Calycosin and Formononetin Induce Endothelium‐Dependent Vasodilation by the Activation of Large‐Conductance Ca2+‐Activated K+ Channels (BKCa)

Tseng, Hisa Hui Ling; Vong, Chi Teng; Leung, George Pak-Heng; Seto, Sai Wang; Kwan, Yiu Wa; Lee, Simon Ming‐Yuen; Hoi, Maggie Pui Man

doi:10.1155/2016/5272531

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…In addition to a direct stimulation, formononetin may potentiate the endothelial NO/cGMP pathway by upregulating eNOS at both the mRNA and protein levels [ 167 ]. In human umbilical vein endothelial cells (HUVECs), formononetin increases NO production and upregulates the expression of eNOS and of neuronal NOS (nNOS) without affecting iNOS [ 168 ]. Formononetin is able to increase eNOS expression via activation of the PI3K/PTEN/Akt and MAPK pathways.…”

Section: Vasorelaxant Effects Of Isoflavones In Vitromentioning

confidence: 99%

The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation

Silva

2021

Biology

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Isoflavones are phytoestrogen compounds with important biological activities, including improvement of cardiovascular health. This activity is most evident in populations with a high isoflavone dietary intake, essentially from soybean-based products. The major isoflavones known to display the most important cardiovascular effects are genistein, daidzein, glycitein, formononetin, and biochanin A, although the closely related metabolite equol is also relevant. Most clinical studies have been focused on the impact of dietary intake or supplementation with mixtures of compounds, with only a few addressing the effect of isolated compounds. This paper reviews the main actions of isolated isoflavones on the vasculature, with particular focus given to their effect on the determinants of blood pressure regulation. Isoflavones exert vasorelaxation due to a multitude of pathways in different vascular beds. They can act in the endothelium to potentiate the release of NO and endothelium-derived hyperpolarization factors. In the vascular smooth muscle, isoflavones modulate calcium and potassium channels, leading to hyperpolarization and relaxation. Some of these effects are influenced by the binding of isoflavones to estrogen receptors and to the inhibition of specific kinase enzymes. The vasorelaxation effects of isoflavones are mostly obtained with plasma concentrations in the micromolar range, which are only attained through supplementation. This paper highlights isolated isoflavones as potentially suitable alternatives to soy-based foodstuffs and supplements and which could enlarge the current therapeutic arsenal. Nonetheless, more studies are needed to better establish their safety profile and elect the most useful applications.

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Section: Vasorelaxant Effects Of Isoflavones In Vitromentioning

confidence: 99%

The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation

Silva

2021

Biology

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“…The ability of FMN to induce endothelial- and NO-dependent vasodilation has been demonstrated in several studies. 24 , 25 , 33 It has also been established that the PI3K/Akt pathway plays a critical role in eNOS expression and NO production. 34 , 35 Thus, we focused on the probable vasodilative effect of FMN and its interaction with the PI3K/Akt signaling pathway in the current study.…”

Section: Discussionmentioning

confidence: 99%

“… 23 Other studies have demonstrated that FMN evokes endothelium-dependent relaxation in rat arterial rings via the upregulation of NO in arterial endothelium through the MAPK pathway, as well as through the stimulation of potassium channels. 24 , 25 However, the precise molecular mechanisms need to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

Formononetin induces vasorelaxation in rat thoracic aorta via regulation of the PI3K/PTEN/Akt signaling pathway

Li¹,

Zhong²,

Tang³

et al. 2018

DDDT

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BackgroundFormononetin (FMN) is an isoflavone that produces arterial vasodilation. However, the underlying molecular mechanisms are unclear.PurposeThe purpose of this study was to explore the vasorelaxant effect and the potential mechanism of FMN in vascular endothelium in isolated rat aorta.MethodsThe thoracic aortas of Sprague Dawley rats were isolated to test the arterial reactivity in the presence of FMN with or without inhibitors. Bioinformatics analyses, including a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and molecular docking methods, were performed to predict therapeutic targets responsible for the vascular protection produced by FMN. We used rat aortic endothelial cells (RAOECs) as an in vitro model to verify the potential mechanism through molecular biological analyses. The production of nitric oxide (NO) metabolites were evaluated via an NO assay kit according to the manufacturer’s instruction. The mRNA expression of eNOS was analyzed by polymerase chain reaction, and the protein levels of PTEN, phosphorylated Akt, and eNOS were measured by Western blot.ResultsWe found that FMN dilated rat aortic rings in a concentration-dependent manner, which was reduced by endothelium denudation and eNOS inhibition. The bioinformatics analyses indicated that FMN activity was associated with the PI3K/PTEN/Akt signaling pathway. Molecular biological studies demonstrated that FMN significantly elevated the levels of NO and eNOS mRNA and markedly increased the protein expression of phosphorylated Akt and eNOS in RAOECs, and decreased PTEN compared with a dimethyl sulfoxide group.ConclusionFMN performs vasorelaxation of the thoracic aorta through activating the PI3K/PTEN/Akt signaling pathway.

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“…), Prunus, Pueraria, and Ononis sp. [5][6][7][8]. Isoflavonoid intake in humans is also increasing due to the use of a variety of dairy products, processed food, and food supplements derived from the aforementioned plants [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The data on the effects of individual purified isoflavonoids themselves are hence largely missing, with some exceptions [12]. Additionally, ex vivo and animal vascular studies have been performed for a limited number of compounds [6,11,13,14], and even less information is available in respect to coronary vessels [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway

et al. 2020

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AbstractThe dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with EC50 below 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl2, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 – 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.

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Calycosin and Formononetin Induce Endothelium‐Dependent Vasodilation by the Activation of Large‐Conductance Ca²⁺‐Activated K⁺ Channels (BK_Ca)

Cited by 6 publications

References 45 publications

The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation

The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation

Formononetin induces vasorelaxation in rat thoracic aorta via regulation of the PI3K/PTEN/Akt signaling pathway

Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway

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