Search Results (350)

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. Full article

Mycotoxin contamination of cereal-based pig feeds is a persistent threat to swine health and global pork safety. Pigs are uniquely susceptible to mycotoxicosis, and the principal toxins—aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FUMs), and ochratoxin A (OTA)—cause impaired growth, reproductive failure, hepato- and nephrotoxicity, immunosuppression, and carry-over residues in edible tissue. Anti-mycotoxin feed additives, including mineral adsorbents, biotransforming agents, and multicomponent mycotoxin-detoxifying agents (MMDAs) combining clays, phytogenic antioxidants (curcumin, silymarin), and postbiotics (yeast cell wall, hydrolyzed yeast), constitute the primary mitigation strategy. Beyond animal health, these agents play underappreciated roles in both the circular economy (CE)—enabling safe valorization of by-product feed ingredients and reducing feed waste—and in the life cycle assessment (LCA) sustainability profile of pork production, where feed conversion ratio (FCR) drives 22–95% of greenhouse gas emissions. Field-based in vivo studies in sows and weaned piglets, integrating plasma oxidative stress biomarkers (TBARS, protein carbonyls, total antioxidant capacity) with performance and reproductive endpoints, provide the most comprehensive real-world evidence for MMDA efficacy to date. This review synthesizes mycotoxin toxicology, anti-mycotoxin agent mechanisms, clinical evidence, and the CE/LCA sustainability framework, proposing integrated mycotoxin management as a One Health imperative in modern swine production. Full article

Background/Objectives: Hepatic fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition in the liver, which may progress to cirrhosis and liver failure. Short-chain fatty acids (SCFAs) have demonstrated anti-inflammatory and anti-fibrotic properties; however, their therapeutic potential in hepatic fibrosis remains incompletely understood. This study aimed to evaluate the effects of acetate, propionate, and butyrate on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in Balb/C mice. Methods: Hepatic fibrosis was induced in Balb/C mice using CCl₄, and the animals were treated with acetate, propionate, or butyrate administered via drinking water for four weeks. Biochemical parameters, histological alterations, and the expression of fibrogenic and inflammatory markers were evaluated and compared with a silymarin-treated group. Results: Treatment with SCFAs significantly reduced serum transaminase levels (AST and ALT) compared to the untreated fibrotic group. Histological analyses demonstrated the preservation of hepatic architecture and reduced inflammatory infiltrates, particularly in the butyrate-treated group. In addition, SCFAs significantly decreased the gene and protein expression of fibrogenic markers (ACTA2 and COL1A1) and inflammatory markers (NOS1, NF-κB, and IL-10), with propionate showing the most pronounced effects. Overall, the therapeutic effects observed with SCFAs were comparable or superior to those obtained with silymarin treatment. Conclusions: The findings suggest that SCFAs, especially butyrate and propionate, exert hepatoprotective, anti-inflammatory, and anti-fibrotic effects in CCl₄-induced hepatic fibrosis. These compounds represent promising therapeutic candidates for the treatment of liver fibrosis. Full article

Plant-derived compounds have recently attracted considerable scientific attention due to their potential therapeutic applications, which are largely attributed to their antioxidant properties. Tert-butyl hydroperoxide (t-BHP) is a potent inducer of intracellular oxidative stress, generating reactive free radicals, which significantly contribute to hepatic and renal damage. Micromeria frivaldszkyana (M. frivaldszkyana), a Bulgarian endemic species, contains high levels of phenolic compounds, including linarin, rosmarinic acid (RA), chlorogenic acid, rutin, quercetin, naringenin, and apigenin. In this study, male Wistar rats received oral treatment for 5 days comprising saline, 250, 400, or 500 mg/kg of M. frivaldszkyana methanolic extract, 100 mg/kg RA, or 125 mg/kg silymarin. On the final day, 0.5 mmol/kg of t-BHP was injected intraperitoneally, and blood and liver tissue samples were collected 18 h later for biochemical and histological analysis. Liver and kidney function was evaluated using biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine (Cr), uric acid (UA)), indicators of oxidative stress (malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT)), and histopathology. Exposure to t-BHP resulted in significant hepatic and renal damage, including elevated serum markers, increased lipid peroxidation, and deoxyribonucleic acid (DNA) damage. Administration of 500 mg/kg M. frivaldszkyana markedly lowered elevated serum ALT and AST levels. The extract also significantly mitigated t-BHP-induced increases in serum Cr and UA. However, no significant increase in the levels of the antioxidant enzymes SOD and CAT or in GSH was observed at all tested doses. Malondialdehyde and 8-OHdG levels increased markedly following t-BHP exposure, whereas pretreatment with M. frivaldszkyana at all tested doses significantly ameliorated these oxidative alterations. These findings suggest that the methanolic extract of M. frivaldszkyana confers protective effects against t-BHP-induced toxicity, potentially through stabilisation of cell membranes, inhibition of lipid peroxidation, and reduction in DNA damage. The extract may therefore serve as a potential natural therapeutic agent against injuries caused by oxidative stress. Full article

