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Silybum marianum (L.) Gaertn (Asteraceae) is a well-known medicinal plant enriched with antioxidative properties beneficial for liver-related diseases. The experiment was conducted to explore the effect of different PGPs as soil-supplied mode to modulate the growth-related attributes, gas exchange parameters, and antioxidative efficiency of different milk thistle ecotypes such as Faisalabad (FSD), Gujranwala (GUJ), Quetta (QTA), and Kallar Kahar (KK) under saline stresses conditions (NaCl 120 mM/irrigation water). After salinity development, ascorbic acid (AsA), thiourea (TU), and moringa leaf extract (MLE) were soil supplied with 500 µM, 250 µM, and 3% concentrations, respectively. Data conferring the growth parameters elucidate significant reduction in all growth parameters and pigment contents under salinity stress. The effect of PGPs effectively upregulates the activity of these enzymatic antioxidants and improved salt tolerance to saline field conditions with numerous additional stresses, and the order of improvement was AsA, followed by MLE and TU. The percent increase with AsA treatment was noted as GR (34.78), DHAR (1.73), MDHAR (11.83), soluble sugar (8.78), amino acid (7.47), and free proline 15.75, while percent decrease in H2O2 content was 20.56 as compared to control plants. QTA and FSD ecotypes were observed as salt-tolerant ecotypes compared to GUJ and KK.

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John’s wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care.

Milk thistle is an oil and medicinal crop known as an alternative oil crop with a high level of unsaturated fatty acids, which makes it a favorable edible oil for use in food production. To evaluate the importance of Milk thistle lipids in drought tolerance, an experiment was performed in field conditions under three different water deficit levels (Field capacity (FC), 70% FC and 40% FC). After harvesting seeds of the plant, their oily and methanolic extracts were isolated, and subsequently, types and amounts of lipids were measured using GC–MS. Genes and enzymes engaged in biosynthesizing of these lipids were identified and their expression in Arabidopsis was investigated under similar conditions. The results showed that content of almost all measured lipids of milk thistle decreased under severe drought stress, but genes (belonged to Arabidopsis), which were involved in their biosynthetic pathway showed different expression patterns. Genes biosynthesizing lipids, which had significant amounts were selected and their gene and metabolic network were established. Two networks were correlated, and for each pathway, their lipids and respective biosynthesizing genes were grouped together. Four up-regulated genes including PXG3, LOX2, CYP710A1, PAL and 4 down-regulated genes including FATA2, CYP86A1, LACS3, PLA2-ALPHA were selected. The expression of these eight genes in milk thistle was similar to Arabidopsis under drought stress. Thus, PXG3, PAL, LOX2 and CYP86A1 genes that increased expression were selected for protein analysis. Due to the lack of protein structure of these genes in the milk thistle, modeling homology was performed for them. The results of molecular docking showed that the four proteins CYP86A1, LOX2, PAL and PXG3 bind to ligands HEM, 11O, ACT and LIG, respectively. HEM ligand was involved in production of secondary metabolites and dehydration tolerance, and HEM binding site remained conserved in various plants. CA ligands were involved in synthesis of cuticles and waxes. Overall, this study confirmed the importance of lipids in drought stress tolerance in milk thistle.

Although milk thistle oil has been authorized as a new edible oil in many countries, there is a lack of information about its chemical and biological properties. Thus, this study aimed to characterize the phospholipid and n-alkane composition as well as the α-glucosidase and cyclooxygenase inhibitory effects of milk thistle oil. The phospholipid composition of milk thistle seed oil was determined by liquid chromatography coupled to mass spectrometry HPLC–ESI–MS method and five glycerophospholipid classes were detected: phosphatidylinositol (35.8 ± 2.31%), phosphatidylcholine (29.2 ± 1.43%), phosphatidylethanolamine (15.7 ± 1.75%), phosphatidylglycerol (12.4 ± 1.61%) and phosphatidic acid (6.9 ± 0.82%). Twenty-three phospholipid molecular species were characterized, containing mainly palmitic, oleic and linoleic acids. Using gas chromatography coupled to mass spectrometry, seventeen n-alkanes were detected ranging from C14 to C35 carbon atoms. Nonacosane (13.79 ± 1.15%) was the predominant compound followed by heptacosane (9.52 ± 0.87%) and hexacosane (9.33 ± 1.21%). The carbon preference index of long-chain n-alkanes (CPI25–35) exhibited mainly odd/even predominance. The phospholipid and n-alkane composition of milk thistle oil is quite different from that of other oilseeds, indicating the possible use of those compounds as a means of determining oil authenticity. The total phenolic content of the tested oil was 10.28 ± 1.2 mg GAE/ g of oil. Furthermore, the tested oil showed moderate anti-cyclooxygenase1 capacity (IC50 = 42.3 ± 0.8 μg/mL) in comparison with the positive control aspirin. However, the inhibitory effect of milk thistle oil against α-glucosidase (IC50 = 28.4 ± 0.54 μg/mL) was similar to that of the positive control acarbose, which reveals the tested oil as a promising source of natural α-glucosidase inhibitors, proves protection against type 2 diabetes. Milk thistle oil has an excellent potential for application in the food and pharmaceutical industries.

Increased use of vancomycin for treating infections, and the associated risk of causing nephrotoxicity lead to the present study. The antioxidant and anti-apoptotic potential of Silybum marianum is used along with vancomycin to reduce adverse effects on the kidney. Vero cells (monkey kidney cells) and mice were used to test S. marianum extract on vancomycin induced nephrotoxicity. Vero cells were treated with different concentrations of vancomycin and S. marianum for 24 h for determination of cytotoxic potential and mRNA levels of apoptotic genes p53 , p21, and cyt-c were measured. For in-vivo studies mice were divided into five groups; G1 control (untreated), G2 vehicle (olive oil), G3 vancomycin treated (300 mg/kg body weight), G4 (S. marianum; 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight simultaneously) and G5 (S. marianum 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight treatment started after day 4 of S. marianum treatment). After 10 days histopathological analysis of mice kidneys was performed, serum urea and creatinine were analysed and mRNA expression of p53 , p21, and cyt-c was evaluated. Expression of p53, p21, and cyt-c in Vero cells was elevated in response to vancomycin treatment, whereas after S. marianum administration expression of these genes reduced. Vancomycin showed apoptosis in cells at the concentration of 6 mg/ml (LC50). Urea and creatinine levels in mice were increased in response to vancomycin administration and kidney histology showed an abnormality in functional units. The apoptotic cells were very visible in kidney structure in vancomycin treated group. These symptoms were however relieved in groups where treatment of S. marianum extract was given. mRNA expression of p53 , p21, and cyt-c also reduced in S. marianum treated groups of mice. S. marianum extract has protective effects against renal damage from vancomycin induced oxidative stress and relieves symptoms may be by downregulating apoptotic genes.

