The emergence of multi-drug resistance in the class of ESKAPE pathogens such as Acinetobacter baumannii and Staphylococcus aureus has led to the search for anti-virulence mechanisms to overcome resistance posed by the existing antibiotics. Quorum sensing (QS), mediated by AbaI/AbaR circuits in A. baumannii and AgrA/AgrC circuits in S. aureus, regulates biofilm formation and virulence factor production in the two species, thereby serving as potential targets for phytocompound action. In the current study silybin, a flavonoid lignan from Silybum marianum, emerged as a potential QS modulator against both pathogens based on an integrated computational and experimental approach. Molecular docking studies predicted favourable interactions of silybin to the four regulatory proteins (-14.76 to -12.34 kcal/mol for AbaI and AbaR, -10.20 to -9.83 kcal/mol for AgrA and AgrC), binding functionally important amino acid residues in their active sites. Molecular dynamics simulations lasting 500 ns revealed that silybin binding decreased backbone and residue-level flexibility, increased compactness, reduced solvent-accessible surface area and restricted collective motion in comparison with their respective apo-proteins in all four targets. MM-GBSA calculations together with per-residue decomposition and contact analysis emphasized the role of van der Waals and electrostatic interactions contributed to the predicted binding energetics of the protein-ligand complexes. Silybin displayed in-vitro antibacterial activity, time-dependent inhibitory activity, and concentration-dependent antibiofilm activity up to 60% in A. baumannii and up to 70% in S. aureus. Downregulation was observed for genes involved in virulence in S. aureus, but not for abaI/abaR in A. baumannii. Overall, the findings support silybin as a potential QS- associated modulator with anti-biofilm activity against both pathogens. However, additional studies are required to establish QS-specific activity, selectivity, cytotoxicity, pharmacokinetic properties, and in-vivo efficacy.

Silymarin, a flavonolignan complex from Silybum marianum, and its principal constituent silybin have long been used as hepatoprotective and antifibrotic agents. In the liver, silymarin suppresses tissue inhibitor of metalloproteinases 1 (TIMP-1), a central regulator of matrix turnover in fibrogenesis. This effect is reproducible across several models of hepatic fibrosis, but its magnitude is inconsistent. Some studies report no or only a nonsignificant reduction in hepatic TIMP-1 with free silymarin, while others report a substantial decline. Much of this inconsistency tracks with formulation and route. The clinical use of silymarin is limited by low aqueous solubility, low bioavailability, and rapid clearance. Conjugating flavonolignans to β-cyclodextrin or phospholipids, or preparing a nanoparticle formulation, could address these limitations. Across the mRNA-based studies compiled here, complexed or nanoparticle-encapsulated preparations achieved significantly greater recovery of hepatic Timp1 toward baseline than free compound. Among nanocarrier formulations, gold nanoparticles are an attractive platform. Independent of any drug coating, they themselves exhibit hepatoprotective and antifibrotic activity in models of liver injury, although this intrinsic activity has not been shown to extend to TIMP-1 itself. Conjugating milk thistle flavonolignans, the actual source of TIMP-1 suppression, to this platform could therefore combine two complementary benefits, though this specific combination remains untested.

In this study, we developed and evaluated novel plant-based coffee substitutes produced from light- and dark-roasted milk thistle (Silybum marianum L.) seeds. The seeds exhibited a suitable composition for coffee substitute production, containing moderate protein (18.50%) and oil (14.58%) contents with low moisture (5.85%). Roasting significantly affected the color, moisture content, and volatile aroma profile of the ground products. However, the brewed beverages showed similar physicochemical properties, including soluble solids (1.2 °Brix), pH (6.45-6.46), viscosity (1.43-1.45 cP), and ash content (0.05%), indicating limited effects of roasting intensity on beverage quality. Forty volatile compounds were identified, with pyrazines, furans, pyrroles, phenols, and ketones predominating. Dark roasting enhanced the formation of pyrazines and furans, producing a more pronounced roasted aroma. Sensory evaluation identified roasted, nutty, spicy, and bitter attributes as dominant, together with distinctive herbal and cardamom-like notes characteristic of milk thistle seeds. Consumer testing demonstrated good overall acceptability for both beverages, with a slight preference for the light-roasted sample. These findings demonstrate the potential of roasted milk thistle seeds as a novel caffeine-free, plant-based coffee substitute with distinctive sensory characteristics and promising consumer acceptance.

