Flavonolignans Inhibit IL1-β-Induced Cross-Talk between Blood Platelets and Leukocytes

Bijak, Michał; Dziedzic, Angela; Synowiec, Ewelina; Śliwiński, Tomasz; Saluk‐Bijak, Joanna

doi:10.3390/nu9091022

Cited by 15 publications

(19 citation statements)

References 39 publications

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“…There are many studies presenting flavonolignans as having strong anti-inflammatory properties [ 52 , 53 , 54 ], resulting in significantly reduced production of pro-inflammatory cytokines. In our previous study, we also documented the anti-inflammatory properties of flavonolignans on IL-1β-induced human blood samples [ 29 ]. For this reason, we decided to verify the toxic effect of flavonolignans on blood platelets’ peripheral blood mononuclear cell.…”

Section: Discussionmentioning

confidence: 99%

“…We observed that silybin and silychristin inhibit the IL-1β-induced formation of blood platelet-leukocyte aggregates in whole blood samples in a dose-dependent manner, as well as leucocyte production of the pro-inflammatory cytokines-IL-2, TNF, INF-α, and INF-γ. Additionally, these two flavonolignans abolished the IL-1β-induced expression of mRNA for IFN-γ and TNF in leucocytes [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Cytotoxicity and Genotoxicity of Flavonolignans in Different Cellular Models

et al. 2017

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Flavonolignans are the main components of silymarin, which represents 1.5–3% of the dry fruit weight of Milk thistle (Silybum marianum L. Gaernt.). In ancient Greece and Romania, physicians and herbalists used the Silybum marianum to treat a range of liver diseases. Besides their hepatoprotective action, silymarin flavonolignans have many other healthy properties, such as anti-platelet and anti-inflammatory actions. The aim of this study was to evaluate the toxic effect of flavonolignans on blood platelets, peripheral blood mononuclear cells (PBMCs) and human lung cancer cell line—A549—using different molecular techniques. We established that three major flavonolignans: silybin, silychristin and silydianin, in concentrations of up to 100 µM, have neither a cytotoxic nor genotoxic effect on blood platelets, PMBCs and A549. We also saw that silybin and silychristin have a protective effect on cellular mitochondria, observed as a reduction of spontaneous mitochondrial DNA (mtDNA) damage in A549, measured as mtDNA copies, and mtDNA lesions in ND1 and ND5 genes. Additionally, we observed that flavonolignans increase the blood platelets’ mitochondrial membrane potential and reduce the generation of reactive oxygen species in blood platelets. Our current findings show for the first time that the three major flavonolignans, silybin, silychristin and silydianin, do not have any cytotoxicity and genotoxicity in various cellular models, and that they actually protect cellular mitochondria. This proves that the antiplatelet and anti-inflammatory effect of these compounds is part of our molecular health mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of the Cytotoxicity and Genotoxicity of Flavonolignans in Different Cellular Models

et al. 2017

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“…Silybin is also studied as a potential anticancer and chemo-preventive agent [ 13 ]. Research performed last year demonstrates that silybin is able to inhibit serine proteases involved in the blood coagulation process [ 14 , 15 ], as well as reduce blood platelets’ response to physiological agonists [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism

2017

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Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, which has been confirmed in various studies. This compound belongs to the flavonoid group known as flavonolignans. Silybin’s structure consists in two main units. The first is based on a taxifolin, the second a phenyllpropanoid unit, which in this case is conyferil alcohol. These two units are linked together into one structure by an oxeran ring. Since the 1970s, silybin has been regarded in official medicine as a substance with hepatoprotective properties. There is a large body of research that demonstrates silybin’s many other healthy properties, but there are still a lack of papers focused on its molecular structure, chemistry, metabolism, and novel form of administration. Therefore, the aim of this paper is a literature review presenting and systematizing our knowledge of the silybin molecule, with particular emphasis on its structure, chemistry, bioavailability, and metabolism.

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“…However, the reduction of platelet response to collagen by flavonolignans was significantly lower than the effect on ADP-induced blood platelet activation. Additionally, we observed that these compounds are able to inhibit cross-talk between blood platelets and the immune response system [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets

et al. 2018

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Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets’ aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets’ ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation.

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Flavonolignans Inhibit IL1-β-Induced Cross-Talk between Blood Platelets and Leukocytes

Cited by 15 publications

References 39 publications

Evaluation of the Cytotoxicity and Genotoxicity of Flavonolignans in Different Cellular Models

Evaluation of the Cytotoxicity and Genotoxicity of Flavonolignans in Different Cellular Models

Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets

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