Silymarin, milk thistle (Silybum marianum) extract, contains a mixture of mostly isomeric bioactive flavonoids and flavonolignans that are extensively studied, especially for their possible liver-protective and anticancer effects. Because of the differing bioactivities of individual isomeric compounds, characterization of their proportion in a mixture is highly important for predicting its effect on health. However, because of silymarin's complexity, this is hardly feasible by common analytical techniques. In this work, ultraperformance liquid chromatography coupled with drift tube ion mobility spectrometry and quadrupole time-of-flight mass spectrometry was used. Eleven target silymarin compounds (taxifolin, isosilychristin, silychristins A and B, silydianin, silybins A and B, 2,3-cis-silybin B, isosilybins A and B and 2,3-dehydrosilybin) and five unknown flavonolignan isomers detected in the milk thistle extract were fully separated in a 14.5-min analysis run. All the compounds were characterized on the basis of their accurate mass, retention time, drift time, collision cross section and fragmentation spectra. The quantitative approach based on evaluation of the ion mobility data demonstrated lower detection limits, an extended linear range and total separation of interferences from the compounds of interest compared with the traditional approach based on evaluation of liquid chromatography-quadrupole time-of-flight mass spectrometry data. The following analysis of a batch of milk thistle-based food supplements revealed significant variability in the silymarin pattern, especially in the content of silychristin A and silybins A and B. This newly developed method might have high application potential, especially for the characterization of materials intended for bioactivity studies in which information on the exact silymarin composition plays a crucial role. Graphical Abstract.

Plant growth and yield are affected often by stress conditions including drought, which is the most important abiotic stress to reduce crop production worldwide. Milk thistle is one of the momentous medicinal crops with high potential as a multiple-purpose plant for low-efficient cultivation systems in the arid and semiarid areas. In this experiment, the effect of Chitosan (100 and 200 mg/l) and salicylic acid (0.5 and 1 mM) was investigated on plant traits (morphological, physiological, and phytochemical) under different levels of water deficit (Field capacity (F.C), 70% F.C, 40% F.C). Data were recorded in a time course (3, 7, 14, and 21 days after stress) and subjected to statistical analyses. According to the results, morphological, physiological, and phytochemical traits of the plant were significantly affected by water deficit, elicitors, and stress durations. Comparing the stress levels showed that severe water stress (40% F.C) significantly reduced growth and yield, while mild stress (70% F.C) did not show significant difference to non-stress treatment (F.C). The results showed that both chitosan and salicylic acid elicitors increased growth and yield, stress tolerance of plants under water-deficit conditions, and promotion of flavonoids, but chitosan has a more prominent effect. Under severe stress conditions, chitosan increased the yield of fresh and dry weight by 76.4% and 72.4%, but salicylic acid increased fresh weight and dry weight by 27.1% and 58.8%, respectively. Conversely, salicylic acid resulted in a 77.8% increase in grain yield, while that of chitosan was 75.0%. On the other hand, the content of silybin A in treatments of salicylic acid and chitosan, was increased by 2.9 and 9.2 mg/g, respectively, while the content of silybin B was increased by 6.48 and 9.48 mg/g, respectively. The role of the elicitors in reducing the negative effects of water stress and plant tolerance is due to stimulation of osmoregulation through proline and soluble sugar accumulation, reduction of malondialdehyde level, and production of antioxidant enzymes.

Cadmium is an important widely distributed heavy metal in the environment due to its several industrial uses, while milk thistle is an important herb and is a source of several antioxidant particularly silymarin which is a pharmacological active substance present in seeds of milk thistle plant (Silybum marianum). The current study investigated pathological effects of cadmium (Cd) and their amelioration with silymarin (SL) and milk thistle (MT) quails. A total of 144 quails were equally divided into 9 groups and given different combinations of cadmium chloride (150 and 300 mg/kg feed), SL (250 mg/kg), and MT (10 g/kg) feed. Parameters studied were clinical signs, mortality, organ weights, testes weight and volume, and gross and microscopic pathology. Results of this study indicated an increased mortality and reduced body weight in cadmium-treated quails. Quails were dull, depressed compared with control. Swollen hemorrhagic liver along with atrophied testes were also observed in these groups. No active spermatozoa were observed in lumen of seminiferous tubules of Cd-treated birds presenting arrest of spermatogenesis. Supplementing MT and SL ameliorated mortality, organ weights, spermatogenesis, and histopathological lesions. It may be concluded that MT and SL proved beneficial in cadmium-induced toxicities in Japanese quails.

The present research attempted to investigate the role of sodium nitroprusside (SNP) as a NO donor in yield and accumulation of active substances in milk thistle under drought stress in a 2-year farm experiment. In this experiment, two genotypes of milk thistle (Hungarin and Sari) were sprayed with SNP solutions (0, 100, and 200 µM) under water stress (control or withholding of irrigation from the stages of stem elongation and anthesis). Withholding of irrigation decreased the grain and silymarin yield and increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) content. Application of 100 µM SNP decreased the content of MDA and H2O2 in plants submitted to water deficit and as a result, prevented silymarin yield reduction under stress by increasing grain yield. In both years, with increasing the intensity of stress, taxifolin content, silychristin, silybin A and B, as well as isosilybin B were increased in both genotypes. While, exogenous NO further enhanced taxifolin, silychristin, silybin B, and isosilybin B accumulation, compared with plants solely grown under water deficit without SNP. The results of this study indicated that SNP application, especially at the dose of 100 µM, prevented the leaf water loss and reduces irrigation times from eight times to six or four times under drought stress from the stages of anthesis and stem elongation, respectively, and thus improved grain yield in milk thistle. Moreover, exogenous application of SNP to increasing taxifolin synthesis further enhanced secondary metabolites’ performance under conditions with low water availability.

The present study examined the chemical compositions as well as the antioxidant and antimicrobial activities of the vegetal oils of milk thistle (Silybum marianum) (MTO) and mastic (Pistacia lentiscus) (MO). The mastic oil extract was shown to have higher total phenolic and flavonoid contents than the oil extract of the milk thistle. The fatty acid and sterol compositions of the oil extracts were determined using gas chromatography coupled to flame ionization detection (GC-FID). The main fatty acids identified were palmitic, oleic, and linoleic acids. The main sterols found in milk thistle oil were β-sitosterol and campesterol, followed by Δ-7-stigmastenol, stigmasterol, Δ-7-avenasterol, and Δ-5-avenasterol. The most abundant sterol in mastic oil was β-sitosterol, followed by campesterol, Δ-5-avenasterol, and stigmasterol. The volatile compounds of the two vegetal oils were evaluated by headspace solid-phase microextraction (HS-SPME). In both oils, monoterpenes and non-terpenes were found to be the dominant volatile compounds in the mastic and milk thistle vegetal oils. 1,8-Cineole, methylpyrazine, 2,5-dimethylpyrazine, and hexanal were found to be the major volatile compounds of milk thistle oil, whereas myrcene and α-pinene were the major volatile compounds found in mastic oil. The antioxidant activities of the oil extracts were evaluated using various methods, such as DPPH, the ferric reducing power, the iron-chelating effect, and the β-carotene bleaching assay. In all methods, mastic oil exhibited a higher activity than milk thistle oil. Furthermore, both oils exhibited antibacterial activity, but mastic oil was the most potent, particularly against Gram-negative bacteria. Given their high total phenolic and flavonoid contents, the presence of volatile bioactive compounds, and their sterol and fatty acid compositions, the two oil extracts possess high potential for pharmaceutical and cosmetic applications and for utilization as natural preservative ingredients in food.