Silybum marianum, commonly known as milk thistle, has a long history of medicinal use as a hepatoprotective plant and has emerged as a potential source of natural antimicrobial agents against multidrug-resistant (MDR) bacterial pathogens. This review provides an objective overview of current knowledge on the antimicrobial mechanisms of S. marianum and its potential utility for targeting resistant bacterial strains. Recent studies have demonstrated that silymarin, the major flavonolignan complex isolated from the seeds of S. marianum, exhibits observable antimicrobial activity against several critical MDR phenotypes, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, carbapenem-resistant Klebsiella pneumoniae, and Stenotrophomonas maltophilia. The antimicrobial effect of silymarin is concentration-dependent, with ethanolic extracts exhibiting greater antibacterial activity than aqueous extracts. The principal mechanisms underlying the anti-MDR activity of S. marianum include multiple pathways: disruption of bacterial membranes, increasing permeability; inhibition of biofilm formation; modulation of reactive oxygen species; inhibition of efflux pumps; and synergistic enhancement of conventional antibiotic activity. Advanced nanoformulation techniques have been applied to address the poor baseline bioavailability of silymarin, with nano-silymarin systems displaying lower minimum inhibitory concentrations (MICs) than conventional formulations against clinical MDR isolates in laboratory models. Topical delivery systems, such as mucoadhesive gels, offer sustained drug release profiles and enhanced permeation properties. Nevertheless, standardising extraction protocols, optimising dosing regimens, and conducting rigorous clinical trials remain essential steps to translate these preclinical findings into viable human therapeutic applications.

In dairy cows, early lactation is a period prone to oxidative stress, inflammation and health problems. Our objective was to investigate the effects of 2 strategies of nutritional supplementation on physiological and immunological status of early lactating cows. The first strategy consisted of supplementing vitamin E (all-rac-α-tocopheryl acetate) from 3 weeks before calving (3,000 IU/d before and 1,000 IU/d after calving). The other strategy consisted of supplementing plant extracts (Sambucus nigra, Salix alba, Laurus nobilis, Harpagophytum procumbens, Silybum marianum and Arctium lappa, QUALIMILK product from BIODEVAS Laboratoires, QPB plant extracts) from calving (10 g/d). In anticipation of cows being removed due to health issues or changes in calving dates, 51 Holstein dairy cows were assigned to 3 groups of 17 cows with a final target of 15 cows per group. Each group was randomly assigned to one of the 3 compared treatments: control group (final n = 15), vitamin E group (final n = 16), and QPB plant extract group (final n = 14). Their redox and immune status were monitored during the first 12 weeks of lactation, every 4 weeks. In wk 12, malondialdehyde levels in plasma tended to be lower in the vitamin E and QPB plant extract groups than in the control group. The vitamin E and QPB plant extract groups had lower ex vivo plasma CCL4, IL6 and IL8 cytokine levels, lower proportions of blood regulatory neutrophils, and less ROS production by blood neutrophils than the control group. In terms of immune response, the expression of FABP3 in milk mammary epithelial cells was downregulated in multiparous cows supplemented with vitamin E and QPB plant extracts. Therefore, supplementation with either vitamin E before and after calving or QPB plant extracts after calving clearly reduced the ex vivo inflammatory response and enhance a specific ex vivo immune response shown to be involved in the fight against mastitis.

