Covering: 2015 up to 2022 (Feb)Silymarin, an extract of milk thistle (Silybum marianum) fruits, has been used in various medicinal applications since ancient times. A major component of silymarin is the flavonolignan silybin and its relatives isosilybin, silychristin, silydianin, 2,3-dehydrosilybin, and some others. Except for silydianin, they occur in nature as two stereomers. This review focuses on recent developments in chemistry, biosynthesis, modern advanced analytical methods, and transformations of flavonolignans specifically reflecting their chirality. Recently described chemotypes of S. marianum, but also the newest findings regarding the pharmacokinetics, hepatoprotective, antiviral, neuroprotective, and cardioprotective activity, modulation of endocrine functions, modulation of multidrug resistance, and safety of flavonolignans are discussed. A growing number of studies show that the respective diastereomers of flavonolignans have significantly different activities in anisotropic biological systems. Moreover, it is now clear that flavonolignans do not act as antioxidants in vivo, but as specific ligands of biological targets and therefore their chirality is crucial. Many controversies often arise, mainly due to the non-standard composition of this phytopreparation, the use of various undefined mixtures, the misattribution of silymarin vs. silybin, and also the failure to consider the chemistry of the respective components of silymarin.

• MeSH
• antioxidancia farmakologie   MeSH
• ostropestřec mariánský chemie   MeSH
• silibinin MeSH
• silymarin * chemie   farmakologie   MeSH
• tradiční lékařství MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Prezentovaná studie měla za cíl porovnat obsah silybinu ve vybraných potravních doplňcích obsahujících silymarin dostupných v České republice. Stanovení silybinu bylo provedeno pomocí HPLC/UV. Naše výsledky ukazují, že většina potravních doplňků obsahuje silybin v referenčním rozmezí 20–40 %. Výrobky NaturProdukt® Silymarin forte s obsahem 40 % silybinu (80,00 ± 0,50 mg) a Nefdesanté® Silymarin ostropestřec s obsahem 33 % silybinu (81,58 ± 0,14 mg) patří mezi výrobky s vysokým obsahem této přírodní látky. Na druhou stranu nejméně silybinu bylo naměřeno u přípravku WALMARK® Ostropestřec mariánský (< 20 %). Výsledky naznačují, že většina z testovaných potravních doplňků je kvalitní a obsahuje deklarované množství obsahových látek.

The aim of this study was to determine the amount of silybin in selected nutraceuticals containing silymarin available in the Czech Republic. The determination of silybin was performed using HPLC/UV. Results show that almost all of the tested nutraceuticals contain the sufficient amount of silybin (range 20–40 %). NaturProdukt® Silymarin forte contained 40 % of silybin (80.00 ± 0.50 mg) and Nefdesanté® Silymarin ostropestřec contained 33 % of silybin (81.58 ± 0.14 mg). Both can be included among the products with high silybin content. On the other hand, the lowest amount of silybin was measured in WALMARK® Ostropestřec mariánský (< 20 %). Our results suggest that almost all of the tested products are of high quality and contain the declared amount of constituents.

• MeSH
• hodnocení léčiv MeSH
• lidé MeSH
• ostropestřec mariánský * MeSH
• potravní doplňky MeSH
• silibinin MeSH
• silymarin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie 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.

• MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• fytogenní protinádorové látky chemie   farmakologie   MeSH
• lidé MeSH
• silibinin chemie   farmakologie   MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Flavonolignans from the seeds of the milk thistle (Silybum marianum) have been extensively used in folk medicine for centuries. Confirmation of their properties as hepatoprotective, antioxidant and anticancer has been obtained using standardized extracts and purified flavonolignans. Information on their potential effect on Leishmania is very scarce. We have investigated the effect of silymarin, silybin and related flavonolignans on the multiplication of promastigotes in vitro and ex vivo on intracellular amastigotes of L. infantum (Li) and L. donovani (Ld), causative agents of human and canine visceral leishmaniasis (VL). In addition, the potential synergistic effect of the most active molecule and well-established antileishmanial drugs against promastigotes was explored. Dehydroisosilybin A elicited the highest inhibition against Ld and Li promastigotes with an approximate IC50 of 90.23 µM. This molecule showed a moderate synergism with amphotericin B (AmB) but not with SbIII or paromomycin, although it was ineffective against amastigotes. Antileishmanial activity on intracellular amastigotes of the two diastereoisomers of dehydrosilybin (10 µM) was comparable to that elicited by 0.1 µM AmB. Antiproliferative activity and safety of flavonolignans suggest the interest of exploring their potential value in combination therapy against VL.

