Most cited article - PubMed ID 31554252
The Effect of Silymarin Flavonolignans and Their Sulfated Conjugates on Platelet Aggregation and Blood Vessels Ex Vivo
Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both - the central and peripheral veins. Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet effects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.
- Keywords
- Anticoagulation, Antiplatelet effects, COVID-19, Circulation, Comorbidities, Health policy, Individualized patient profile, Ischemic stroke, Molecular pathways, Natural drugs, Phytochemicals, Predictive preventive personalized medicine, Primary, secondary, tertiary care, Targets, Therapeutic modalities, Thrombosis, Treated cancers, Vascular disease,
- Publication type
- Journal Article MeSH
- Review MeSH
This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.
- Keywords
- Silybum marianum, chirality, dehydroflavonolignan, diastereomer, flavonoid, flavonolignan, isosilybin, milk thistle, silibinin, silybin, silychristin, silydianin, silymarin,
- MeSH
- Anti-Infective Agents chemistry pharmacology MeSH
- Antioxidants chemistry pharmacology MeSH
- Antineoplastic Agents, Phytogenic chemistry pharmacology MeSH
- Humans MeSH
- Silybin chemistry pharmacology MeSH
- Stereoisomerism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Anti-Infective Agents MeSH
- Antioxidants MeSH
- Antineoplastic Agents, Phytogenic MeSH
- Silybin MeSH