Flavonoid‐Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial

Bondonno, Nicola P.; Bondonno, Catherine P.; Blekkenhorst, Lauren C.; Considine, Michael; Maghzal, Ghassan J.; Stocker, Roland; Woodman, Richard; Ward, Natalie C.; Hodgson, Jonathan M.; Croft, Kevin D.

doi:10.1002/mnfr.201700674

Cited by 77 publications

(63 citation statements)

References 47 publications

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“…Citrus species are natural products and notably rich in flavonoid compounds which are famous for multiple therapeutic benefits. Citrus flavonoids have been researching in recent years underlying its beneficial activities such as antioxidation, anti-inflammation, and anti-cardiovascular diseases (Bondonno et al, 2018;Vazhappilly et al, 2019). Additionally, some clinical trials found that plant flavonoids are effective in preventing obesity, type 2 diabetes, and some metabolic syndromes (Guo et al, 2016;Pan et al, 2017), which are strongly associated with NASH.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

Shi

Liu

et al. 2020

Front. Pharmacol.

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Nonalcoholic steatohepatitis (NASH) is a liver disease defined as the dynamic condition of hepatocellular injury during the progress of nonalcoholic fatty liver disease (NAFLD). Total flavonoids from the dry and immature fruits of Citrus Paradisi cv.Changshanhuyou (accepted species name: Citrus × aurantium L) (Qu Zhi Qiao, QZQ) are purified and named TFCH. This study was purposed to investigate and analyze the effect of TFCH on NASH model through Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements pathway in vivo and in vitro. In vivo study was performed using male C57BL/6 mice fed with high fat diet 16 weeks for NASH model. After 7-week modeling, mice in TFCH-treated group were daily treated with intragastric administration of TFCH at 25 mg/kg, 50 mg/kg, 200 mg/kg, respectively, for successive 8 weeks. Histopathological and immunohistochemical analyses were conducted for evaluating severity of NASH-mice model and the effect of TFCH treatment. In vitro experiment was performed by using human LX-2 cells and cultured with Free fatty acid (FFA) (Oleic acid: palmitic: l: 0.5 mmol/L) for 24 h and then treated with TFCH at different concentrations (0, 25, 50, 100, 200 mg/ml) for 6 h,12 h, and 24 h. Anti-apoptosis effect of TFCH on LX-2 cells cultured with FFA was revealed by the CCK-8 assay. Lipid parameters and oxidative stress markers were Frontiers in Pharmacology | www.frontiersin.org measured in vivo and in vitro, results showed that TFCH dose-dependently and greatly increased the antioxidant ability and reduced the oxidative damage in NASH model. The protein expression of Nrf2 and the downstream target genes in mice liver and human LX-2 cells were tested by Western blot analysis to investigate the possible molecular mechanisms of TFCH. Our results indicated that TFCH up-regulated protein expression of these genes and have the significant influence in activating the Nrf2-ARE signaling pathway. This study shows Nrf2-ARE signaling pathway may provide novel therapeutic opportunities for NASH therapy in the future.

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Section: Introductionmentioning

confidence: 99%

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

Shi

Liu

et al. 2020

Front. Pharmacol.

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“…A randomized controlled clinical study was done on flavonoid-rich Cripps Pink apple skins with individuals who are at risk for CVD to improve endothelial function [13]. Due to this randomized controlled clinical study, the term flavonoids are used instead of polyphenols and will be used only for this section of the review.…”

Section: Endothelial and Arterial Functionmentioning

confidence: 99%

Benefits and Preparation Effects on Polyphenol-Rich Fruits and Vegetables Towards Cardiovascular Disease Prevention

Hawana¹,

Alraei²

2019

J Nutr Food Sci

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Individuals with cardiovascular disease are advised to consume fruits and vegetables due to their potential health benefits of their polyphenol-rich components. The main precursors that lead to cardiovascular disease are endothelial dysfunction and arterial stiffness. These metabolic dysfunctions can be improved by bioavailability of polyphenol-rich foods such as hesperidin from citrus fruits or anthocyanidins that give the color of fruits and vegetables. Polyphenolrich foods can increase beneficial biological processes including the expression of nitric oxide in the blood vessel to enhance vascular tone by vasodilation. However, polyphenols can be lost during absorption and post-absorption by interactions with other macromolecules. Additionally, the cooking methods and preparation of certain polyphenol-rich fruits and vegetables can cause extreme loss of polyphenols. Recent studies have demonstrated various cooking methods that can enhance the nutrient quality of polyphenols and their bioavailability. Understanding the absorption, biological processes and cooking methods of polyphenol-rich fruits and vegetables can help link the benefits of prevention or treatment in cardiovascular disease risk factors.

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“…In another study by Croft et al (2017), the Hmox1 induction effects of 9 purified flavonoids (5 unmetabolized flavonoids and 4 metabolites) in HAECs were comparatively scrutinized. Quercetin, rather than its methyl or sulfate metabolites, presented excellent induction effects on Hmox1 at physiologically relevant concentrations (from 5 to 10 lM).…”

Section: Induction Of Antioxidant Enzymesmentioning

confidence: 99%

“…Endothelial dysfunction occurs early in the pathological process of atherosclerosis, and is an independent predictor of cardiovascular disease. Over last two decades, numerous intervention studies with certain flavonoids (Bondonno et al, ; Loke et al, ; Schroeter et al, ) or foods rich in flavonoids (Agewall et al, ; Bondonno et al, ; Nakayama, Tsuge, Sawada, & Higashi, ) have shown improvements in cardiovascular risk factors such as endothelial function. Additionally, the potential protective effects of different flavonoids on vascular endothelial function are probably dependent on their structural properties (Hooper et al, ).…”

Section: Introductionmentioning

confidence: 99%

A review on the structure-activity relationship of dietary flavonoids for protecting vascular endothelial function: Current understanding and future issues

Zhang

Wei

et al. 2018

J Food Biochem

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Nowadays dietary flavonoids attract considerable attention in the prevention of cardiovascular diseases, even though the definitive structure–activity relationships (SARs) of flavonoids are not completely understood. This review exclusively aims to summarize recent evidence for the correlation between structural features of dietary flavonoids and effects on vascular endothelial function (EF). In human studies, the diets rich in one of six flavonoid subclasses namely, flavonol, flavone, flavanol, flavanone, anthocyanin, and isoflavone were reported to have positive effects on EF. However, the clinical evidence supporting SAR establishment was limited and often inconclusive. In in vitro models, the evidence for the activities of metabolized and unmetabolized flavonoids in three protective pathways of EF: nitric oxide bioavailability, induction of antioxidant enzymes, and anti‐inflammation are highlighted. The specific structural characteristics favorable in modulation of each pathway are summarized. Nevertheless, the roles of the substituent property of flavonoid metabolites on endothelial cells function remain to be investigated. Practical applications Due to the potential benefits for cardiovascular health, dietary flavonoids have come into the focus of utilization as a nutraceutical ingredient in food and pharmaceutical industries. Since there are many hundreds of flavonoids in human diets, thus it is very necessary to known if specific structural motifs could confer some flavonoids with higher cardiovascular bioactivity than others. The discussion on SARs for protecting vascular endothelial function will give us important information on utilization of flavonoids in human precise nutrition.

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Flavonoid‐Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial

Abstract: A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically.

Cited by 77 publications

References 47 publications

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

Benefits and Preparation Effects on Polyphenol-Rich Fruits and Vegetables Towards Cardiovascular Disease Prevention

A review on the structure-activity relationship of dietary flavonoids for protecting vascular endothelial function: Current understanding and future issues

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