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

Abstract

<jats:title>Abstract</jats:title><jats:p>The 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.</jats:p>

The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action

“…Flavonoids, such as anthocyanins [ 65 , 66 ], flavones (i.e., luteolin) [ 67 ], flavanones (i.e., naringin) [ 68 ], flavan-3-ols (i.e., epicatechin) [ 69 ], flavonols (i.e., kaempferol) [ 70 ] and isoflavones [ 71 ], and resveratrol [ 72 , 73 ] may play a direct role in improving the bioavailability in the bloodstream of NO by increasing the activation of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) provided by modulation of signal transduction, for instance through the phosphatidylinositol 3-kinase (PI3K)/Akt or the adenosine monophosphate-activated protein kinase (AMPK) pathways [ 67 ]. Together with other polyphenols, such as caffeic acid [ 74 ], kaempferol [ 75 ], quercetin [ 76 ], luteolin [ 77 ], and biochanin A [ 78 ], these compounds may exert vasorelaxing effects also by acting on vascular smooth muscle cells directly (through activation of BK channels or inhibition of Ca 2+ channels) or indirectly (through activation of Ca 2+ -activated K + channels in endothelial cells, leading to hyperpolarization and inhibition of Ca 2+ influx to vascular smooth muscle cells), eventually limiting construction and leading to vasorelaxation [ 79 ]. However, some polyphenols, such as resveratrol, have been shown to act through more than one of the aforementioned mechanisms [ 80 ].…”

Vasorelaxation endothelium-independent of the ethyl acetate phase from aerial parts of Solanum paludosum Moric. envolves channels-calcium L-type blockade

“…The chemical analyses from SP-AcOEt showed flavonoids and alkamide (Silva et al, 2002), maybe those flavonoids had induced blockade the CaV-channels. Because flavonoids and phenol compounds have been presented inhibiting contractions on smooth and cardiac muscles by CaV-channels blockade (Vourela et al, 1997;Penso et al, 2014;Fusi et al, 2017) and flavones inhibited contractions induced by Ca 2+ (Lin et al, 1997;De Rojas et al, 1999;Tew et al, 2020;Migkos et al, 2020). The calcium-blockers decrease Ca 2+ -level on vascular smooth muscle, resulting vascular tonus relaxation and decreasing blood pressure (Kochegarov, 2003), and are include medicines, frequently, prescribe for treatment of hypertension (Brașoveanu et al, 2019).…”

Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators

“…While the access to the site of action of the latter two flavonoids might be prevented by the presence of the glycoside moiety, further experiments are needed to clarify the contradictory behaviour of butin. Tectoridin inactivity is complementary to the data obtained in the same preparation precontracted by phenylephrine [ 63 ].…”