Chatuphalatika is a traditional Thai polyherbal formulation whose metabolically active fraction has not been identified. This study fractionated the aqueous extract (CPT) by sequential liquid–liquid partitioning to obtain solvent fractions. The ethyl acetate fraction (CPTX) had the highest total phenolic content and was enriched in hydrolyzable tannins, particularly chebulagic acid. CPTX showed the strongest inhibitory activity against HMG-CoA reductase in vitro. In vivo, C57BL/6 mice were fed a high-fat diet for 12 weeks, then treated with CPT, CPTX, or silymarin for 8 weeks while high-fat diet feeding continued. Both CPT and CPTX improved serum lipid profiles. High-dose CPTX (500 mg/kg) additionally reduced fasting blood glucose, serum ALT, and relative liver weight, without affecting body weight or adipose tissue weights. These findings indicate that phenolic enrichment concentrates the hepatic and lipid-lowering activity of Chatuphalatika. HMG-CoA reductase inhibition was used as a screening criterion to identify CPTX as the active fraction; the in vivo hepatometabolic improvements are consistent with, but do not directly confirm, modulation of cholesterol biosynthesis and hepatic lipid metabolism. Full article

Background/Objectives: Multiple sclerosis (MS) is an autoimmune neuroinflammatory disease affecting 2.9 million worldwide. Current immunosuppressive treatments offer limited neuroprotection and often cause adverse effects. Polyphenols with antioxidant and anti-inflammatory properties have been investigated as adjuncts in MS. Methods: On 19 June 2025, Embase, Medline, and ClinicalTrials.gov were systematically searched. Eligible clinical trials assessing polyphenol supplementation in MS were included. Outcomes of interest were Expanded Disability Status Scale (EDSS), annualised relapse rate (ARR), magnetic resonance imaging (MRI) changes, safety, and tolerability. Risk of bias was evaluated using the Cochrane tool, and certainty of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The protocol was registered with PROSPERO (CRD420251052042). Results: Of 870 records identified, 13 trials (n = 785) met inclusion. Nanocurcumin consistently improved EDSS in relapsing–remitting MS (3 trials, n = 150; p = 0.039–0.041), while epigallocatechin-3-gallate, silymarin (SM), cranberry extract, and bio-enhanced curcumin extract (BCM-95) curcumin showed no significant impact on disability, relapse rates, or MRI outcomes. Intervention adverse events were generally mild. SM showed potential hepatoprotective effects. Risk of bias was determined as low risk for seven of the trials and of some concern for five of the studies. Most often raising concerns because of selective reporting. Certainty of evidence, assessed using GRADE, was generally moderate, indicating some uncertainty regarding the outcomes. Meta-analysis was not possible due to the heterogeneity of included studies. Conclusions: Nanocurcumin may contribute to improvements in disability outcomes in Relapse Remitting Multiple Sclerosis (RRMS), whereas other polyphenols lack consistent efficacy. However, the evidence base remains limited by small sample sizes and methodological concerns. Larger, multicentre randomised controlled trials are required to establish optimal dosing, long-term safety, and therapeutic potential. Full article

Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg/kg) mitigates cadmium-induced toxicity (5 mg/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (−30.8%), elevated transaminases (AST, ALT; p < 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p < 0.01). Sperm concentration dropped from 75.2 to 21.8 × 10⁶/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 × 10⁶/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver/kidney biomarkers showed significant but incomplete recovery (p < 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (−8.4 kcal/mol), CAT (−8.3 kcal/mol), and SOD (−6.4 kcal/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery. Full article

Milk thistle (Silybum marianum) oil production generates substantial quantities of seed cake, an underutilized by-product with potential as a source of nutrients and bioactive compounds. This study aimed to characterize milk thistle cakes from two industrial sources (MTC1 and MTC2) and their corresponding seeds (MTS1 and MTS2), focusing on compositional properties, fatty acid profile, and antioxidant activity assessed using the DPPH scavenging assay. Proximate analysis showed that the cakes retained significant residual oil (9.26–14.51 g 100 g⁻¹) and protein (16–19 g 100 g⁻¹), with low water activity (<0.33), indicating good storage stability. Fatty acid analysis revealed a predominance of polyunsaturated fatty acids (49–52%), mainly linoleic acid (C18:2 n-6), confirming their nutritional value. Differences between industrial sources indicated variability associated with raw material and processing conditions. Extraction solvent significantly affected bioactive compound recovery from the oil fraction. Dichloromethane extracts exhibited higher total phenolic content (up to 8.87 mg GAE g⁻¹) and stronger DPPH radical scavenging activity (up to 28.07%) compared to hexane extracts, which may be attributed to a greater extraction of moderately polar phenolic compounds, including flavonolignan-type constituents potentially associated with silymarin complex. Overall, milk thistle cake represents a promising raw material for the recovery of natural antioxidants and valuable lipids, supporting its application in functional food or feed products and sustainable biorefinery processes. Full article

Background: Elevated gamma-glutamyl transferase (GGT) is a biomarker associated with alcohol-related hepatic stress and oxidative imbalance. Although alcohol abstinence is the primary determinant of GGT normalization, adjunctive strategies may support biochemical improvement in real-world settings. Methods: This non-randomized cohort study included 197 of 1957 screened participants (10.1%), stratified according to baseline GGT into 55–99 U/L (n = 95) and ≥100 U/L (n = 102). Participants in the higher baseline subgroup underwent a multimodal intervention consisting of nutraceutical supplementation (silymarin, essential phospholipids, and a polyherbal antioxidant formulation) combined with structured psychological support aimed at promoting alcohol abstinence. The primary outcome was the change in GGT between baseline (T1) and follow-up (T2). Secondary outcomes included the proportion of participants achieving GGT reduction and the magnitude of change according to baseline severity. Clinical trial registration: ClinicalTrials.gov Identifier: NCT07603726. Results: Among participants with baseline GGT ≥ 100 U/L, GGT levels decreased from a median of 133.73 to 97.41 U/L (p < 0.001), whereas in the 55–99 U/L subgroup, median GGT changed from 67.49 to 66.51 U/L without reaching statistical significance (p = 0.072). Participants in the higher baseline subgroup demonstrated greater GGT reductions (median ΔGGT: −35.25 vs. −2.58 U/L), a higher proportion achieving GGT reduction (91.2% vs. 70.5%), and higher odds of GGT reduction at follow-up in exploratory analysis (OR = 4.32, 95% CI: 1.91–9.75). Conclusions: In this real-world cohort, reductions in GGT levels were observed, particularly among individuals with elevated baseline values (≥100 U/L) who underwent the multimodal intervention. These findings support monitoring GGT dynamics in routine clinical practice, where GGT remains a practical and accessible biomarker due to its widespread availability, low cost, and sensitivity to oxidative and alcohol-related hepatic stress. Full article

