RESUMO
Extracts prepared from the seeds of the medicinal plant milk thistle [Silybum marianum (L.) Gaertn. (Asteraceae)] are widely used as dietary supplements due to anti-inflammatory, antitumor, and hepatoprotective effects. Called silymarin, the main components of lipophilic extracts of milk thistle seeds are flavonoids and flavonolignans including silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, taxifolin, and 2,3-dehydrosilybins. The aim of this study was to develop a method based on UHPLC-MS/MS for the chemical authentication and standardization of milk thistle silymarin. Validation included the method of standard addition to account for the lack of a blank matrix. Potential matrix effects were investigated by analyzing silymarin standards dissolved only in the initial UHPLC mobile phase. Measurements of six flavonolignans and taxifolin in the milk thistle extract using UHPLC-MS/MS with standard addition or external standard calibration produced similar results for all analytes except silydianin and 2,3-dehydrosilybin B, which showed significant peak enhancement during negative ion electrospray due to botanical matrix effects. The UHPLC-MS/MS-based method of standard addition requires <10 min per injection and is suitable for the standardization of silymarin from milk thistle in support of preclinical and clinical studies of safety and efficacy.
Assuntos
Extratos Vegetais , Silybum marianum , Silimarina , Espectrometria de Massas em Tandem , Silybum marianum/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Extratos Vegetais/análise , Silimarina/análise , Silimarina/química , Silimarina/análogos & derivados , Reprodutibilidade dos Testes , Flavonolignanos/análise , Flavonolignanos/química , Flavonolignanos/normas , Padrões de Referência , Limite de Detecção , Quercetina/análogos & derivadosRESUMO
Milk thistle is one of the most popular ingredients in the liver protection products market. Silymarin is the main component of milk thistle and contains multiple isomers. There have been few studies focusing on the compositional ratios of silymarin isomers. In this study, we developed an HPLC method for the separation and quantification of silymarin isomers, thereby elucidating their compositional ratios. Through the analysis of more than 40 milk thistle extract products on the market, we found that the ratios, specifically Ratio 1 (the silybin B content to the silybin A content, SBNB/SBNA) and Ratio 2 (the sum of the contents of silybin B and isosilybin B to the sum of the contents of silybin A and isosilybin A, (SBNB + IBNB)/(SBNA + IBNA)), are highly consistent across milk thistle extracts, averaging approximately 1.58 and 1.28, respectively. Furthermore, such ratios were verified in milk thistle seed samples. This study introduces significant findings concerning the stable ratios among silymarin isomers in milk thistle extracts and seeds, thereby offering an innovative approach for quality assurance of milk thistle extracts.
Assuntos
Flavonolignanos , Extratos Vegetais , Silibina , Silybum marianum , Silimarina , Silybum marianum/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Extratos Vegetais/análise , Silimarina/análise , Silimarina/química , Flavonolignanos/análise , Flavonolignanos/química , Silibina/análise , Silibina/química , Isomerismo , Sementes/químicaRESUMO
A new flavonolignan, sonyamandin (1), along with other known compounds was isolated from the aerial parts and seeds extracts of Silybum marianum (milk thistle) collected from Jordan. The known ones are ursolic acid (2), oleanolic acid (3), maslinic acid (4), oleic acid (5), ß-sitosterol (6), ß-, sitosteryl glucoside (7), apigenin (8), kaempferol-3-O-rhamnoside (9), apigenin-7-O-ß-D-glycoside (10), isosylibin A (11), isosylibin B (12), and silybin B (13). The absolute stereochemistry of 1 was confirmed by 2D NMR and CD analysis.
Assuntos
Flavonolignanos , Silybum marianum , Silybum marianum/química , Estrutura Molecular , Flavonolignanos/química , Flavonolignanos/isolamento & purificação , Jordânia , Sementes/química , Ressonância Magnética Nuclear Biomolecular , Sitosteroides/química , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/isolamento & purificação , Apigenina/química , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
BACKGROUND: Flavonolignans like silybin, hydnocarpin, and siliandrin are a group of natural compounds combining the structural moieties of flavonoid and phenylpropanoid (lignan). Hydnocarpin and silandrin have been less explored because of their trace occurrence in nature. OBJECTIVE: The present study aimed at chemical conversion of silybin to hydnocarpin and siliandrin. Another objective was to synthesize a series of amide derivatives and biologically evaluate them with regard to their anti-cancer effects. METHODS: In order to selectively convert silybin to 23-iodo silybin, 23-iodo hydnocarpin D and 23- iodo isosilandrin, the ratio of Ph3P, imidazole and molecular iodine was meticulously adjusted. These three iodide compounds were converted into amide compounds by chemical transformation. MTT method was applied to evaluate their anti-cancer potency. The binding affinity to related proteins was calculated by molecular docking. RESULTS: A total of 45 new amido-derivatives were synthesized and structurally characterized by NMR and HRMS. Some of them showed moderate to good antiproliferative potency against cancer cells. The activity of compound 10j was further testified by colony formation assay and molecular docking. CONCLUSION: The synthesis of 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin from silybin was successfully accomplished by one simple iodination reaction. Some of the amide derivatives of sylibin/hydnocarpin D /silandrin exhibited a remarkable inhibitory effect of proliferation on cancer cells compared to silybin. These results would pave the way for further investigation on the derivatives of flavonolignans for the treatment of cancer.
