Search

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. [ABSTRACT FROM AUTHOR]

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), β-sitosterol (6), β-, sitosteryl glucoside (7), apigenin (8), kaempferol-3-O-rhamnoside (9), apigenin-7-O-β-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. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum Linn.; Poaceae) is the second most cultivated food crop among all global cereal crop production. The high carbohydrate content of its grains provides energy, multiple nutrients, and dietary fiber. After threshing, a substantial amount of wheat hull is produced, which serves as the non-food component of wheat. For the valorization of these by-products as a new resource from which functional components can be extracted, the hull from the seeds of cultivated wheat mutant lines bred after γ-irradiation were collected. Untargeted metabolite analysis of the hull of the original cultivar (a crossbreeding cultivar., Woori-mil × D-7) and its 983 mutant lines were conducted using ultra-performance liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry technique. A total of 55 molecules were tentatively identified, including 21 compounds found in the Triticum species for the first time and 13 compounds not previously described. Among them, seven flavonolignans with a diastereomeric structure, isolated as a single compound from the hull of T. aestivum in our previous study, were used as the standards in the metabolite analysis. The differences in their collision cross-section values were shown to contribute to the clear distinction between tricine-lignan stereoisomers. To select functionally active agents with anti-inflammatory activity among the identified compounds, the wheat hull samples were evaluated for their inhibitory effect on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. As a result of multivariate analysis based on the results of chemical and biological profiles of the wheat hull samples, 10 metabolites were identified as key markers, contributing to the distinction between active and inactive mutant lines. Considering that one of the four key markers attributed to anti-inflammatory activity has been identified to be a flavonolignan, the wheat hull could be a valuable source of diverse tricin-lignan type compounds and used as a natural health-promoting product in food supplements.

Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure–activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation. [ABSTRACT FROM AUTHOR]

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (<2 min). The formulation showed good matrix integrity and retarded the release of drug for >12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time. [ABSTRACT FROM AUTHOR]

Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure–activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation.

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time.

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.

Milk thistle ( Silybum marianum ) is well-known for its antioxidant activity due to the presence of silymarin. Albeit some studies show a potential for skin inflammation, its activity against dermal MMP-9 and MMP-2 remains to be studied. Silymarin isolated from an S. marianum herbal extract was tested for gelatinase inhibition in the presence of isolated MMP-9 and in dermal adenocarcinome HaCaT cells. Silymarin was then further tested in vivo , using a cutaneous inflammation mice model mediated by reactive oxygen species. Silymarin was able to significantly inhibit gelatinolytic activity in vitro without impairing cell growth and viability. Furthermore, inhibition was more pronounced in cells than with the isolated gelatinase, suggesting an additional effect upon metabolic pathways. In vivo , silymarin was able to reduce ear edema up to 74% and attenuated histological lesions. Results highlight silymarin potential for application in skin inflammatory disorders via gelatinase inhibition.

The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans - silybin, silychristin and silydianin - 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin ( 7 ) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin ( 7 ) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.

Wheat (Triticum aestivum Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, T. aestivum hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (1) and seven flavonolignans (2–8). Compounds 2–8 have not yet been isolated from Triticum species. All compounds were evaluated for their LPS-induced NO production inhibition, and 1, 2, 4, 6, and 8 exhibited inhibitory effects with IC50 values ranging from 24.14 to 58.95 μM. These results suggest the potential of using T. aestivum hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product. [ABSTRACT FROM AUTHOR]

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 (β-2g) was the most active α-glucosidase inhibitor toward maltase and sucrase. The kinetic study indicated that β-2 g inhibited the enzymes in a mixed manner of competitive and noncompetitive inhibition. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase 1B (PTP1B) is an attractive molecular target for anti-diabetes, anti-obesity, and anti-cancer drug development. From the seeds of Silybum marianum, nine flavonolignans, namely, silybins A, B (1, 2), isosilybins A, B (3, 4), silychristins A, B (5, 6), isosilychristin A (7), dehydrosilychristin A (8), and silydianin (11) were identified as a novel class of natural PTP1B inhibitors (IC50 1.3 7–23.87 µM). Analysis of structure–activity relationship suggested that the absolute configurations at C-7" and C-8" greatly affected the PTP1B inhibitory activity. Compounds 1–5 were demonstrated to be non-competitive inhibitors of PTP1B based on kinetic analyses. Molecular docking simulations resulted that 1–5 docked into the allosteric site, including α3, α6, and α7 helix of PTP1B. At a concentration inhibiting PTP1B completely, compounds 1–5 moderately inhibited VHR and SHP-2, and weakly inhibited TCPTP and SHP-1. These results suggested the potentiality of these PTP1B inhibitors as lead compounds for further drug developments.