• MeSH
• amfotericin B farmakologie   MeSH
• antiprotozoální látky farmakologie   MeSH
• Leishmania donovani účinky léků   MeSH
• Leishmania infantum účinky léků   MeSH
• leishmanióza viscerální metabolismus   MeSH
• lidé MeSH
• psi MeSH
• silibinin MeSH
• silymarin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Mesocestoides vogae larvae represent a suitable model for evaluating the larvicidal potential of various compounds. In this study we investigated the in vitro effects of three natural flavonolignans-silybin (SB), 2,3-dehydrosilybin (DHSB) and silychristin (SCH)-on M. vogae larvae at concentrations of 5 and 50 μM under aerobic and hypoxic conditions for 72 h. With both kinds of treatment, the viability and motility of larvae remained unchanged, metabolic activity, neutral red uptake and concentrations of neutral lipids were reduced, in contrast with a significantly elevated glucose content. Incubation conditions modified the effects of individual FLs depending on their concentration. Under both sets of conditions, SB and SCH suppressed metabolic activity, the concentration of glucose, lipids and partially motility more at 50 μM, but neutral red uptake was elevated. DHSB exerted larvicidal activity and affected motility and neutral lipid concentrations differently depending on the cultivation conditions, whereas it decreased glucose concentration. DHSB at the 50 μM concentration caused irreversible morphological alterations along with damage to the microvillus surface of larvae, which was accompanied by unregulated neutral red uptake. In conclusion, SB and SCH suppressed mitochondrial functions and energy stores, inducing a physiological misbalance, whereas DHSB exhibited a direct larvicidal effect due to damage to the tegument and complete disruption of larval physiology and metabolism.

• MeSH
• antioxidancia farmakologie   MeSH
• hypoxie * MeSH
• larva účinky léků   fyziologie   MeSH
• Mesocestoides účinky léků   fyziologie   MeSH
• ochranné látky farmakologie   MeSH
• silibinin farmakologie   MeSH
• silymarin farmakologie   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Exposure to solar radiation is a major cause of environmental human skin damage. The main constituent of solar UV light is UVA radiation (320-400 nm); however, the need for protection against UVA has been marginalized for a long time. As a result, there is still a lack of useful agents for UVA protection. In this study, the effect of silymarin (SM) and its main constituent silybin (SB) pre-treatment on UVA-stimulated damage to primary human dermal fibroblasts were carried out. The cells were pre-treated for 1 h with SB or SM and then were exposed to UVA light, using a solar simulator. The effect of SB and SM on reactive oxygen species (ROS) and glutathione (GSH) level, caspase-3 activity, single-strand breaks (SSB) formation and protein level of matrix metalloproteinase-1 (MMP-1), heme oxygenase-1 (HO-1), and heat shock protein (HSP70) was evaluated. Treatment with both SM and SB resulted in a reduction in UVA-stimulated ROS generation and SSB production, as well as in the prevention of GSH depletion, a decrease in the activation of caspase-3 and protein level of MMP-1. They also moderately increased HO-1 level and reduced HSP70 level. Our data showed that both SM and SB are non-phototoxic and have UVA-photoprotective potential and could be useful agents for UV-protective dermatological preparations.