Assuntos
Antineoplásicos/farmacologia , Flavonolignanos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Flavonolignanos/síntese química , Flavonolignanos/química , Humanos , Estrutura MolecularRESUMO
The fruit of Hippophae rhamnoides L. has been used for centuries in Europe and Asia as a food with high nutritional and medicinal values. In this study, a bioactivity-guided phytochemical investigation of H. rhamnoides L. has resulted in four new dimethylallylated flavonolignans (1-4), four new isopropylpentenone-flavonolignan heterodimers (5-8), two new geranylated flavonolignans (9 and 10), and 14 known flavonolignan derivatives (11-24); they were elucidated by their spectrometric and spectroscopic methods, including HR-ESI-MS, NMR, IR, and UV from the fruit of H. rhamnoides L. for the first time. Among them, compounds 2, 5, 6, 20, and 21 showed potent immunosuppressive activities with IC50 values from 19.42 ± 3.91 to 48.05 ± 12.56 µM. Meanwhile, compounds 1, 4, 11, 12, and 13 showed moderate neuroprotective activities, which increased the cell survival rate from 50.30 ± 4.24% for the model group to 71.63 ± 3.04%, 70.02 ± 4.13%, 61.53 ± 5.93%, 61.08 ± 3.58%, and 65.68 ± 4.88% at 10 µM, respectively. The hypothetical biogenetic pathway and preliminary structure-activity relationship were found and discussed scientifically.
Assuntos
Flavonolignanos/química , Hippophae/química , Imunossupressores/química , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flavonolignanos/farmacologia , Frutas/química , Humanos , Imunossupressores/farmacologia , Estrutura Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
BACKGROUND: The small chemical class of flavonolignans encompasses unique hybrid molecules with versatile biological activities. Their anticancer effects have received considerable attention, and a large body of supporting evidence has accumulated. Moreover, their ability to interact with proteins involved in drug resistance, and to enhance the effects of conventional chemotherapeutics in decreasing cell viability make them influential partners in addressing cancer. OBJECTIVE: The review provides an outline of the various ways in which flavonolignans advance the combat against cancer. While the main focus falls on flavonolignans from milk thistle, attention is drawn to the yet, underexplored potential of less known flavonolignan subgroups derived from isoflavonoids and aurones. METHODS: Proceeding from the presentation of natural flavonolignan subtypes and their occurrence, the present work reviews these compounds with regard to their molecular targets in cancer, anti-angiogenetic effects, synergistic efficacy in conjunction with anticancer agents, reversal of drug resistance, and importance in overcoming the side effects of anticancer therapy. Recent advances in the endeavor to improve flavonolignan bioavailability in cancer are also presented. CONCLUSIONS: Significant progress has been achieved in detailing the molecular mechanisms of silybin and its congeners in experimental models of cancer. The availability of novel formulations with improved bioavailability, and data from phase I clinical trials in cancer patients provide an encouraging basis for more extensive trials aimed at evaluating the benefits of Silybum flavonolignans in cancer management. On the other hand, further research on the antitumor efficacy of iso-flavonolignans and other subtypes of flavonolignans should be pursued.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonolignanos/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Flavonolignanos/química , Humanos , Silybum marianum/química , Estrutura Molecular , Neoplasias/patologiaRESUMO
A series of novel flavonolignans were synthesized by the reaction between a lignan named samin (1) and a range of flavonoids. This simple and rapid approach allowed direct assembly of these two bulky motifs in good yields without the formation of byproducts. Upon evaluation of antidiabetic activity of the synthesized products, epicatechinosamin (ß-2g) was the most active α-glucosidase inhibitor toward maltase and sucrase. The kinetic study indicated that ß-2 g inhibited the enzymes in a mixed manner of competitive and noncompetitive inhibition.
Assuntos
Flavonolignanos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonolignanos/química , Radicais Livres/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Cinética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , alfa-Glucosidases/metabolismoRESUMO
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.