Quantitative correlations between the contents of the flavonolignans silychristin A and silybins A/B provide biosynthetic clues that support a pathway in which one mesomeric form of a taxifolin radical is undergoing an oxidative coupling with a coniferyl alcohol radical. The flavonolignan content and patterns reported in the literature for 53 samples, representing populations of the Silybum marianum plant growing in different parts of the world, were subject to a meta-analysis. Linear regression analyses were carried out on these data sets, and a mathematical model was derived that predicts the content of silychristin A relative to the metabolomic pattern of its congeners. The validity of the model was verified by applying it to test samples. This approach could potentially become a tool to enhance the understanding of both the relative composition of the silymarin complex and the biosynthetic pathways that underlie its formation. [ABSTRACT FROM AUTHOR]

Silymarin, a mixture of diastereomeric and regioisomeric flavonolignans from milk thistle (Silybum marianum (L.) Gaertn.) fruits, is known to possess a panel of pharmacological activities. However, due to low water solubility and extensive phase II metabolism, the oral bioavailability of the flavonolignans is limited. Since their interaction with gut microbiome is likely due to their predominantly fecal excretion route, the biotransformation of milk thistle flavonolignans by gut microorganisms was studied. A 1:1 mixture of the two main silymarin flavonolignans silybins A and B was incubated in human fecal suspension from one donor for 24 h under anoxic conditions. Purification of the incubate allowed to isolate and structurally elucidate the two main metabolites as (2 R , 3 R)-2-{4-[2-(3,4-dihydroxy-phenyl)-(1 R)-1-hydroxymethyl-ethoxy]-3-hydroxy-phenyl}-3,5,7-trihydroxy-chroman-4-one (a product of demethylation and dioxane ring cleavage) and demethylsilybin B. Furthermore, silymarin was incubated with human fecal suspension, and its biotransformation was monitored by means of LC-HRMS metabolite profiling. Apart from the two isolated and structurally elucidated metabolites, several types of biotransformation products could be annotated, including demethylation products, reduction/ring cleavage products, products of demethylation plus reduction/ring cleavage, as well as several low molecular weight aromatic metabolites. The potential pharmacological activities of these gut microbial metabolites deserve closer examination in the future. [Display omitted] • Milk thistle flavonolignans were biotransformed by fecal microbiota in vitro • Four different series of microbial flavonolignan metabolites were detected • Two biotransformation products of silybins A and B were isolated and elucidated [ABSTRACT FROM AUTHOR]

The Silybum marianum (L.) Gaertn. is the dicotyledonous herbs of the Asteraceae family that is important in medical industry. The biological active compound of S. marianum is a mixture of several flavonolignals generally known as silymarin. The purpose of this study was to optimize S. marianum tissue culture for callus induction, silymarin production and comparison of some biochemical traits between explants and its derived callus. In this experimental study, the seeds were surface sterilized and transferred to MS medium to achieve sterile seedlings. Then, the effects of different concentrations of 2,4-D either alone or in combination with Kin were investigated on callus induction and silymarin production of root and leaf explants from sterile seedlings. The experiment was performed in complete randomized design with three replicates. The results revealed that the highest percentage of callus induction and silymarin accumulation (14.4%) were observed with 0.5 and 1 mg/L 2,4-D and Kin in root explant after one month. The quantitative and qualitative data from HPLC method revealed that the major flavonolignans in the root and its derived callus was isosilybin B (ISBNB). But the main component in leaf explant and its derived callus was silydianin (SDN). The results showed that silymarin level in root and leaf explants was lower than their derived callus. Meanwhile lignin amount in the root and leaf explants was much higher than corresponding callus. In addition, peroxidase activity was significantly higher in callus derived from root explant, compared to leaf explant and its derived callus. The current data demonstrated that callus derived from root explants can be an efficient source for silymarin production.