This study investigates the valorization of the reticulated fibrous sheath covering the stems of Silybum marianum (milk thistle) as a novel lignocellulosic source for the production of cellulose nanocrystals (CNCs). A modified Kruscher-Hoffer pretreatment, followed by alkaline extraction and multi-step bleaching, was applied to isolate purified cellulose with a yield of 49.0%. Subsequent sulfuric acid hydrolysis was performed to obtain two distinct products: D2 (single-step bleaching) and D3 (two-step bleaching). CNC production through the D2 process achieved a total yield of 26.46% based on the raw material, whereas the D3 process resulted in a yield of 21.56%. Structural characterization using FTIR, XRD, SEM, and TEM confirmed the effective removal of non-cellulosic components. XRD analysis revealed high crystallinity indices of 86% and 77% for D2 and D3, respectively. Thermal analysis indicated that the D2 sample (single-step bleaching) exhibited higher thermal stability than the D3 sample (two-step bleaching), with the main degradation peak occurring at 368.1 °C, compared with 299.5 °C for D3. This difference may be related to differences in the surface chemistry of the isolated CNCs. The isolated CNCs exhibited high colloidal stability, with a maximum zeta potential of -37.7 mV, which was further supported by long-term visual observations showing no sedimentation after 30 days. Morphological observations confirmed the formation of rod-like nanocrystals, indicating the successful isolation of a CNC-rich fraction. These results suggest that Silybum marianum stem fibers represent a promising, high-yield agricultural residue for the sustainable production of reinforcing agents for bio-based composite applications.

Medicinal plants are widely used in the Mediterranean region, where they have long been employed in traditional medicine as well as in the food and beverage industry. At the same time, people in developed countries are increasingly dissatisfied with modern healthcare due to the side effects and complications associated with chemical drugs, prompting a growing interest in more natural alternative treatments. The Asteraceae family is one of the largest flowering plant families, containing many species with medicinal properties. It comprises over 1600 genera and approximately 25,000 species worldwide. Silybum marianum, Picnomon acarna, Glebionis segetum, and Carduus pycnocephalus are invasive species in the Mediterranean region belonging to the Asteraceae family. Although they have been used traditionally to treat certain diseases, their biological and pharmacological potential has not yet been fully explored. This review aims to provide a comprehensive overview of the phytochemical components, geographical and botanical characteristics, traditional uses, pharmacological activities, and potential applications of these species in green nanotechnology and the food industry.

The protective effects of herbal feed additives Withania somnifera, Silybum marianum, Centella asiatica, and silymarin (administered at feed levels of 4000 ppm, 5000 ppm, 4600 ppm, and 25,000 ppm, respectively) against the toxic effects of ochratoxin A (OTA) (administered at 2 ppm) were investigated in 48 New Zealand White rabbits (37 days old) over an 80-day experimental period. A decrease in body weight was seen in rabbits exposed to OTA alone, but that decrease was less pronounced in rabbits receiving herbal supplements. The most severe lesions in OTA-treated rabbits were found in the liver, kidneys and spleen, while milder lesions were seen in the heart, intestine and lungs. The intensity of macroscopic, histopathological and biochemical changes was highest in rabbits exposed to OTA alone, followed by rabbits additionally supplemented with herbal additives, as evidenced by histopathological findings and serum levels of blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). The most pronounced protective effects of the herbal additives were observed in the kidneys and liver. Oxidative stress was significantly increased in rabbits exposed to OTA alone, as evidenced by elevated reactive oxygen species (ROS), nitric oxide (●NO), ascorbyl radicals (●Asc), protein oxidation (PO), procollagen type I alpha 1 (COL1A1), malondialdehyde (MDA), kidney injury molecule-1 (KIM-1), hydroxyproline (Hyp), advanced glycation end products (AEGs), heme oxygenase-1 (HO-1), catalase (CAT), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well decreased superoxide dismutase (SOD) and glutathione peroxidase-1 (GPx-1) activities, while protective effects were seen for all herbal additives, and better expressed for Centella asiatica and Silybum marianum.

Unraveling alternatives to animal-based protein is an urgent global demand, and milk thistle seed protein isolate (MSPI) represents an underexploited and promising plant-based protein source for food applications. Therefore, the effects of spray (S-MSPI), freeze (F-MSPI), and oven-drying (O-MSPI) on the nutritional, physicochemical, structural, thermal, and functional attributes of MSPI have been investigated. Remarkably, F-MSPI had the highest amino acid scores in comparison with the WHO/FAO reference pattern. Morphologically, the particles of F-MSPI sample appeared as irregular porous flakes, while S-MSPI had spherical particles with smooth and uniform surfaces; however, O-MSPI showed large, compact, and aggregated particles. Structurally, O-MSPI showed significant changes compared to F-MSPI and S-MSPI, as manifested by its lower α-helix and β-sheet levels. Nevertheless, the thermal stability of O-MSPI was greater than that of F-MSPI and S-MSPI. Intriguingly, F-MSPI possessed outstanding structural integrity and functionality because of its highest foaming stability (71.7%), denaturation temperature (98.9 °C), and solubility (97.2%). In conclusion, our study underscores that F-MSPI maintains the protein's native structure and functional performance, which boosts its potential incorporation in sustainable plant-based food systems.