Assuntos
Aorta/efeitos dos fármacos , Flavonolignanos/química , Flavonolignanos/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Animais , Humanos , Masculino , Estrutura Molecular , Ratos , VasodilatadoresRESUMO
Hydnocarpin (Hy) is a flavonoid isolated and purified from the seeds of Hydnocarpus wightiana Blume. Herein, we have developed a built-in semi-synthetic modification on Hy by one-pot multi-component reaction and a [3 + 2] cycloaddition strategy to append five membered isoxazole and isoxazolone as new phytochemical entities (NPCEs). Two selected NPCEs viz Hy-ISO-VIII and Hy-ISO-G from the library of 20 newly synthesized derivatives after in vitro screening unveiled promising cytotoxicity and induced caspase-mediated apoptosis against the human lung and melanoma cancer cells which were well supported by virtual screening based on ligand binding affinity and molecular dynamic simulations. As a new insight, we introduced surface-enhanced Raman spectroscopy to identify the chemo-marker molecular fingerprint to confirm the cellular uptake, cytochrome c release, and DNA fragmentation in a label-free manner. The present findings throw up a surfeit of seminal reasons behind the semi-synthetic modification of Hy, stepping forward to cancer chemotherapy.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Citocromos c/antagonistas & inibidores , Flavonolignanos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Reação de Cicloadição , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonolignanos/síntese química , Flavonolignanos/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Melanoma/metabolismo , Melanoma/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Silymarin flavonolignans are well-known agents that typically possess antioxidative, anti-inflammatory, and hepatoprotective functions. Recent studies have also documented the antiviral activities of silymarin and its derivatives against several viruses, including the flaviviruses (hepatitis C virus and dengue virus), togaviruses (Chikungunya virus and Mayaro virus), influenza virus, human immunodeficiency virus, and hepatitis B virus. This review will describe some of the latest preclinical and clinical studies detailing the antiviral profiles of silymarin and its derivatives, and discuss their relevance for antiviral drug development.
Assuntos
Antivirais/farmacologia , Flavonolignanos/farmacologia , Silimarina/farmacologia , Antivirais/química , Vírus Chikungunya/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Flavivirus/efeitos dos fármacos , Flavonolignanos/química , HIV/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Silimarina/química , Togaviridae/efeitos dos fármacosRESUMO
Silybum marianum (L.) is a medicinal plant traditionally used in treatment of liver disorders. In last decades, silymarin (SM), a standardized extract from S. marianum seeds has been studied for its dermatological application, namely for UVB-protective properties. However, information on SM and its polyphenols effect on activity of enzymes participating in the (photo)aging process is limited. Therefore, evaluation of SM and its flavonolignans potential to inhibit collagenase, elastase, and hyaluronidase in tube tests was the goal of this study. The antioxidant and UV screening properties of SM and its flavonolignans silybin, isosilybin, silydianin, silychristin and 2,3-dehydrosilybin (DHSB) were also evaluated by a DPPH assay and spectrophotometrical measurement. DHSB showed the highest ability to scavenge DPPH radical and also revealed the highest UVA protection factor (PF-UVA) that corresponds with its absorption spectrum. SM and studied flavonolignans were found to exhibit anti-collagenase and anti-elastase activity. The most potent flavonolignan was DHSB. None of studied flavonolignans or SM showed anti-hyaluronidase activity. Our results suggest that SM and its flavonolignans may be useful agents for skin protection against the harmful effects of full-spectrum solar radiation including slowing down skin (photo)aging.
Assuntos
Flavonolignanos/química , Extratos Vegetais/química , Silimarina/química , Pele/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Flavonolignanos/isolamento & purificação , Humanos , Silybum marianum/química , Sementes/química , Silimarina/isolamento & purificação , Pele/patologia , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
Silymarin, the standardized extract from the milk thistle (Silybum marianum), is composed mostly of flavonolignans and is approved in the EU for the adjuvant therapy of alcoholic liver disease. It is also used for other purported effects in miscellaneous nutraceuticals. Due to polyhydroxylated structures and low systemic bioavailability, these flavonolignans are likely to interact with transition metals in the gastrointestinal tract. The aim of this study was to analyze the interactions of pure silymarin flavonolignans with copper and iron. Both competitive and non-competitive methods at various physiologically relevant pH levels ranging from 4.5 to 7.5 were tested. Only 2,3dehydrosilybin was found to be a potent or moderately active iron and copper chelator. Silybin A, silybin B and silychristin A were less potent or inactive chelators. Both 2,3dehydrosilybin enantiomers (A and B) were equally active iron and copper chelators, and the preferred stoichiometries were mainly 2:1 and 3:1 (2,3dehydrosilybin:metal). Additional experiments showed that silychristin was the most potent iron and copper reductant. Comparison with their structural precursors taxifolin and quercetin is included as well. Based on these results, silymarin administration most probably affects the kinetics of copper and iron in the gastrointestinal tract, however, due to the different interactions of individual components of silymarin with these transition metals, the biological effects need to be evaluated in the future in a much more complex study.