Wheat ( Triticum aestivum Linn.; Poaceae) is the second most cultivated food crop among all global cereal crop production. The high carbohydrate content of its grains provides energy, multiple nutrients, and dietary fiber. After threshing, a substantial amount of wheat hull is produced, which serves as the non-food component of wheat. For the valorization of these by-products as a new resource from which functional components can be extracted, the hull from the seeds of cultivated wheat mutant lines bred after γ-irradiation were collected. Untargeted metabolite analysis of the hull of the original cultivar (a crossbreeding cultivar., Woori-mil × D-7) and its 983 mutant lines were conducted using ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry technique. A total of 55 molecules were tentatively identified, including 21 compounds found in the Triticum species for the first time and 13 compounds not previously described. Among them, seven flavonolignans with a diastereomeric structure, isolated as a single compound from the hull of T. aestivum in our previous study, were used as the standards in the metabolite analysis. The differences in their collision cross-section values were shown to contribute to the clear distinction between tricine-lignan stereoisomers. To select functionally active agents with anti-inflammatory activity among the identified compounds, the wheat hull samples were evaluated for their inhibitory effect on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. As a result of multivariate analysis based on the results of chemical and biological profiles of the wheat hull samples, 10 metabolites were identified as key markers, contributing to the distinction between active and inactive mutant lines. Considering that one of the four key markers attributed to anti-inflammatory activity has been identified to be a flavonolignan, the wheat hull could be a valuable source of diverse tricin-lignan type compounds and used as a natural health-promoting product in food supplements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Kil, Ryoo, Jin, Hong, Kim, Jung, Nam and Han.)

The exposure of naked unprotected skin to solar radiation may result in numerous acute and chronic undesirable effects. Evidence suggests that silymarin, a standardized extract from Silybum marianum (L.) Gaertn. seeds, and its major component silybin suppress UVB-induced skin damage. Here, we aimed to investigate the UVA-protective effects of silymarinʼs less abundant flavonolignans, specifically isosilybin (ISB), silychristin (SC), silydianin (SD), and 2,3-dehydrosilybin (DHSB). Normal human dermal fibroblasts (NHDF) pre-treated for 1 h with flavonolignans were then exposed to UVA light using a solar simulator. Their effects on reactive oxygen species (ROS), carbonylated proteins and glutathione (GSH) level, caspase-3 activity, single-strand breaks' (SSBs) formation and protein level of matrix metalloproteinase-1 (MMP-1), heme oxygenase-1 (HO-1), and heat shock protein (HSP70) were evaluated. The most pronounced preventative potential was found for DHSB, a minor component of silymarin, and SC, the second most abundant flavonolignan in silymarin. They had significant effects on most of the studied parameters. Meanwhile, a photoprotective effect of SC was mostly found at double the concentration of DHSB. ISB and SD protected against GSH depletion, the generation of ROS, carbonylated proteins and SSBs, and caspase-3 activation, but had no significant effect on MMP-1, HO-1, or HSP70. In summary, DHSB and to a lesser extent other silymarin flavonolignans are potent UVA-protective compounds. However, due to the in vitro phototoxic potential of DHSB published elsewhere, further studies are needed to exclude phototoxicity for humans as well as to confirm our results on human skin ex vivo and in vivo. [ABSTRACT FROM AUTHOR]

In this study, a new flavonolignan vernicilignan A was isolated from Toxicodendron vernicifluum. The neuroprotective effects of this compound against H 2 O 2 induced cell injury in SH-SY5Y cells were evaluated by MTT assay and LDH release assay. Vernicilignan A dose-dependently attenuated the cell injury and LDH release induced by H 2 O 2 in SH-SY5Y cells. Further study indicated that vernicilignan A reduced cell apoptosis caused by H 2 O 2 treatment via regulation of some apoptotic related proteins including Bax, Bcl-2, caspase 3 and caspase 9. Also, vernicilignan A increase the cell viability of H 2 O 2 treated cells via the activation of Akt and GSK3β. Base on the findings, vernicilignan A exhibited neuroprotective effects through the activation of PI3K/Akt signaling and inhibition of mitochondria apoptosis pathway. Vernicilignan A might be a promising therapeutic agent for oxidative stress induced neurodegenerative diseases. Unlabelled Image [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase 1B (PTP1B) is an attractive molecular target for anti-diabetes, anti-obesity, and anti-cancer drug development. From the seeds of Silybum marianum, nine flavonolignans, namely, silybins A, B (1, 2), isosilybins A, B (3, 4), silychristins A, B (5, 6), isosilychristin A (7), dehydrosilychristin A (8), and silydianin (11) were identified as a novel class of natural PTP1B inhibitors (IC50 1.3 7-23.87 µM). Analysis of structure-activity relationship suggested that the absolute configurations at C-7" and C-8" greatly affected the PTP1B inhibitory activity. Compounds 1-5 were demonstrated to be non-competitive inhibitors of PTP1B based on kinetic analyses. Molecular docking simulations resulted that 1-5 docked into the allosteric site, including α3, α6, and α7 helix of PTP1B. At a concentration inhibiting PTP1B completely, compounds 1-5 moderately inhibited VHR and SHP-2, and weakly inhibited TCPTP and SHP-1. These results suggested the potentiality of these PTP1B inhibitors as lead compounds for further drug developments. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, T. aestivum hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (1) and seven flavonolignans (2–8). Compounds 2–8 have not yet been isolated from Triticum species. All compounds were evaluated for their LPS-induced NO production inhibition, and 1, 2, 4, 6, and 8 exhibited inhibitory effects with IC50 values ranging from 24.14 to 58.95 μM. These results suggest the potential of using T. aestivum hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product.

