Effects of 2,3-Dehydrosilybin and Its Galloyl Ester and Methyl Ether Derivatives on Human Umbilical Vein Endothelial Cells

Karaś, Daniel; Gažák, Radek; Valentová, Kateřina; Chambers, Christopher S.; Pivodová, Veronika; Biedermann, David; Křenková, Alena; Oborná, I; Kuzma, Marek; Cvačka, Josef; Ulrichová, Jitka; Křen, Vladimı́r

doi:10.1021/acs.jnatprod.5b00905

Cited by 14 publications

(12 citation statements)

References 35 publications

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“…Moreover, 2,3-dehydrosilydianin (but not silybin, silychristin, silydianin, 2,3-dehydrosilybin, or 2,3-dehydrosilychristin) was found to activate Nrf2 and upregulate NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells [11]. 2,3-Dehydrosilybin and its gallates were also more efficient inhibitors of angiogenesis that silybin and silybin derived gallates [12,13]. In a more complex model, 2,3-dehydrosilybin (and especially the A enantiomer) displayed lifespan-extension effect superior to that of silybin, isosilybin, silychristin and silydianin in Caenorhabditis elegans [14].…”

Section: Resultsmentioning

confidence: 99%

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Valentová

Biedermann

Křen

2019

CA16112 - Luxemburg 2019

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Silybum marianum fruit extract silymarin displays various biological activities, which are attributed mostly to its major component silybin. However, silymarin contain several other isomeric flavonolignans (isosilybin, silychristin, silydianin) and their oxidation products, the 2,3-dehydroflavonolignans (2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin). The latter compounds were found to be 1-2 orders of magnitude more efficient radical scavengers, reducing, chelating, cytoprotective, anti-aging, anti-cancer and anti-angiogenic agents than the parent flavonolignans. Although 2,3-dehydroflavonolignans occur in silymarin as minorities, they seem to be responsible for the majority of the biological activity and therefore have potential for the prevention of chronic diseases.

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Section: Resultsmentioning

confidence: 99%

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Valentová

Biedermann

Křen

2019

CA16112 - Luxemburg 2019

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“…In contrast to published data [8], no higher activity of dehydrosilybin compounds was observed. This fact may be associated with higher cytotoxicity of dehydroflavonolignans [29] or with the different methodological approach to antioxidant capacity determination [8].…”

Section: Discussionmentioning

confidence: 99%

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

et al. 2020

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Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

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“…However, we use here the term silybin as it is also preferred by reference literature, for example, Merck Index and Chemical Abstracts. In addition to silybin, other silymarin flavonolignans were found to possess distinct biological properties, often more pronounced than silybin 14–24 . Importantly, their sulfate metabolites also possess some distinct effects, for example, vasorelaxant properties 25,26 …”

Section: Introduction: Silymarin Its Constituents and Pharmacodynamic Potentialmentioning

confidence: 99%

Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin

Tvrdý

Pourová

Jirkovský

et al. 2021

Medicinal Research Reviews

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Silymarin is an extract from the seeds (fruits) of Silybum marianum that contains flavonolignans and flavonoids. Although it is frequently used as a hepatoprotective agent, its application remains somewhat debatable, in particular, due to the low oral bioavailability of flavonolignans. Moreover, there are claims of its potential interactions with concomitantly used drugs. This review aims at a systematic summary and critical assessment of known information on the pharmacokinetics of particular silymarin flavonolignans. There are two known major reasons for poor systemic oral bioavailability of flavonolignans: (1) rapid conjugation in intestinal cells or the liver and (2) efflux of parent flavonolignans or formed conjugates back to the lumen of the gastrointestinal tract by intestinal cells and rapid excretion by the liver into the bile. The metabolism of phase I appears to play a minor role, in contrast to extensive conjugation and indeed the unconjugated flavonolignans reach low plasma levels after common doses. Only about 1%–5% of the administered dose is eliminated by the kidneys. Many in vitro studies tested the inhibitory potential of silymarin and its components toward different enzymes and transporters involved in the absorption, metabolism, and excretion of xenobiotics. In most cases, effective concentrations are too high to be relevant under real biological conditions. Most human studies showed no silymarin–drug interactions explainable by these suggested interferences. More interactions were found in animal studies, likely due to the much higher doses administered.

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Effects of 2,3-Dehydrosilybin and Its Galloyl Ester and Methyl Ether Derivatives on Human Umbilical Vein Endothelial Cells

Cited by 14 publications

References 35 publications

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin

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