Assuntos
Cobre/química , Flavonolignanos/química , Ferro/química , Silimarina/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , EstereoisomerismoRESUMO
Silymarin, an extract from milk thistle (Silybum marianum) fruits, is consumed in various food supplements. The metabolism of silymarin flavonolignans in mammals is complex, the exact structure of their metabolites still remains partly unclear and standards are not commercially available. This work is focused on the preparation of sulfated metabolites of silymarin flavonolignans. Sulfated flavonolignans were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and p-nitrophenyl sulfate as a sulfate donor and characterized by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). Their 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging; ferric (FRAP) and Folinâ»Ciocalteu reagent (FCR) reducing activity; anti-lipoperoxidant potential; and effect on the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway were examined. Pure silybin A 20-O-sulfate, silybin B 20-O-sulfate, 2,3-dehydrosilybin-20-O-sulfate, 2,3-dehydrosilybin-7,20-di-O-sulfate, silychristin-19-O-sulfate, 2,3-dehydrosilychristin-19-O-sulfate, and silydianin-19-O-sulfate were prepared and fully characterized. Sulfated 2,3-dehydroderivatives were more active in FCR and FRAP assays than the parent compounds, and remaining sulfates were less active chemoprotectants. The sulfated flavonolignans obtained can be now used as authentic standards for in vivo metabolic experiments and for further research on their biological activity.
Assuntos
Antioxidantes/química , Flavonolignanos/química , Frutas/química , Silybum marianum/química , Suplementos Nutricionais , Sequestradores de Radicais Livres/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Plantas/química , Plantas/ultraestrutura , Sulfatos/químicaRESUMO
The physicochemical properties of classical lignans, neolignans, flavonolignans and carbohydrate-lignan conjugates (CLCs) were analysed to assess their ADMET profiles and establish if these compounds are lead-like/drug-like and thus have potential to be or act as leads in the development of future therapeutics. It was found that while no studied compounds were lead-like, a very large proportion (>75%) fulfilled all the requirements to be deemed as present in drug-like space and almost all compounds studied were in the known drug space. Principal component analysis was an effective technique that enabled the investigation of the relationship between the studied molecular descriptors and was able to separate the lignans from their sugar derivatives and flavonolignans, primarily according to the parameters that are considered when defining chemical space (i.e., number of hydrogen bond donors, acceptors, rotatable bonds, polar surface area and molecular weight). These results indicate that while CLCs and flavonolignans are less drug-like, lignans show a particularly high level of drug-likeness, an observation that coupled with their potent biological activities, demands future pursuit into their potential for use as therapeutics.
Assuntos
Flavonolignanos/química , Lignanas/química , Ligação de Hidrogênio , Estrutura Molecular , Peso Molecular , Análise de Componente PrincipalRESUMO
A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22â¯cells. Despite weak activities in the FRAP assay, esters of the α,ß-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12â¯cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aß42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.
Assuntos
Antioxidantes/farmacologia , Ésteres/farmacologia , Flavonolignanos/farmacologia , Fármacos Neuroprotetores/farmacologia , Silimarina/farmacologia , Peptídeos beta-Amiloides , Animais , Antioxidantes/síntese química , Antioxidantes/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Ésteres/síntese química , Ésteres/química , Flavonolignanos/química , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Células PC12 , Agregados Proteicos/efeitos dos fármacos , Ratos , Silibina , Silimarina/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
In recent years, there has been increasing interest in dimeric molecules due to reports of their promising therapeutic value in the treatment of numerous diseases (such as cancer, HIV, Alzheimer's and, malaria). Many reports in the literature have highlighted the ability of these molecules to interact not only with specific biologic receptors but also to induce a biological response that more than doubles the results of the corresponding monomeric counterpart. In this regard, flavonolignan dimers or simply bi-flavonolignans are an emerging class of dimeric compounds that unlike bi-flavonoids, which are very widespread in nature, consist of synthetic dimers of some flavonolignans isolated from the milk thistle Silybum marianum [L. Gaertn. (Asteraceae)]. This mini-review will discuss recent developments in the synthesis, characterization and antioxidant activity of new families of flavonolignan dimers, in light of emerging medicinal chemistry strategies.