Background Delayed gastric emptying play an important role in the pathology of functional dyspepsia. Owing to their functional attributes in alleviating the gastrointestinal disorders, single or polyherbal formulations have gained attention to treat the symptoms of functional dyspepsia. We have investigated the safety and efficacy of a novel formulation of Ferula asafoetida oleo resin and standardized Silybum marianum extract (Asdamarin). Methods The effect of asdamarin on delayed gastric emptying was investigated in Sprague Dawley rats using phenol red method. The acute and sub-acute oral toxicity was evaluated in wistar rats following OECD guidelines 425 and 407 respectively. The data were analyzed by one-way ANOVA using GraphPad Prism 5.0 software. Results Oral administration of Asdamarin dose-dependently improved the delay in gastric emptying as evident from the significant increase in the gastrointestinal transit time (p

The present study investigates the hepatoprotective effect of a novel zinc-containing drug acyzol in comparison with silymarin, a medicinal extract of milk thistle (Silybum marianum). The hepatoprotective effect was studied in 40 albino nonlinear male rats in a model of toxic liver injury induced by intragastric administration of carbon tetrachloride. Both drugs were diluted in water and administered intragastrically at doses 10 mg/kg (acyzol) and 100 mg/kg (silymarin) for 10 days twice daily, after development of clinical toxic hepatitis. Biochemical and functional indicators of the liver parenchyma demonstrated that both drugs reduced mortality, normalized the body and relative liver weight, reduced intensity of cytolytic, cholestatic, and mesenchymal inflammatory syndromes, and restored liver function. The study demonstrates that acyzol and silymarin have comparable hepatoprotective effect, thus, providing a rationale for the use of acyzol in complex therapy of toxic hepatitis and hepatosis.

Gentamicin is an aminoglycoside with nephrotoxic effects; however, it seems that antioxidants such as vitamin E, milk thistle, and chicory extracts can reduce these effects. To test this, 60 male Wistar rats (200–250 g) were randomly allocated into six groups (n = 10). Each animal received intraperitoneal injections daily for 14 days: group 1—distilled water (1 ml) (control); group 2—gentamicin; group 3—gentamicin and milk thistle; group 4—gentamicin and chicory; group 5—gentamicin and vitamin E; and group 6—gentamicin, vitamin E, milk thistle, and chicory. At termination, blood was taken, to measure the serum levels of blood urea nitrogen (BUN) and creatinine, and the kidneys were taken, sampled, and processed for examination using a transmission electron microscope. Using milk thistle, chicory and vitamin E all showed a decrease in both dense bodies and damage to the nucleus. These observations were more pronounced in the group that received milk thistle, chicory, and vitamin E together. The levels of BUN and creatinine in all treatment groups were significantly lower compared to those of the gentamicin group (group 2). In conclusion, milk thistle, chicory, and vitamin E, individually, can reduce kidney damage caused by gentamicin, but they have a greater effect in reducing damage if used together.

The liver is the largest, important organ and the site for essential biochemical reactions in the human body. It has the function to detoxify toxic substances and synthesize useful biomolecules. Therefore, damage to the liver leads to grave consequences. This damage resulted from chronic alcoholic abuse, viral hepatitis or inherited metabolic disease. Liver damage is associated with cellular necrosis, fibrosis, and increase in tissue lipid peroxidation and depletion in tissue glutathione level. Most of the hepatotoxic chemicals damage liver cells mainly by inducing lipid peroxidation and other oxidative damages in the liver. Natural antioxidants are found in many compounds classified as secondary plant metabolites, e.g. polyphenols (phenolic acids and flavonoids) and terpenoids (carotenoids), and the consumption of foods that contain these compounds in large quantities seems to play an important role in prophylaxis against many diseases. Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical disease. More attention has been paid to the protective effects of natural antioxidants against drug induced toxicities especially whenever free radical generation is involved. Popularity of herbal remedies is increasing and at least one quarter of patients with liver disease use botanicals. The World Health Organization (WHO) estimates that 80 percent of the population of some Asian and African countries presently use herbal medicine for some aspect of primary health care. Some medicinal herbs have proven hepatoprotective potential. Silybum marianum (milk thistle) has been used to treat liver diseases since the 16th century. Its major constituents are the flavonoids silibinin, silydianin, silychristin, and isosilibinin, of which silibinin is the biologically most active compound and used for standardization of pharmaceutical products.

Background Several anti-arthritic drugs and synthetic antioxidants have wide pharmaceutical uses and are often associated with various side effects on the human health. Dietary seed oils and their minor components like policosanol may offer an effective alternative treatment for arthritic and oxidative-stress related diseases. The biological effects of seed oils were affected by different parameters such as the stage of seed maturity. Hence, this study seeks to determine the policosanol content, antioxidant and anti-arthritic activities of milk thistle (Silybium marianum L.) oil extracted at various stages of seed maturation. Methods Milk thistle oil samples were extracted from seeds collected at three maturation stages (immature, intermediate, and mature). The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays were used to determine the antioxidant activity of the extracted oils. The anti-arthritic activity of oil samples was evaluated with bovine serum protein denaturation and egg albumin denaturation methods. Gas chromatography coupled to mass spectrometry (GC-MS) was employed to determine the policosanol profile. Results Policosanol profile, antioxidant and anti-arthritic activities of milk thistle oil were influenced by the seed maturity stages. The oil extracted from the immature seeds had the highest total policosanol content (987.68 mg/kg of oil) and displayed the maximum antiradical activity (96.42% and 90.35% for DPPH test and ABTS assay, respectively). Nine aliphatic alcohols were identified in the milk thistle oil. The dominant poliosanol in the mature seed oil was octacosanol (75.44%), while triacontanol was the major compound (40.25%) in the immature seed oil. Additionally, the maximum inhibition of bovine serum protein denaturation (92.53%) and egg albumin denaturation (86.36%) were observed in immature seed oil as compared to mature seed oil. A high correlation was found between the total policosanol content, anti-arthritic activity and antioxidant capacity of oil. Conclusions The milk thistle oil exhibited a potential anti-arthritic and antioxidant activities and that it might contribute to the protection of humans from a variety of diseases like rheumatoid arthritis. Also, it could serve as natural antioxidant and anti-arthritic agents for application in the food industries and pharmaceutic. Policosanol level in the seed oils might contribute to their anti-arthritic and antioxidant activities.

