Bisphenols, endocrine disrupting chemicals, have frequently been used for producing food packaging materials. The best-known member, bisphenol A (BPA), has been linked to impaired foetal development in animals. Possible negative effects of BPA on human health have resulted in the production of novel, so-called next-generation (NextGen) bisphenols whose effects on humans are much less explored or even missing. This review aimed to summarise and critically assess the main findings and shortages in current bisphenol research in relation to their potential impact on the cardiovascular system in real biological exposure. Because of the common presence of bisphenols in daily use products, humans are clearly exposed to these compounds. Most data are available on BPA, where total serum levels (i.e. included conjugated metabolite) can reach up to ∼430 nM, while free bisphenol levels have been reported up to ∼80 nM. Limited data are available for other bisphenols, but maximal serum levels of bisphenol S have been reported (680 nM). Such levels seem to be negligible, although in vitro studies have showed effects on ion channels, and thyroid, oestrogenic and androgenic receptors in low micromolar concentrations. Ex vivo studies suggest vasodilatory effects of bisphenols. This stays in clear contrast to the elevation of arterial blood pressure documented in vivo and in observatory cross-sectional human studies. Bisphenols are also claimed to have a negative effect on lipidic spectrum and coronary artery disease. Regardless, the reported data are generally inconsistent and unsatisfactory. Hence novel well-designed studies, testing in particular NextGen bisphenols, are needed.

Silymarin is a traditional drug and food supplement employed for numerous liver disorders. The available studies indicate that its activities may be broader, in particular due to claimed benefits in some cardiovascular diseases, but the contributions of individual silymarin components are unclear. Therefore, we tested silymarin flavonolignans as pure diastereomers as well as their sulfated metabolites for potential vasorelaxant and antiplatelet effects in isolated rat aorta and in human blood, respectively. Eleven compounds from a panel of 17 tested exhibited a vasorelaxant effect, with half maximal effective concentrations (EC₅₀) ranging from 20 to 100 µM, and some substances retained certain activity even in the range of hundreds of nM. Stereomers A were generally more potent as vasorelaxants than stereomers B. Interestingly, the most active compound was a metabolite—silychristin-19-O-sulfate. Although initial experiments showed that silybin, 2,3-dehydrosilybin, and 2,3-dehydrosilychristin were able to substantially block platelet aggregation, their effects were rapidly abolished with decreasing concentration, and were negligible at concentrations ≤100 µM. In conclusion, metabolites of silymarin flavonolignans seem to have biologically relevant vasodilatory properties, but the effect of silymarin components on platelets is low or negligible.

Interaction of flavonoids with transition metals can be partially responsible for their impact on humans. Stoichiometry of the iron/copper complex with a flavonoid glycoside isoquercitrin, a frequent component of food supplements, was assessed using competitive and non-competitive methods in four (patho)physiologically-relevant pH values (4.5. 5.5, 6.8, and 7.5). Isoquercitrin chelated all tested ions (Fe²⁺, Fe³⁺, Cu²⁺, and Cu⁺) but its affinity for Cu⁺ ions proved to be very low. In general, the chelation potency dropped with pH lowering. Metal complexes of 1:1 stoichiometry were mostly formed, however, they were not stable and the stoichiometry changed depending on conditions. Isoquercitrin was able to reduce both Cu²⁺ and Fe³⁺ ions at low ratios, but its reducing potential was diminished at higher ratios (isoquercitrin to metal) due to the metal chelation. In conclusion, this study emphasizes the need of using multiple different methods for the assessment of chelation potential in moderately-active metal chelators, like flavonoids.