Assuntos
Dimerização , Flavonolignanos/química , Técnicas de Química Sintética , Flavonolignanos/síntese química , Flavonolignanos/classificação , Humanos , Silybum marianum/química , Estrutura Molecular , Silibina/químicaRESUMO
The extract from milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin, contains a variety of flavonolignans and displays antioxidant, anti-inflammatory, immunomodulatory and hepatoprotective properties. As silybin is the main component of silymarin, the literature mainly focuses on this compound, ignoring all other components. This leads to problems in reproducibility of scientific results, as the exact composition of silymarin is often unknown and can vary to a certain degree depending on the processing, chemo-variety of the plant used and climatic conditions during the plant growth. There are studies dealing with the analytical separation and quantification of silymarin components as well as studies focused on silymarin content in clinically used drugs, in various plant parts, seasons, geographic locations etc. However, no comparison of detail flavonolignan profiles in various silymarin preparations is available to date. Also, as a result of the focus on the flavonolignans; the oil fraction, which contains linoleic, oleic and palmitic acids, sterols, tocopherol (vitamin E) and phospholipids, has been neglected. Due to all these factors, the whole plant is used e.g. as animal feed, the leaves can be eaten in salads and seed oil, besides culinary uses, can be also utilized for biodiesel or polymer production. Various HPLC separation techniques for the determination of the content of the flavonolignans have been vastly summarized in the present review.
Assuntos
Anti-Inflamatórios/análise , Antioxidantes/análise , Fatores Imunológicos/análise , Extratos Vegetais/química , Sementes/química , Silimarina/química , Anti-Inflamatórios/química , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Flavonolignanos/análise , Flavonolignanos/química , Fatores Imunológicos/química , Extratos Vegetais/análise , Silibina/análise , Silibina/química , Silimarina/análiseRESUMO
The electrochemical oxidation of the natural antioxidant 2,3-dehydrosilybin (DHS) was investigated in acetonitrile. The spectral changes during two electron and two proton oxidation registered by in situ IR spectroelectrochemistry show that the electron transfer is followed by a subsequent chemical reaction with traces of water. A benzofuranone derivative (BF) is formed by ECEC (electron transfer-chemical reaction-electron transfer-chemical reaction) process at the potential of the first oxidation wave. A minor difference in the chemical structures of flavonolignans DHS and silybin, the presence of a double bond between atoms C-2 and C-3 in the DHS molecule, causes the formation of completely different oxidation products. BF was for the first time identified as the product of the oxidation of flavonolignan DHS. Its formation was proved by electroanalytical, chromatographic, and spectroelectrochemical techniques. Molecular orbital calculations support the experimental findings.
Assuntos
Técnicas Eletroquímicas , Flavonolignanos/química , Silimarina/química , Transporte de Elétrons , Teoria Quântica , Silibina , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Flavonolignans constitute an important class of plant secondary metabolites formed by oxidative coupling of one flavonoid and one phenylpropanoid moiety. The standardized flavonolignan-rich extract prepared from the fruits of Silybum marianum is known as silymarin and has long been used medicinally, prominently as an antihepatotoxic and as a chemopreventive agent. Principal component analysis of the variation in flavonolignan content in S. marianum samples collected from different locations in Egypt revealed biosynthetic relationships between the flavonolignans. Silybin A, silybin B, and silychristin are positively correlated as are silydianin, isosilychristin, and isosilybin B. The detection of silyamandin in the extracts of S. marianum correlates with isosilychristin and silydianin content. The positive correlation between silydianin, isosilychristin, and silyamandin was demonstrated using quantitative 1H nuclear magnetic resonance spectroscopy (qHNMR). These correlations can be interpreted as evidence for the involvement of a flavonoid radical in the biosynthesis of the flavonolignans in S. marianum. The predominance of silybins A & B over isosilybin A & B in the silybin-rich samples is discussed in light of the relative stabilities of their respective radical flavonoid biosynthetic intermediates.
Assuntos
Flavonolignanos/biossíntese , Flavonolignanos/química , Silybum marianum/química , Silimarina/química , Egito , Frutas/química , Estrutura Molecular , Metabolismo Secundário , Silibina , Silimarina/análogos & derivadosRESUMO
Two new compounds a flavanolignan (1), and an alkane (2) along with four known compounds including two fatty acid esters (3-4) and two isocoumarins (5-6) were isolated from the methanolic extract of the stem bark of Newtonia griffoniana. Their structures were elucidated using spectroscopic methods including extensive 1-D and 2-D NMR experiments.