• MeSH
• fibroblasty účinky léků   patologie   účinky záření   MeSH
• glutathion metabolismus   MeSH
• hemoxygenasa-1 metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kultivované buňky MeSH
• kůže patologie   účinky záření   MeSH
• lidé MeSH
• matrixová metaloproteinasa 1 metabolismus   MeSH
• poškození DNA MeSH
• primární buněčná kultura MeSH
• proteiny tepelného šoku HSP70 metabolismus   MeSH
• radiační poranění farmakoterapie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• silibinin MeSH
• silymarin terapeutické užití   MeSH
• sluneční záření MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This article aims to review critically literature published mainly within this millennium on the new and emerging applications of silymarin, the polyphenolic fraction from the seeds of Silybum marianum and its main component silybin. Silymarin and silybin used so far mostly as hepatoprotectants were shown to have other interesting activities as e.g., anticancer and canceroprotective. These activities were demonstrated in a large variety of illnesses of different organs as e.g., prostate, lungs, CNS, kidneys, pancreas and others. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new activities based on the specific receptor interaction were discovered--e.g., inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors and some others. New derivatives of silybin open new ways to its therapeutic applications. Pharmacology dealing with optically pure silybin diastereomers may suggest new mechanisms of its action.

• MeSH
• fytoterapie MeSH
• léčivé rostliny chemie   MeSH
• lidé MeSH
• ostropestřec mariánský MeSH
• rostlinné extrakty chemie   farmakologie   terapeutické užití   MeSH
• semena rostlinná chemie   MeSH
• silymarin chemie   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• antiflogistika terapeutické užití   MeSH
• antikarcinogenní látky terapeutické užití   MeSH
• antioxidancia terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• cholagoga a choleretika terapeutické užití   MeSH
• financování organizované MeSH
• fytogenní protinádorové látky terapeutické užití   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• kardiotonika terapeutické užití   MeSH
• lidé MeSH
• nádory plic prevence a kontrola   MeSH
• nádory prostaty farmakoterapie   MeSH
• nemoci zvířat farmakoterapie   MeSH
• P-glykoprotein účinky léků   MeSH
• receptory pro estrogeny účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• silymarin terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Silybin (a flavonolignan, the main component of silymarin, an extract from the seeds of Silybum marianum) has been used to date mostly as a hepatoprotectant. However, it also has other interesting activities, e.g., anticancer and hypocholesterolemic effects. It is also known that silybin can inhibit the activities of the cytochrome P450 (P450) enzymes. In this study, a weak interaction of silybin with human microsomal CYP2E1, 2A6, 2B6, 2C19, and 2D6 (IC(50) > or = 250 microM) was found; a moderate inhibition was observed for CYP1A2 and 2C8. The most prominent inhibition effect was found with CYP3A4 and CYP2C9 (IC(50) < or = 50 microM). Using mass spectometry detection, production of O-demethylated (the main metabolite) as well as hydroxylated derivatives of silybin formed by P450 enzymes was detected. The effect of different P450 inhibitors on the formation of O-demethylated product was also studied. In particular, a relatively specific inhibitor of CYP2C8 (quercetin) markedly inhibited the formation of this metabolite. With the help of recombinant enzymes (bactosomes), it was confirmed that the CYP2C8 enzyme is responsible for the reaction leading to O-demethylated silybin.

• MeSH
• antioxidancia farmakologie   metabolismus   MeSH
• aromatické hydroxylasy antagonisté a inhibitory   genetika   metabolismus   MeSH
• cytochrom P-450 CYP1A2 genetika   metabolismus   MeSH
• cytochrom P-450 CYP3A MeSH
• Escherichia coli genetika   metabolismus   MeSH
• financování organizované MeSH
• inhibitory cytochromu P450 CYP1A2 MeSH
• inhibitory cytochromu P450 MeSH
• inhibitory enzymů farmakologie   metabolismus   MeSH
• jaterní mikrozomy enzymologie   metabolismus   účinky léků   MeSH
• katalýza účinky léků   MeSH
• lidé MeSH
• molekulární struktura MeSH
• oxid uhelnatý farmakologie   MeSH
• quercetin farmakologie   MeSH
• rekombinantní proteiny metabolismus   MeSH
• silymarin farmakologie   chemie   metabolismus   MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH

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.

• Publikační typ
• časopisecké články MeSH