Silybum marianum L. is a medicinal plant used in the treatment for jaundice and liver diseases. In this study, an adventitious root culture was developed for the production of health promoting phytochemicals. Adventitious roots were induced from nodal explants on solid Murashige and Skoog medium supplemented with 1.0 mg l−1 of α-Naphthalene acetic acid. Growth kinetics of the roots was investigated every week, for 8 weeks of culture period. Highest fresh biomass formation (153 mg l−1) was observed in 6-week old cultures. Adventitious roots were harvested from different growth stages as control (CTR), lag phase (LAG), logarithmic phase (LOG) or stationary phase (STN). Metabolite profiling of the samples was investigated using electro spray ionization time of flight mass spectrometry. Significant phenylpropanoids such as cinnamic acid and di-hydro kaempferol were predominantly found in LOG phase, whereas the highest amount of malonic acid was detected in STN as compared to other growth phases. More sucrose content was detected in CTR, while the tryptophan content was higher in LOG phase. Among the vital fatty acids, prostaglandin A1 and phenyl acetic acid were at highest levels in STN phase. However, more brassicasterols were observed in LAG phase than other growth phases. Punicic acid and lignan pinoresinol were detected abundantly in the LOG phase. Biochemical characterization revealed significant correlations between silymarin content and DPPH as well as TPC and TFC in the growth curve. Interestingly, among all growth stages there was no correlation of PAL activity with TFC and silymarin content.

Seeds of milk thistle, Silybum marianum (L.) Gaertn., are used for treatment and prevention of liver disorders and were identified as a high priority ingredient requiring a validated analytical method. An AOAC International expert panel reviewed existing methods and made recommendations concerning method optimization prior to validation. A series of extraction and separation studies were undertaken on the selected method for determining flavonolignans from milk thistle seeds and finished products to address the review panel recommendations. Once optimized, a single-laboratory validation study was conducted. The method was assessed for repeatability, accuracy, selectivity, LOD, LOQ, analyte stability, and linearity. Flavonolignan content ranged from 1.40 to 52.86 % in raw materials and dry finished products and ranged from 36.16 to 1570.7 μg/mL in liquid tinctures. Repeatability for the individual flavonolignans in raw materials and finished products ranged from 1.03 to 9.88 % RSDr, with HorRat values between 0.21 and 1.55. Calibration curves for all flavonolignan concentrations had correlation coefficients of >99.8 %. The LODs for the flavonolignans ranged from 0.20 to 0.48 μg/mL at 288 nm. Based on the results of this single-laboratory validation, this method is suitable for the quantitation of the six major flavonolignans in milk thistle raw materials and finished products, as well as multicomponent products containing dandelion, schizandra berry, and artichoke extracts. It is recommended that this method be adopted as First Action Official Method status by AOAC International.

Limited treatment options in infectious diseases caused by resistant microorganisms created the need to search new approaches. Several herbal extracts are studied for their enormous therapeutic potential. Silymarin extract, from Silybum marianum (milk thistle), is an old and a new remedy for this goal. The purpose of this study is to evaluate the antibacterial and antiadherent effects of silymarin besides biofilm viability activity on standard bacterial strains. Minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), antiadherent/antibiofilm activity, and effects on biofilm viability of silymarin were evaluated against standard bacterial strains. MIC values were observed between 60 and >241 μg/mL (0.25->1 mmol/L). Gram-positive bacteria were inhibited at concentrations between 60 and 120 μg/mL. Gram-negative bacteria were not inhibited by the silymarin concentrations included in this study. MBC values for Gram-positive bacteria were greater than 241 μg/mL. Adherence/biofilm formations were decreased to 15 μg/mL silymarin concentration when compared with silymarin-untreated group. Silymarin reduced the biofilm viabilities to 13 and 46 % at 1 and 0.5 mmol/L concentrations, respectively. We demonstrated that silymarin shows antibacterial and antiadherent/antibiofilm activity against certain standard bacterial strains which may be beneficial when used as a dietary supplement or a drug.

According to the results obtained in this study, drought stress can enhance the accumulation of silymarin in milk thistle seeds. Moreover, under drought stress, the share of silybin increased which possess the greatest degree of biological activity among the silymarin components. Silymarin, an isomeric mixture of flavonolignans found in milk thistle (Silybum marianum (L.) Gaertn) seeds, has been used for its hepatoprotective effects for more than 2,000 years. Biosynthesis and accumulation of active substances like silymarin in plant tissues highly interacts with the environmental conditions. Effects of moderate and severe drought stress (based on soil moisture depletion) on silymarin content and composition in milk thistle seeds were evaluated in a field study. Averaged across treatments, milk thistle seeds contained 19.3 g kg−1 silymarin. Drought stress enhanced silymarin accumulation in milk thistle seeds. Plants grown under moderate and severe drought stress treatments contained 4 and 17 % greater silymarin than those grown in well-watered condition, respectively. Greater content of sylimarin in stressed plants was attributed to more contents of silybin, isosilybin and silychristin, while silydianin content was lower under drought condition. According to the results obtained in this study, drought stress enhanced accumulation of silymarin in milk thistle seeds and improved its quality by increasing the share of silybin, which possess the greatest degree of biological activity among the silymarin components.

Silybum marianum, commonly known as Milk thistle, is a popular herbal supplement used for the treatment of jaundice and liver cirrhosis worldwide. Here we established methods for somatic embryogenesis and comparative metabolite profiling of the different growth phases during embryogenesis in S. marianum. Highest embryogenic potential was observed for calli previously derived from petiole explants on Schenk and Hildebrandt medium containing 2.5 mg l−1 2,4-dichlorophenoxyacetic acid (2,4-D) and 1.5 mg l−1 N6-benzyladenine (BA). Somatic embryos (SE) were induced when embryogenic calli with pre-embryoid masses (PEMs) were subcultured on same media as used for induction of embryogenic callus. Highest number of somatic embryos (46 somatic embryo per callus) was observed at 1.5 mg l−1 2,4-D and 1.5 mg l−1 BA, however ½ strength MS medium showed optimal response for maturation followed by germination of somatic embryos at 1.5 mg l−1 GA3. Metabolite profiles from developmental stages of non-embryogenic callus (NEC), PEMs, SE and embryos germinating into intact plantlets (GSE) were obtained using Electro spray ionization mass spectrometry ESI/MS. Principal component analysis (PCA) was carried out to identify key metabolites in different growth phases during somatic embryogenesis. The loading scatter plots enabled the detection of several bin masses responsible for separating samples from different growth stages. Based on the values of % total ions count and average intensity of selected bins in all biological samples, putatively known metabolites were obtained from in-house bin program. Amino acids associated with various biosynthetic pathways like arginine, asparagine and serine were abundantly detected in GSE, while they were detected at decreased intensities in NEC. However, tryptophan was measured with increased signals in SE when compared to other growth phases. Glucose, fructose and fructose-6-phosphate were mostly accumulated in NEC; however they were detected with lowest intensities in GSE. Moreover, sucrose and significant secondary metabolites like cinnamic acid, kaempferol, quercetin, myricetin, linolenic acid, and 5-enolpyruvyl-shikimate-3-phosphate were found at higher amount in SE when compared to other embryogenic phases.