Silybum marianum (SM) is a rich source of flavonolignans with promising antioxidant and antidiabetic properties; however, its therapeutic application is limited by poor stability and bioavailability. This study combined experimental and computational approaches to develop and evaluate SM-loaded chitosan nanoparticles (CS-SM nanoparticles). Microwave-assisted extraction followed by LC-MS/MS profiling identified eleven metabolites, including major flavonolignans characteristic of SM. Nanoparticles prepared by ionic gelation exhibited favorable physicochemical properties, including a particle size of 173-189 nm, a polydispersity index of 0.23, a zeta potential of +41.5 mV, an encapsulation efficiency of 98%, and a drug loading capacity of 50%, indicating the formation of a stable colloidal delivery system. CS-SM nanoparticles showed enhanced antioxidant, anti-inflammatory, and α-amylase inhibitory activities compared with crude extracts. The formulation exhibited an α-amylase IC50 value of approximately 0.40 mg/mL and maintained low hemolytic activity, suggesting favorable preliminary biocompatibility. Molecular docking demonstrated favorable interactions of neosilyhermin A, silibinin, and silyhermin with α-amylase and α-glucosidase active sites. Short-timescale molecular dynamics simulations revealed ligand-dependent behavior within the chitosan-TPP matrix, indicating different release tendencies among the investigated flavonolignans. Overall, the results support CS-SM nanoparticles as a promising platform for the delivery of bioactive phytochemicals with antioxidant and antidiabetic potential.

Flavonolignans are pharmacologically important plant natural products whose production has been limited to extraction from natural sources. Their defining transformation, the oxidative coupling of flavonoid and phenylpropanoid precursors, was demonstrated to be enzyme-catalyzed. Here we show that milk thistle flavonolignans can also be assembled through an abiotic, light-driven process in vitro. Photocatalytic coupling of taxifolin and coniferyl alcohol generated the major natural flavonolignans, including silychristins, whose synthesis from native precursors has not previously been reproduced in vitro. Importantly, we identify environmental metal ions as programmable regulators of reaction outcome. Fe[3+] and Al[3+] selectively direct radical coupling toward silychristin formation, whereas Mn[2+] primarily enhances catalytic efficiency. Mechanistic analyses indicate that metal coordination of flavonoid substrates governs regioselective radical attack and molecular architecture of final products. Leveraging this principle, we establish a metal-programmable photocatalytic platform for the synthesis of both natural and new-to-nature flavonolignans. Integration of this abiotic chemistry with engineered Saccharomyces cerevisiae enabled de novo flavonolignan production directly from sugar in a one-pot photo-biohybrid process for the first time, establishing a versatile strategy for the sustainable production and diversification of flavonolignans.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and progressive pancreatic β-cell dysfunction, processes strongly influenced by adipose tissue inflammation, oxidative stress, and dysregulated lipid metabolism. Silymarin, a flavonolignan complex derived from Silybum marianum, has attracted interest as a potential adjunctive agent because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This review summarizes experimental and clinical evidence on the effects of silymarin and its major bioactive constituent, silibinin, on adipose tissue dysfunction and pancreatic β-cell injury in T2DM. Available evidence was narratively synthesized with emphasis on adipogenesis, lipid accumulation, inflammatory signaling, insulin signaling, oxidative stress, and β-cell survival. Experimental studies indicate that silymarin may reduce adipogenesis and lipid accumulation through modulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), and activation of AMP-activated protein kinase (AMPK). Silymarin may also attenuate pro-inflammatory cytokine production, enhance antioxidant defenses, and protect pancreatic β-cells from glucotoxicity-, lipotoxicity-, and cytokine-induced apoptosis. Limited clinical data suggest potential improvements in glycemic control, insulin resistance, lipid parameters, and systemic inflammation. Overall, silymarin shows promise as an adjunctive strategy for metabolic dysfunction in T2DM; however, standardized formulations and well-designed randomized clinical trials are needed to confirm its efficacy, safety, and clinical relevance.