Vitis coignetiae Pulliat ex Planch, commonly referred to as “meoru” in Korea (crimson glory vine), is a grape species belonging to the Vitaceae family, native to East Asia. This study investigated the protective effects of a hot water extract prepared from the vine stems of V. coignetiae (CG) in a model of CCl₄-induced acute liver injury. Mice received oral administration of CG (100, 200, and 400 mg/kg) or silymarin (200 mg/kg) once daily for 7 consecutive days, followed by intraperitoneal injection of CCl₄ (0.5 mL/kg). CG attenuated CCl₄-induced oxidative stress, as indicated by reduced hepatic malondialdehyde production and decreased 4-hydroxynonenal-positive cells. These effects were accompanied by restoration of antioxidant defense systems, including increased glutathione levels and superoxide dismutase and catalase activities, along with increased nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression. Hepatic inflammatory responses were also attenuated by CG treatment, with reductions in TNF-α, interleukin (IL)-1β, and IL-6 levels, inflammatory cell infiltration, and nuclear factor-κB (NF-κB) mRNA expression. Furthermore, CG attenuated apoptotic cell death, as evidenced by decreased cleaved caspase-3-positive and cleaved poly(ADP-ribose) polymerase (PARP)-positive cells. CG also lowered serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase levels, and alleviated hepatocellular degeneration in histopathological analysis. Collectively, these findings suggest that CG may exert protective effects against CCl₄-induced liver injury by regulating oxidative stress, inflammation, and apoptosis. Full article

Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research. Full article

In the context of modern ruminant nutrition, increasing attention is being directed toward the valorization of agro-industrial by-products as alternative feed ingredients that enhance nutrient utilization efficiency while supporting the sustainability of animal production systems. Milk thistle (Silybum marianum) oilseed cake, a by-product of oil extraction, has emerged as a resource of growing interest due to its favorable nutritional profile and the presence of bioactive compounds with functional properties. This review critically analyzes recent scientific literature addressing the use of milk thistle oilseed cake in ruminant nutrition, highlighting its potential practical relevance as a functional feed ingredient. The available evidence suggests that milk thistle oilseed cake may support inclusion in ruminant diets at moderate levels; however, controlled in vivo studies remain limited, and several proposed mechanisms are inferred from studies on structurally analogous polyphenol-rich by-products rather than from milk thistle cake itself. Further research is needed before precise inclusion recommendations can be established. Special attention is given to the bioactive fraction dominated by the silymarin complex, which may interact with rumen digestive and fermentative processes, influencing nutrient utilization efficiency and oxidative stability. Overall, the findings suggest that milk thistle oilseed cake represents a promising feed resource that aligns with sustainable and efficiency-oriented feeding strategies in modern ruminant production systems. Full article

Dexamethasone induces systemic toxicity, including oxidative stress, inflammation, hematological disturbances, and organ damage, particularly in the lungs and thyroid. Taurine exhibits antioxidant and anti-inflammatory properties, but poor bioavailability limits its efficacy. Nanoparticle delivery may enhance stability and tissue targeting. This study aimed to evaluate the protective effects of taurine-loaded chitosan nanoparticles (Tau–CS NPs) against dexamethasone-induced tissue injury in rats. Forty-eight male Wistar rats were allocated into control, DEXA, DEXA + silymarin, DEXA + taurine, and DEXA + Tau–CS NPs groups. Tau–CS NPs were characterized by TEM, UV–vis, FTIR, encapsulation efficiency, and drug loading. Hematology, oxidative stress markers (CAT, SOD, GSH, MDA), thyroid hormones (T3, T4, TSH, calcitonin), protein profile, lung and thyroid histopathology, and MPO expression were assessed. Tau–CS NPs showed uniform spherical morphology (11–60 nm), high encapsulation (98.2%), and substantial loading (50.36%). Dexamethasone caused hematological, oxidative, thyroidal, and histological disturbances. Tau–CS NPs markedly restored hematological indices, antioxidant defenses, thyroid function, protein profile, and tissue architecture, outperforming free taurine and silymarin. MPO expression was significantly reduced, indicating decreased inflammation. Taurine nanoparticles effectively mitigate dexamethasone-induced systemic and organ-specific toxicity, offering improved bioavailability and targeted delivery, highlighting their therapeutic potential. Full article

Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H₂O₂ relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin. Full article