Silybum marianum is an important medicinal plant of the family Asteraceae, well known for its set of bioactive isomeric mixture of secondary metabolites "silymarin", primarily acting as a hepato-protective agent. Abiotic stress augments plant secondary metabolism in different plant tissues to withstand harsh environmental fluctuations. In the current study, our aim was to induce drought stress in vitro on S. marianum under the influence of different photoperiod treatments to study the effects, with respect to variations in secondary metabolic profile and plant growth and development. S. marianum was extremely vulnerable to different levels of mannitol-induced drought stress. Water deficiency inhibited root induction completely and retarded plant growth was observed; however, phytochemical analysis revealed enhanced accumulation of total phenolic content (TPC), total flavonoid content (TFC), and total protein content along with several antioxidative enzymes. Secondary metabolic content was positively regulated with increasing degree of drought stress. A dependent correlation of seed germination frequency at mild drought stress and antioxidative activities was established with 2 weeks dark + 2 weeks 16/8 h photoperiod treatment, respectively, whereas a positive correlation existed for TPC and TFC when 4 weeks 16/8 h photoperiod treatment was applied. The effects of drought stress are discussed in relation to phenology, seed germination frequency, biomass build up, antioxidative potential, and secondary metabolites accumulation.

Artichoke, borututu and milk thistle are three medicinal plants widely consumed as infusions or included in dietary supplements (e.g., pills and syrups). Despite their high consumption, studies on nutritional value and primary metabolites are scarce, being only reported the composition in secondary metabolites such as phenolic compounds. Therefore, their nutritional value was assessed and analytical tools (liquid and gas chromatography coupled to different detectors) were used to distinguish the chemical profiles namely in hydrophilic (sugars and organic acids) and lipophilic (fatty acids and tocopherols) compounds. Chromatographic techniques are important analytical tools used in the identification and quantification of several molecules, also being a standard requirement to distinguish different profiles. Borututu gave the highest energetic value with the highest content of carbohydrates and fat, sucrose and total sugars, shikimic and citric acids, α-, β-, δ- and total tocopherols. Artichoke had the highest ash and protein contents, oxalic acid, SFA (mainly palmitic acid acid), and γ-tocopherol, as also the best n6/n3 ratio. Milk thistle showed the highest levels of fructose and glucose, quinic acid and total organic acids, PUFA, mainly linoleic acid, and the best PUFA/SFA ratio. The hydrophilic compounds identified in the studied plants, mostly sugars, are the responsible for the energetic contribution of their widely consumed infusions. Otherwise, the bioactivity of lipophilic compounds namely, unsaturated fatty acids and tocopherols, is lost in those preparations but can be recovered in dietary supplements based on the plants. As far as we know this is the first report on detailed composition of molecules with nutritional features. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support to the research centre CIMO (PEst-OE/AGR/UI0690/2011).

The industrial solid wastes generated during the production of silymarin from the fruits of milk thistle Silybum marianum was used as the substrate. Preparation and evaluation of the feeds produced by solid-state fermentation (SSF) of the industrial solid wastes was carried out. The protein content of the fermented feed (FF) from a combination of Aspergillus niger and Candida tropicalis was the highest among the examined strains. The optimal process parameters for protein enrichment with SSF using A. niger and C. tropicalis included incubation temperature of 30.8 °C, fermentation time of 87.0 h, and initial moisture content of 59.7 %. Under these conditions, the value additions of FF occurred. The fiber of FF was decreased by 25.07 %, while the digestibility of protein, protein content, and the ratio of total essential amino acids to total amino acids were increased by 79.85, 16.22, and 8.21 %, respectively. The analysis indicated that FF contained 1.44 mg/kg flavonoids and 0.5 mg/kg silybin, which significantly increased by 2.42 and 1.63 times, respectively than those in unfermented substrates. FF recorded reduced molecular weight of proteins from 20.1 to 44.3 kDa to below 14.3 kDa. The results of feeding trial of FF replacement with soybean meal in broilers diets for 8 weeks showed that FF significantly improved carcass characteristics including abdominal fat rate, serum biochemical parameters including aspartate transaminase, blood urea nitrogen and high density lipoprotein cholesterol, and immune responses of broilers. A potential feed quality improvement was achieved through mixed strains SSF of industrial solid wastes of S. marianum fruits.

A highly abundant β-glucosidase from petals of Silybum marianum has been purified and characterized for its physico-kinetic properties. The 135 kDa enzyme was a homodimer with subunit molecular mass of 67.6 kDa. The characteristic catalytic properties of the enzyme included acidic pH optimum (5.5), meso-thermostability, and β-linked substrate specificity with preference for gluco-conjugate but a marked (>50 %) activity with D-fuco-conjugates and considerable (~16 %) activity towards D-galacto-conjugates. The enzyme showed high affinity for p-nitrophenyl glucoside (pNPG) with Km and Vmax values of 0.25 mM and 5.35 μkat.mg−1 enzyme protein. Thus, the enzyme had a very high (292,000 M−1.s−1) catalytic efficiency (Kcat/Km). Thermal catalytic optimum of enzyme was 40 °C with activation energy value 8.26 kCal.Mol−1. The enzyme showed significant insensitivity to D-gluconic acid lactone inhibition (57 % at 5 mM) with an apparent Ki 3.8 mM. The transglucosylating ability of enzyme was noticed for glucosylation of geraniol and withaferin-A with pNPG as glucosyl donor but cellobiose did not serve as the glycosyl donor. Partial proteomics of the enzyme revealed two peptide fragment sequences, VTPSNEVH and KRSEESNF. These motifs showed significant matching/sequence conservation with some other glycohydrolases. The novelties of purified enzyme hold potential to expand a library of catalytically characteristic members of the hydrolase family from plants for use in biotransformation applications.

We investigated the effects of silymarin, a component of the extract from milk thistle (Silybum marianum) on the level of anxiety in rats and also the potential role of the serotonergic system in the modulatory influences of silymarin on anxiety-related behavior. The elevated plus-maze test was used for testing the above level. Oral administrations of silymarin (35, 70, 140, and 280 mg per rat) for 2 weeks induced an anxiolytic-like effect shown by specific increases in normalized values of the open arm time (OAT) and open arm entries (OAE) in the elevated plus-maze. Intraventricular infusion of a 5-HT1A receptor agonist, 8-OH-DPAT (5, 10, and 25 ng per rat), increased the OAT and OAE, indicating that this agent also possesses an anxiolytic effect. Similar injections of a 5-HT1A receptor antagonist, NAN190 (0.25, 0.5, and 1.0 μg per rat), intensified anxiety-related behavior. The least effective dose of intraventricularly injected 8-OH-DPAT (5 ng per rat), when co-administered with silymarin (35, 70, and 140 mg per rat, pretreatment for 2 weeks), decreased the anxiety-related behavior significantly. An effective dose of NAN190 (0.5 μg per rat) combined with silymarin in the above-mentioned dosage provided significant decreases in the OAT and OAE. These results demonstrate that the effects of silymarin on anxiety are mediated, at least partly, by 5-HT1A receptors of serotonin.