Chemical investigation on the fruits of Zanthoxylum motuoense have led to the isolation of a new flavonolignan (1), together with three known flavonoids (2 - 4), as well as five alkylamides (5 – 9). Their structures were determined by NMR, IR, UV, CD spectra and HRESIMS data. The chemotaxonomic significance of these compounds was discussed. The neuroprotective activity of the isolated compounds were evaluated. Compound 6 showed a significant protective effect against corticosterone-induced neuronal damage at 20 μmol/L. [Display omitted] • Nine compounds were isolated from the fruits of Zanthoxylum Motuoense. • Compounds 1 was identified as a new flavonolignan. • All the compounds were isolated from Z. motuoense for the first time. • Alkylamides could be recognized as a typical biomarker for Zanthoxylum genus and Rutaceae family. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Divalent or multivalent molecules often show enhanced biological activity relative to the simple monomeric units. Here we present enzymatically and chemically prepared dimers of the flavonolignans silybin and 2,3-dehydrosilybin. Their electrochemical behavior was studied by in situ and ex situ square wave voltammetry. The oxidation of monomers and dimers was similar, but adsorption onto the electrode and cell surfaces was different. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) and an inhibition of microsomal lipoperoxidation assay were performed with same trend of results for silybin and 2,3-dehydrosilybin dimers. Silybin dimer showed better activity than the monomer, while on the contrary 2,3-dehydrosilybin dimer presented weaker antioxidant/antilipoperoxidant activity than its monomer. Cytotoxicity was evaluated on human umbilical vein endothelial cells, normal human adult keratinocytes, mouse fibroblasts (BALB/c 3T3) and human liver hepatocellular carcinoma cell line (HepG2). Silybin dimer was more cytotoxic than the parent compound and in the case of 2,3-dehydrosilybin its dimer showed weaker cytotoxicity than the monomer.

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.

A selective acylation protocol using cerium chloride (CeCl3) as catalyst was applied to functionalize silybinin (1), a natural antioxidant flavonolignan from milk thistle fruit, in order to increase its solubility in lipophilic media while retaining its strong antioxidant activity. The selective esterification of 1 at the position 3-OH with a palmitate acyl chain leading to the formation of the 3-O-palmitoyl-silybin (2) was confirmed by both mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. The antioxidant activity of 1 was at least retained and even increased with the CUPRAC assay designed to estimate the antioxidant activity of both hydrophilic and lipophilic compounds. Finally, the 3-O-palmitoylation of 1, resulting in the formation of 2, also increased its anti-lipoperoxidant activity (i.e., inhibition of conjugated diene production) in two different lipophilic media (bulk oil and o/w emulsion) subjected to accelerated storage test.

Objective We assessed the impacts of silymarin co-administration on aspartame-induced changes in novelty-induced behaviours, memory, anxiety-related behaviours, cerebral antioxidant status and histomorphology in mice. Method Six groups of mice were administered vehicle (distilled water), silymarin (25 mg/kg), aspartame (at 160 or 320 mg/kg), and silymarin (25 mg/kg) co-administered with aspartame at 160 or 320 mg/kg daily for 21 days, via an oral cannula. Behaviours were assessed after the first and last dose of treatment. Animals were sacrificed thereafter. Brain homogenates were used to assess antioxidant status; while sections of the cerebral cortex were processed for routine histology. Result Repeated co-administration of silymarin with aspartame resulted in significant suppression of horizontal locomotion and rearing, while grooming behaviour was enhanced; when compared to aspartame alone. Spatial working-memory showed significant improvement only after acute co-administration, while anxiety-related behaviours were reduced after repeated administration of both silymarin and aspartame. Cerebral cortical morphological integrity was better preserved, and astrocytic reactivity reduced with silymarin co-administration. Brain activity of superoxide dismutase and nitric oxide levels were decreased, while glutathione peroxidase activity was increased, when compared to levels seen with aspartame alone. Conclusion The study shows that co-administration of silymarin with aspartame was associated with significant attenuation of central effects, when compared to administration of aspartame alone. [ABSTRACT FROM AUTHOR]

