53 citation statements)

References 30 publications

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“…There is evidence that phosphorylation of eNOS at serine 1117 is a crucial target for intervention to improve endothelial dysfunction (15). In addition, there is growing evidence that an overproduction of ROS, which is generally generated by a cellular disturbance in glucose or/and lipid metabolism leads to the degradation of NO (39)(40)(41). Superoxide rapidly reacts with NO to form the powerful oxidant peroxynitrite which causes the nitration of proteins leading to the impairing of the function of cellular proteins including eNOS protein (15).…”

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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Section: Discussionmentioning

confidence: 99%

Naringin ameliorates endothelial dysfunction in fructose-fed rats

et al. 2018

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“…The amount of superoxide anion formation was determined using the lucigenin-enhanced chemiluminescence method (Lau et al, 2013). Briefly, isolated mouse aortic rings were pre-incubated for 45 min at 37°C in 2 mL of Krebs-HEPES buffer (in mmol L −1 : NaCl 99.0, NaHCO3 25, KCl 4.7, KH2PO4 1.0, MgSO4 1.2, glucose 11.0, CaCl2 2.5 and Na-HEPES 20.0) in the presence of diethylthiocarbamic acid (1 mmol L −1 ) to inactivate superoxide dismutase (SOD) and β-nicotinamide adenine dinucleotide phosphate (0.1 mmol L −1 ), as substrate for NADPH oxidase.…”

Section: Detection Of Vascular Superoxide Formationmentioning

confidence: 99%

Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II‐mediated BMP4‐oxidative stress cascade

Lau

Tian

Mustafa

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEBoldine is a potent natural antioxidant present in the leaves and bark of the Chilean boldo tree. Here we assessed the protective effects of boldine on endothelium in a range of models of diabetes, ex vivo and in vitro. EXPERIMENTAL APPROACHVascular reactivity was studied in mouse aortas from db/db diabetic and normal mice. Reactive oxygen species (ROS) production, angiotensin AT1 receptor localization and protein expression of oxidative stress markers in the vascular wall were evaluated by dihydroethidium fluorescence, lucigenin enhanced-chemiluminescence, immunohistochemistry and Western blot respectively. Primary cultures of mouse aortic endothelial cells, exposed to high concentrations of glucose (30 mmol L −1 ) were also used. KEY RESULTSOral treatment (20 mg kg , 12 h) enhanced endotheliumdependent aortic relaxations of db/db mice. Boldine reversed impaired relaxations induced by high glucose or angiotensin II (Ang II) in non-diabetic mouse aortas while it reduced the overproduction of ROS and increased phosphorylation of eNOS in db/db mouse aortas. Elevated expression of oxidative stress markers (bone morphogenic protein 4 (BMP4), nitrotyrosine and AT1 receptors) were reduced in boldine-treated db/db mouse aortas. Ang II-stimulated BMP4 expression was inhibited by boldine, tempol, noggin or losartan. Boldine inhibited high glucose-stimulated ROS production and restored the decreased phosphorylation of eNOS in mouse aortic endothelial cells in culture. CONCLUSIONS AND IMPLICATIONSBoldine reduced oxidative stress and improved endothelium-dependent relaxation in aortas of diabetic mice largely through inhibiting ROS overproduction associated with Ang II-mediated BMP4-dependent mechanisms. AbbreviationsAng II, angiotensin II; BMP4, bone morphogenic protein 4; MAEC, mouse aortic endothelial cells BJP British Journal of Pharmacology

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“…Hyperglycaemia-related oxidative stress impairs vascular function in association with activation of the PKC, polyol pathway and formation of advanced glycation end products (Lau et al, 2013;Renaud et al, 2014). Hyperglycaemia causes excessive ROS formation, particularly superoxide anions (Jay et al, 2006), and ROS overproduction is involved in the development of beta cell dysfunction (Malin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Uncoupling protein‐2 mediates the protective action of berberine against oxidative stress in rat insulinoma INS‐1E cells and in diabetic mouse islets

Liu

Gao

et al. 2014

British J Pharmacology

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Background and PurposeUncoupling protein‐2 (UCP2) may regulate glucose‐stimulated insulin secretion. The current study investigated the effects of berberine, an alkaloid found in many medicinal plants, on oxidative stress and insulin secretion through restoration of UCP2 expression in high glucose (HG)‐treated INS‐1E cells and rat islets or in db/db mouse islets.Experimental ApproachMouse and rat pancreatic islets were isolated. Nitrotyrosine, superoxide dismutase (SOD)‐1 and UCP2 expression and AMPK phosphorylation were examined by Western blotting. Insulin secretion was measured by elisa. Mitochondrial reactive oxygen species (ROS) production was detected by confocal microscopy.Key ResultsIncubation of INS‐1E cells and rat islets with HG (30 mmol·L−1; 8 h) elevated nitrotyrosine level, reduced SOD‐1 and UCP2 expression and AMPK phosphorylation, and inhibited glucose‐stimulated insulin secretion. HG also increased mitochondrial ROS in INS‐1E cells. Co‐treatment with berberine inhibited such effects. The AMPK inhibitor compound C, the UCP2 inhibitor genipin and adenovirus ucp2 shRNA inhibited these protective effects of berberine. Furthermore, compound C normalized berberine‐stimulated UCP2 expression but genipin did not affect AMPK phosphorylation. Islets from db/db mice exhibited elevated nitrotyrosine levels, reduced expression of SOD‐1 and UCP2 and AMPK phosphorylation, and decreased insulin secretion compared with those from db/m+ mice. Berberine also improved these defects in diabetic islets and genipin blocked the effects of berberine.Conclusions and ImplicationsBerberine inhibited oxidative stress and restored insulin secretion in HG‐treated INS‐IE cells and diabetic mouse islets by activating AMPK and UCP2. UCP2 is an important signalling molecule in mediating anti‐diabetic effects of berberine.

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Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism

Cited by 61 publications

References 30 publications

Naringin ameliorates endothelial dysfunction in fructose-fed rats

Naringin ameliorates endothelial dysfunction in fructose-fed rats

Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II‐mediated BMP4‐oxidative stress cascade

Uncoupling protein‐2 mediates the protective action of berberine against oxidative stress in rat insulinoma INS‐1E cells and in diabetic mouse islets

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