A high-performance liquid chromatographic/tandem mass spectrometric method was developed for the determination of the major bioactive flavonolignans in silymarin, a herbal remedy extracted from the milk thistle Silybum marianum. In this study, eight active components of silymarin with the same elemental composition, including silychristins A and B, silydianin, silybin A and B, isosilybin A and B and an unknown compound were completely separated. Furthermore, three additional components were detected and partly separated; presumably two silybin stereoisomers and one isosilybin stereoisomer. The collision-induced dissociation (CID) MS/MS spectra of these silymarin constituents were studied: the spectral similarity values of the component pairs were determined, and simple criteria were found for distinguishing the components.

As the uses of herbal medicines from traditional natural products are increased, the need for pharmacokinetic studies and relevant data are also increased for safe pharmacotherapy. The market entry for the traditional herbal medicine is easier compared with that for synthetic drugs because of a lower regulatory barrier. Thus, the exact mechanisms for the absorption, distribution, metabolism and excretion of active components in herbal medicines and the potential herb-drug interactions are not always fully understood. Recently, there has been an increasing interest in pharmacokinetic studies of herbal remedies and relevant data of commonly used herbal remedies are accumulating in this field. In this review, the effects of nine botanicals (ginkgo, green tea, grapes, licorice, saw palmetto, garlic milk thistle, ginseng and St. John's wort) on metabolic enzymes and transporters affecting absorption and disposition of herbal products are summarized. The source of samples (extracts and individual components), the species (human and animal) and in vivo and in vitro systems were separately reviewed for a better understanding of herb-drug interactions.

Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

Silymarin (Sm) from the fruit of Silybum marianum is an isomeric mixture of pharmacologically active flavonolignans which are formed by oxidative coupling of taxifolin (Tx) and coniferyl alcohol (CA). Suspension cultures of this plant constitutively secrete small amounts of Sm into the extracellular medium. Production can be increased by inclusion of cyclodextrins (CDs) in cultures. Both hydroxylated (RHCD) and dimethylated (RMCD) CDs strongly induced prompt accumulation of CA in the medium followed by a late production of flavonolignans. Simultaneous addition of methyl jasmonate (MJ) and RMCD to cells did not significantly modify CA release or flavonolignan accumulation. Delayed addition of MJ to cultures subcultivated in medium containing RMCD markedly influenced Sm production by promoting conversion of the previously formed CA precursor.

Cancer is the major health problem around the world. Research efforts in last few decades have been successful in providing better and effective treatments against both early stage and localized cancer but clinical options against advanced metastatic stage/s of cancer remain limited. The high morbidity and mortality in most of the cancers are attributed to their metastatic spread to distant organs. Due to its extreme clinical relevance, the metastasis has been extensively studied and is now understood as a highly complex biological event that involves multiple steps including acquisition of invasiveness by cancer cells, intravasation into circulatory system, survival in the circulation, arrest in microvasculature, extravasation and growth at distant organs. The increasing understanding of molecular underpinnings of these events has provided excellent opportunity to target metastasis especially through non-toxic and biologically effective nutraceuticals. Silibinin, a popular dietary supplement isolated from milk thistle seed extracts, is one such natural agent that has shown biological efficacy through pleiotropic mechanisms against variety of cancers and is currently in clinical trials. Recent pre-clinical studies have also shown strong efficacy of silibinin to target cancer cell’s migratory and invasive characteristics as well as their ability to metastasize to distant organs. Detailed mechanistic analyses revealed that silibinin targets signaling molecules involved in the regulation of epithelial-to-mesenchymal transition (EMT), proteases activation, adhesion, motility, invasiveness as well as the supportive tumor-microenvironment components, thereby inhibiting metastasis. Overall, the long history of human use, remarkable non-toxicity and pre-clinical efficacy strongly favor clinical use of silibinin against advanced metastatic cancers.

The possible role of polyamines (PAs) in the regulation of silymarin (Sm) production in milk thistle [Silybum marianum (L.) Gaernt] cell suspension cultures was studied in a young cell culture line (H2 line) and in a synchronized cell line (>3 years; H1 line). The effect of two exogenous PAs, putrescine (Put) and spermidine (Spd), and a number of metabolic inhibitors (L-canavanine, DL-α-difluoromethylornithine, methylglyoxal-bis-guanylhydrazone, cyclohexylamine) on the production of Sm during the growth cycle were analyzed. The results suggest that PAs are not directly involved in the Sm synthesis pathway. In our cell culture system, Sm production and PA contents were determined by the age of the suspension culture cells: with increasing age, the suspension culture cells showed a decreasing capacity to reach the stationary phase during prolonged subculture that was associated with a decreased production of Sm, a steady increase in PA content, and a constant Put/Spd ratio. The synchronization of dividing cells from the S. marianum H1 line did not modify this behaviour. In young cell suspensions, maximum Sm production occurred in the stationary phase, concurrent with the cellular PA contents reaching their minimum value. At the start of the stationary phase, the high percentage of cells in the growth phases (G0/G1) and a transient increase in the Put/Spd ratio were accompanied by maximum Sm production and a blockade of cell division.

The morphogenic potential and free-radical scavenging activity of the medicinal plant, Silybum marianum L. (milk thistle) were investigated. Callus development and shoot organogenesis were induced from leaf explants of wild-grown plants incubated on media supplemented with different plant growth regulators (PGRs). The highest frequency of callus induction was observed on explants incubated on Murashige and Skoog (MS) medium supplemented with 5.0 mg l−1 6-benzyladenine (BA) after 20 days of culture. Subsequent transfer of callogenic explants onto MS medium supplemented with 2.0 mg l−1 gibberellic acid (GA3) and 1.0 mg l−1 α-naphthaleneacetic acid (NAA) resulted in 25.5 ± 2.0 shoots per culture flask after 30 days following culture. Moreover, when shoots were transferred to an elongation medium, the longest shoots were observed on MS medium supplemented with 0.5 mg l−1 BA and 1.0 mg l−1 NAA, and these shoots were rooted on a PGR-free MS basal medium. Assay of antioxidant activity of in vitro and in vivo grown tissues revealed that significantly higher antioxidant activity was observed in callus than all other regenerated tissues and wild-grown plants.

The biosynthesis of silymarin, a potent antihepatotoxic compound, from the dried fruits of Silybum marianum L. Gaertn in hairy root cultures can be stimulated by a yeast extract elicitor. These results correlated with culture time, and the biosynthesis reached a maximum of 0.47 mg g−1 DW by 72 h after culture (2-fold higher than the control). Lipoxygenase activity and linoleic acid content were stimulated by this treatment, suggesting that the jasmonate pathway may mediate the elicitor-induced accumulation of silymarin. The H2O2 content increased 24 h after elicitation and did not have marked changes between 48 and 72 h. In addition, the tocopherol content (especially α- and δ-tocopherols) increased 72 h after elicitation in comparison with non-treated cultures. Ascorbate had trace changes during feeding time and was lower than the control. The antioxidant activity was assayed by the 1-1-diphenyl-2-picrylhydrazyl stable free radical method and results were calculated base on an IC50 that increased upon treatment, especially 24 h after treatment, with changes related to H2O2 content. These observations suggested that reactive oxygen species may mediate elicitor signals to the jasmonate pathway that lead to the production of silymarin.