In this work, the electrochemical behavior of flavonolignan silybin (SB) and 2,3-dehydrosilybin (DHSB) and their respective conjugates SB-SB and DHSB-DHSB were studied using voltammetric techniques at a glassy carbon electrode. The redox mechanism of SB and its conjugate occurs in two oxidation steps where the hydroxy groups of the guaiacyl and resorcinol moiety are involved. DHSB and its conjugate are oxidized in three subsequent steps. The enol group in DHSB and DHSB-DHSB is involved in the additional oxidation step, due to the enhanced electron-donor capacity and reactivity of the 2,3-dehydroderivatives compared to the parent flavonolignan molecule. The developed voltammetric methods were subsequently used for the analysis of flavonolignan-DNA interactions. Comparative experiments revealed a remarkable binding affinity between the flavonolignan homoconjugates and double-helical calf thymus DNA, compared to the corresponding monomeric compounds. In addition, biochemical and electrophoretic experiments revealed the flavonolignan-dsDNA binding not to involve intercalation as the major interaction mode. The same experiments have also shown that both flavonolignan conjugates inhibit the activity of type I topoisomerase, which is a DNA topology (superhelicity) modulating enzyme. We suppose that our results could be used in further studies focused on DNA flavonolignan binding and DNA processing protein inhibition by flavonolignan 2,3-dehydroderivatives. [ABSTRACT FROM AUTHOR]

Milk thistle (Silybum marianum (L.) Gaertn.) is one of the valuable medicinal plants which used in the treatment of liver disorders. The major active constituents in this plant are flavonolignans, collectively known as silymarin which is a mixture of three isomer silybin, silydianin and silycristin. Its therapeutic properties are due to the presence of silymarin. The seeds contain the highest amount of silymarin, but the other plant parts have less amount of this compound. The silymarin content in fruits depends on milk thistle variety and geographic and climatic condition. In this review, we summarized the accomplished investigations on aspects of medicinal, cultivation, biology and biotechnology of milk thistle.

The effect of new synthetic pyrazinecarboxamide derivatives as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro was investigated. Both tested elicitors increased the production of flavonolignans in S. marianum callus and suspension cultures and flavonoids in O. arvensis callus and suspension cultures. Compound I, 5-(2-hydroxybenzoyl)-pyrazine-2-carboxamide, has shown to be an effective elicitor of flavonolignans and taxifoline production in Silybum marianum culture in vitro. The maximum content of silydianin (0.11%) in S. marianum suspension culture was induced by 24 h elicitor application in concentration of 1.159 × 10−3 mol/L. The maximum content of silymarin complex (0.08%) in callus culture of S. marianum was induced by 168 h elicitor application of a concentration 1.159 × 10−4 mol/L, which represents contents of silydianin (0.03%), silychristin (0.01%) and isosilybin A (0.04%) compared with control. All three tested concentrations of compound II, N-(2-bromo-3-methylphenyl)-5-tert-butylpyrazin-2-carboxamide increased the flavonoid production in callus culture of O. arvensis in a statistically significant way. The best elicitation effect of all elicitor concentrations had the weakest c3 concentration (8.36 × 10−6 mol/L) after 168 h time of duration. The maximum content of flavonoids (about 5,900%) in suspension culture of O. arvensis was induced by 48 h application of c3 concentration (8.36 × 10−6 mol/L).

Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.

Background: Silybum marianum has been recognized as an antihepatotoxic plant. The active constituents of Silybum marianum include a group of flavonolignans known collectively as silymarin. Slymarin production by cultured cells of Silybum marianum has already been reported. Also, it was reported that physiochemical factors can influenced silymarin production in S. marinum cell cultures. Objective: Evaluation the affect of sugar source on flavonolignan production in S. marianum callus cultures. Method: Callus culture of S. marianum were established by transferring seedling on solidified MS medium supplemented with 1 mg/l 2, 4 dichlorophenoxy acetic acid and 0.2 mg/l kinetin. Optimal callus were subcultured to medium containing different concentration of sugars including fructose, glucose, and sucrose. Then cultures were harvested after 28 days, dried and extracted with methanol. Quantitative analyses of flavonolignans were carried out using spectrophotometric method. Results: Higher levels of flavonolignans accumulation were observed in cultures containing 6% of all three sugars comparing with concentrations of 3% and 1.5%. Conclusion: It seems flavonolignans production in callus culture of S. marianum influenced by concentration of sugars rather than of sugars type.