Chicken breast meat is susceptible to lipid and protein oxidation during post-mortem processing and storage, which adversely affects its physicochemical properties, nutritional value, and market acceptability. Most existing research has concentrated on single-component plant extracts as feed additives, whereas the combined effects of multi-plant additives remain insufficiently characterized. This study evaluated the effects of two composite plant-derived feed additives (Group A: Trigonella foenum-graecum, Silybum marianum, and Ginkgo biloba; Group K: Thymus vulgaris, Cinnamomum verum, and Origanum vulgare) and their combined supplementation (Group A+K) on the quality and oxidative stability of broiler breast meat, with particular emphasis on myofibrillar protein (MP) structure and water dynamics. A total of 32,000 one-day-old Ross 308 broilers were assigned to four dietary treatments (control, A, K, and A+K) and fed for 35 d. The analyzed indicators included shear force, texture profile, water-holding capacity (WHC), MP secondary structure, oxidative markers (carbonyl and thiol contents), surface hydrophobicity, solubility, particle size, and water distribution. Group A showed the greatest tenderization response, with an approximately 50% reduction in shear force compared with the control (P < 0.05). The A+K group showed enhanced combined responses, including a 9% increase in WHC and an 8.02% decrease in carbonyl content compared with the control (P < 0.05). All treatment groups exhibited an increased MP alpha-helix proportion, reduced surface hydrophobicity and particle size, and improved solubility (P < 0.05). The A+K group also improved adhesiveness and cohesiveness. LF-NMR analysis indicated that the dietary treatments promoted a shift from free water toward immobilized water, which was associated with improved WHC. Overall, these composite plant-derived additives, especially the A+K combination, may regulate broiler meat quality through multiple targets by attenuating protein oxidation, maintaining MP structural stability, and optimizing water distribution. These findings provide a practical basis for developing plant-derived feed formulations for high-quality and oxidatively stable broiler meat.

This study aimed to investigate the physical, mechanical, morphological, crystalline structure, and thermal stability characteristics of gellan gum-pectin (GG-PC) aerogels enriched with C-dots/extract obtained from Silybum marianum petals (SME) and to evaluate the possible performance of smart biopolymers to control the peeled shrimp's freshness over 6 days at 4 ± 0.5 °C. C-dots derived from S. marianum petals presented a spherical morphology, and the particle sizes were in the quantum range of 4.19 nm - 9.91 nm (mean diameter = 7.45 ± 1.52 nm). The GG-PC + SME 2% and GG-PC + SME 2% + SiO2-doped C-dots 0.1% aerogels displayed a recognizable color change from red to dark violet, dark green, and brown when the biopolymers were subjected to pH buffer solutions of 1-6, 7, 8, and 9-10, respectively. The compressive stress, moisture content, water absorption capacity, and water vapor absorption capacity for GG-PC + SME 2%, GG-PC + SiO2-doped C-dots 0.1%, and GG-PC + SME 2% + SiO2-doped C-dots 0.1% biopolymers were significantly higher than the GG-PC group (P < 0.05), determined by 10.22-18.38 kPa, 0.42%-0.79%, 28.90%-38.56%, and 16.81%-32.20%, respectively. The peeled shrimp had a clear tendency to degrade from day 0 to day 4 (mesophilic bacterial count = 3.56 log CFU/g → 7.40 log CFU/g, total psychrotrophic bacterial count = 2.40 log CFU/g → 7 log CFU/g, total volatile basic nitrogenous compounds = 5.32 mg N/100 g → 25.33 mg N/100 g, and pH = 7 → 7.70), as the color of the GG-PC + SME 2% and GG-PC + SME 2% + SiO2-doped C-dots 0.1% aerogels on the heads of the package changed from khaki to dark violet, respectively, suggesting that intelligent biopolymers could give instant feedback on the freshness of the peeled shrimps.