Production of silymarin and the effect of the elicitor, methyl jasmonate (MeJA), was monitored in cell cultures of Silybum marianum over 4 years. Silymarin concentrations gradually declined after prolonged subculture, making the success of elicitor strategy limited in long-term cultures. The continuous presence of MeJA in cultures for an extended period was necessary for induction of silymarin accumulation. A repeated elicitor strategy was not a good option for improving silymarin productivity in batch cultures. Removal of medium from elicited cultures and addition of fresh medium avoided the toxic effects of elicitor accumulation, allowing the system to respond to a repeated MeJA treatment without loss of productivity.

Interactions of silybin and dihydroquercetin (taxifolin), flavanonols from milk thistle [Silybum marianum (L.) Gaertn.] fruits, with Langmuir monolayers of lecithin and bilayers of liposomes are compared. It is established that the investigated flavanonols have different mechanisms of action. Taxifolin produces predominantly membrane-stabilizing action whereas silybin is characterized by immobilization in the hydrophobic part of the phospholipid bilayer with the formation of more hydrophilic micellar structures. The presence of silybin and taxifolin in the liquid extract of milk thistle fruits suggests that a dual mechanism of action may occur in this preparation and also in other combined medicines based on these fruits. The results of this study show good prospects for creating combined preparations based on milk thistle fruit, taxifolin, and other flavonoids (quercetin, rutin, diosmin, etc.) possessing pronounced membrane-stabilizing action.

The fruits of Silybum marianum L. (milk thistle) has been used for the treatment of hepatic and biliary diseases since ancient times. As separation techniques improved several isomers of silybin—the first determined active compound of milk thistle—have been described. Moreover, a new variety, the white-flowered S. marianum was discovered which contains deoxy-derivatives of some of the flavanolignans found in the purple-flowered variety. Based on this observation Nyiredy presumed that the deoxy-derivatives of all known flavanolignans of the purple-flowered variety are present in the white-flowered one. To prove this prediction several separations have been developed by the use of “PRISMA” principle.

Silibinin is a flavonolignan extracted from milk thistle with cancer chemopreventive activity in preclinical models of prostate and colorectal cancer. A milk thistle extract, of which silibin is a major component, has recently been shown to exacerbate mammary carcinogenesis in two rodent models. We tested the hypothesis that consumption of silibinin or silipide, a silibinin formulation with pharmaceutical properties superior to the unformulated agent, affect breast cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma mouse model. Mice received silibinin or silipide (0.2% silibinin equivalents) with their diet from weaning, and tumour development was monitored by weekly palpation and the number and weight of neoplasms at the end of the experiment. Intervention neither promoted, nor interfered with, tumour development. The result suggests that promotion of carcinogenesis is not a feature of silibinin consistent across rodent models of mammary carcinogenesis.

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.

Background Silymarin derived from the milk thistle plant “Silybum marianum” is composed of four major flavonolignans. Clinical as well as experimental studies indicate hepatoprotective effects of silymarin. However, the underlying mechanisms are only incompletely understood. The aim of this study was to assess the effect of oral administration of a defined silymarin extract in the model of acute carbon tetrachloride (CCl4) induced liver injury. Methods A single dose of a silymarin extract (SE; 20 or 100 mg/kg body weight) was given to rats by oral gavage. Subsequently, rats were injected with a single dose of CCl4 (2 ml/kg body weight). Results After 24h, analysis of liver to body weight ratio, serum levels of transaminases and histological analysis revealed a marked liver damage which was inhibited by SE in a dose dependent manner. CCl4-induced expressions of pro-inflammatory and pro-fibrogenic genes were significantly reduced in SE treated rats. Molecular analysis revealed that SE reduced the expression of the pro-inflammatory chemokine MCP-1, the pro-fibrogenic cytokine TGF-beta as well as collagen I in isolated human hepatic stellate cells (HSC), which are the key effector cells of hepatic fibrosis. Conclusion Oral administration of the tested silymarin extract inhibited hepatocellular damage in a model of acute liver injury. Moreover, we newly found that the silymarin extract had direct effects on pro-inflammatory and pro-fibrogenic gene expression in HSCs in vitro. This indicates that direct effects on HSC also contribute to the in vivo hepatoprotective effects of silymarin, and further promote its potential as anti-fibrogenic agent also in chronic liver disease.

Yellow starthistle, Centaurea solstitialis (Asteraceae), is an important invasive alien weed in the western United States. Currently established biological control agents attack only the capitula (flowerheads), and are not effectively controlling the plant in much of its range. The geographic center of diversity for the plant appears to be in Turkey, but no agents have been introduced from this country. Ceratapion basicorne (Coleoptera: Apionidae) is common in Central Turkey, attacking 25-100% of yellow starthistle plants. In a field experiment, Ceratapion spp. attacked 90% of yellow starthistle plants and 88% of milk thistle plants (Silybum marianum) but not seven other plant species, including artichoke and safflower. We suspect that a different species of insect attacked milk thistle, but they emerged before the plants were sampled. Laboratory tests showed that C. basicorne does not oviposit in milk thistle. Ceratapion basicorne appears to be more host specific than was suggested by previous studies of a population in Italy (Clement et al. 1989. Ann. Entomol. Soc. Am. 82: 741-747). The insect is gregarious, and the number of larvae per plant was positively correlated to root diameter. The level of damage to individual plants was positively correlated to the proportion of plants attacked, indicating aggregation both among plants and within plants. Field data did not show any impact of the insect on plant size or number of capitula, but germination rate of seeds produced by infested plants was 15% lower than for uninfested plants at two of three sites studied. © Springer 2005. This study was financially supported by Biotechnology and Biological Control Agency, Rome, Italy and the USDA-ARS European Biological Control Laboratory, Montferrier sur Lez, France. Identifications of weevils were made with the assistance of B.A. Korotyaev, Zoological Institute, St. Petersburg, Russia.

The problem of herb-drug interactions is being increasingly recognised. However, except for hypericum (Hypericum perforatum L.; St John’s wort), data on drug interactions with other herbs are still inconclusive, although research has started to fill in the gaps, and knowledge is being gained about this important safety issue. This review summarises clinical data on interactions between drugs and herbal medicines, which were compiled using the following databases: MEDLINE via PubMed, Web of Science® (from their inception until March 2005) and the Cochrane Library (until 2005, issue 1). Clinical data on herb-drug interactions, observed in case reports, case series or clinical trials, were included. Results are described for the following herbs: Devil’s claw (Harpagophytum procumbens D.C.), echinacea, evening primrose (Oenothera biennis L.), garlic (Allium sativum L.), ginkgo (Ginkgo biloba L.), goldenseal (Hydrastis canadensis L.), hawthorn, kava (Piper methysticum Forst.), milk thistle (Silybum marianum [L.] Gaertn.), peppermint, saw palmetto (Serenoa repens [Bartel] Small) and valerian. Information on herb-drug interactions is discussed through use of in vivo and experimental data, and conclusions are drawn when possible.

Objectives Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of Citrus aurantium, Echinacea purpurea, milk thistle (Silybum marianum), or saw palmetto (Serenoa repens) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods Twelve healthy volunteers (6 women, 6 men) were randomly assigned to receive C aurantium, E purpurea, milk thistle, or saw palmetto for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported “active” phytochemicals was determined for each supplement. Results Comparisons of presupplementation and postsupplementation phenotypic ratios suggested that these particular supplements had no significant effect on CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Phytochemical profiles indicated that C aurantium was devoid of the CYP3A4 inhibitor 6′,7′-dihydroxybergamottin. Quantities of fatty acids, flavonolignans, and cichoric acid were consistent with label claims for saw palmetto, milk thistle, and E purpurea, respectively. Conclusions Botanical supplements containing C aurantium, milk thistle, or saw palmetto extracts appear to pose a minimal risk for CYP-mediated herb-drug interactions in humans. Although the effects of E purpurea on CYP activity were minor, further study into the interaction potential of this botanical is merited. Clinical Pharmacology & Therapeutics (2004) 76, 428–440; doi: 10.1016/j.clpt.2004.07.007

Incubation of rat liver microsomes with preparations of grape flavonoids, dihydroquercetin, and silibinin increased their resistance to lipid peroxidation induced by NADPH-Fe2++. This was manifested in less pronounced accumulation of lipid peroxidation products and changes in activity of microsomal enzymes induced by lipid peroxidation. In vitro antioxidant activity of grape flavonoids markedly surpassed that of dihydroquercetin and silibinin. Addition of flavonoids into fodder led to moderate, statistically significant, and similar increase in the resistance of rat liver microsomes to ex vivo induced lipid peroxidation.

Silybin has a potent antibacterial activity, more potent than silymarin II, against gram-positive bacteria without hemolytic activity, whereas it has no antimicrobial activity against gram-negative bacteria or fungi. The mode of action of silybin against the gram-positive bacterial cell was examined by investigating the change in plasma membrane dynamics of bacterial cells using 1,6-diphenyl-1,3,5-hextriene (DPH) as a membrane probe and by assessing the inhibition of macromolecular synthesis using radiolabeled incorporation assay. The results showed that silybin inhibited RNA and protein synthesis on gram-positive bacteria.

Seeds from milk thistle (Silybum marianum Gaert L.) contain flavanolignan and dihydroflavanol compounds that have interesting and important therapeutic activities. The recovery of these silymarin compounds generally involves a two-step defatting and extraction process using organic solvents. This study examined the batch, single-stage extraction of whole and defatted seeds using ethanol, methanol, acetonitrile, and acetone as the solvents. In extracting defatted milk thistle seeds with organic solvents, extraction with ethanol resulted in the highest silymarin yield, although some potential degradation was observed. The maximum yields of taxifolin, silychristin, silydianin, silybinin A, and silybinin B in ethanol were 0.6, 4.0, 0.4, 4.0, and 7.0 mg/g of defatted seed, respectively. However, if silybinin A were the diastereoisomer of choice, methanol would be the preferred extraction solvent because it yielded the highest silybinin A to silybinin B ratio. Interestingly, lipid removal is an important extraction step, because defatted material yields twice the silymarin concentration.

Herbal products are being increasingly used as dietary supplements and therapeutic agents. However, much more research must be performed in order to determine the biological basis for their putative clinical effects. We tested the effects of milk thistle (Silybum marianum) extract on the differentiation and survival of cultured neural cells. Milk thistle enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their survival in culture. Milk thistle extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. Our data demonstrate that milk thistle extract can promote neuronal differentiation and survival, suggesting potential benefits of chemicals in this plant on the nervous system.

Lipids from the air-dried aerial part (AP) and seeds of Silybum marianum (L.) Gaerth. (Asteraceae) were studied. The class and fatty acid compositions of neutral lipids (AP, seeds) and glyco- and phospholipids (AP) were determined. Neutral lipids (NL) with a complicated set of lipophilic components, mainly triterpenols, sterols, and their esters predominated in the AP. The fatty acids of the AP were dominated by 16:0, 18:2 (glycolipids), and 18:3 (neutral lipids, phospholipids); of seed NL, by 18:2 and 18:1. The content and composition of flavolignans isolated from defatted seeds and the content of total protein in the meal were found.

Background: The deposition of amyloid peptides is associated with Alzheimer’s disease (AD). These amyloid peptides are derived from the amyloid protein precursor (APP). Silymarin, a standardized extract of milk thistle, which is currently used in liver diseases, may be effective in the inhibition of amyloid formation. However, its effect has not been assessed on APP expression. Results: In this study, first, the effect of silymarin was examined on the passive avoidance learning in a rat model of AD. This model was induced by the intracerebroventricular injection of Aβ peptide (Aβ1–42) in Wistar rats. Rats were treated with 70 and 140 mg/kgof the extract, once a day, for 4 weeks. Memory function that was evaluated in a shuttle-cage test, showed improvement upon administration of this extract. Brain amyloid plaques had also decreased upon administration of the extract. Furthermore, APP gene expression was compared in treated and untreated groups. The result showed that silymarin was able to suppress APP expression. Conclusion: Our results are in accordance with the in vitro tests concerning the positive antiamyloidogenic property of the main component of silymarin, namely silibinin. We suggest that the beneficial effect of sylimarin in the AD model is related to its capacity to disaggregate amyloid plaques and to suppress APP expression. Considering the limited side effects of silymarin, this compound could be of use in AD therapy.

The bioavailability of iron from local plants (black cumin seeds, milk thistle seeds, sesame seeds and thyme leaves) was investigated. Apparent absorption of iron was calculated by subtracting fecal iron (using total collection of feces) from iron intake in Sprague-Dawley rats. Two trials of animal feeding were performed. Liver and serum concentrations of iron, and serum hemoglobin concentration were taken as response parameters for the bioavailability. Dry thyme was particularly rich in iron (117.2 mg/100 g dry matter) and milk thistle seeds in crude fiber (25 g/100 g dry matter). Rats fed the dry thyme diet or that supplemented with 5% egg white died but when the diet was supplemented with 10% egg white, the animals survived. Iron intake and apparent and total iron absorption were highest for the rats fed the dry thyme-egg white diet. Liver weights for the groups fed black cumin seeds and dry thyme were significantly higher (p

Background and the purpose of the study: Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated. Methods: We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month). Results: A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin. Conclusion: This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy.