Search Results (4,470)

This study investigated the effects of graded dietary barley replacement for corn on growth performance, rumen fermentation, carcass traits, meat quality, fatty acid profiles, and the rumen microbiome in Arbas White Cashmere goats, and further applied untargeted muscle metabolomics to elucidate the metabolic mechanisms underlying meat quality alterations. Growth performance was monitored for all goats (n = 10 per group); rumen fermentation, carcass traits, serum biochemistry and meat quality were determined in six randomly selected goats per group (n = 6); and rumen microbiota profiling and muscle metabolomics were performed on three selected goats per group (n = 3). Partial barley substitution (33% and 67% of starch from barley) significantly improved final body weight and average daily gain (p < 0.05), whereas total replacement (100% barley starch) did not confer additional growth advantages. Moderate barley inclusion increased ruminal propionate concentration (p = 0.001) and enriched the fiber-degrading bacterium Prevotella, while total barley replacement markedly reduced rumen microbial diversity (Sobs, Chao1, ACE, and Shannon indices; p < 0.01) and depleted multiple fibrolytic and hydrogenotrophic genera, including Christensenellaceae_R-7_group, NK4A214_group, and Methanobrevibacter. The 33% barley group exhibited elevated serum total bile acids, FGF-19, and CYP27A1 levels (p < 0.05), suggestive of modulated bile acid metabolism, along with decreased glucose-6-phosphatase (p < 0.05), pointing to suppressed hepatic gluconeogenesis. Muscle metabolomics revealed that moderate barley substitution predominantly affected glycerophospholipid metabolism, with upregulation of PE(P-18:1/20:4) and PC(16:0/16:0), whereas total replacement induced extensive metabolic reprogramming characterized by downregulation of glycine and glutathione-related metabolites, indicative of compromised antioxidant defense. The 33% barley group also exhibited the highest muscular C18:3n-3 content (p < 0.01), while the 67% and total replacement groups showed increased C22:6n-3 deposition (p < 0.05). Correlation analysis confirmed that PE(P-18:1/20:4) and PC(16:0/16:0) were significantly positively correlated with ruminal propionate and ADG (r = 0.841–0.986; p < 0.05), and Prevotella abundance showed a strong negative trend with G-6-Pase (r = −0.771). Collectively, these findings demonstrate that replacing one-third of dietary corn starch with barley starch optimally balances productivity, rumen health, and meat quality through enrichment of Prevotella, enhanced propionate production, and modulation of bile acid metabolism, while excessive barley inclusion destabilizes the rumen ecosystem and triggers muscle oxidative stress, providing a theoretical basis for precision grain formulation in intensive cashmere goat production. Full article

Antimicrobial resistance is a growing global health challenge, highlighting the need for new bioactive compounds from medicinal plants. Vepris nobilis is traditionally used in East Africa for treating infections and respiratory disorders; however, its essential oil (EO) composition and antimicrobial mechanisms remain poorly characterized. This study investigated the chemical composition and antimicrobial activity of V. nobilis EO, along with an in silico evaluation of its major constituent, germacrene D. The EO was extracted by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC–MS). Its antimicrobial activity was evaluated against 26 bacterial and 4 fungal strains using disc diffusion, broth microdilution, and MBC/MFC (Minimum Bactericidal Concentration/Minimum Fungicidal Concentration) assays. Germacrene D showed stronger activity than the EO, particularly against both multidrug resistant (MDR) and non-MDR Gram-negative bacterial strains (MIC = 10 µg/mL), with bactericidal and fungicidal effect. Molecular docking of germacrene D against two clinically relevant enzymes—dehydrosqualene synthase (CrtM) from Staphylococcus aureus and SWISS-modeled sterol 14-α-demethylase (CYP51) from Penicillium funiculosum—suggested potential interactions with both targets, with a favorable predicted binding affinity for CrtM (−7.654 kcal/mol) and for CYP51 (−5.898 kcal/mol). These findings provide preliminary insights into a possible antimicrobial mechanism, although experimental validation is needed to confirm this hypothesis. ADMET analysis suggested favorable drug-like properties despite limited solubility. These findings provide scientific support for the traditional use of V. nobilis leaves in the treatment of respiratory infections and highlight germacrene D as a promising lead compound for further antimicrobial development. Full article

In total, 37–39% of prepubertal patients present with cancer cells in their testes at the time of diagnosing a hematologic malignancy, and elimination of cancer cells from immature testicular tissue (ITT) remains unsuccessful. Treating testicular single-cell suspensions (TCSs) with chemotherapy before generating testicular organoids (TOs) for in vivo maturation after transplantation could be considered to safely restore fertility with cryo-stored ITT. Five different enzymatic digestion protocols (E1 to E5) were compared but did not show significant differences. For subsequent experiments, E3 using 1.4 mg/mL DNase I and 0.5 mg/mL Liberase was chosen based on the highest recovery of viable testicular cells per mg of tissue and lowest enzymatic concentrations. TCSs were contaminated with a human leukemia HL-60 cell line at concentrations of 4 or 10% and exposed for 24 h to cisplatin (1 µM or 3 µM) or carboplatin (10 µM or 30 µM) prior to TO generation and compared to controls. After eighteen days, hematoxylin and eosin staining showed the development of TOs with forming seminiferous tubules (STs) and interstitium in all conditions. Chemotherapy-treated TOs showed altered germ cell (GC) (DDX4⁺) and somatic (ACTA2⁺, CYP11A1⁺) cell-type-specific location. CD43⁺ HL-60 cells were located outside forming STs in untreated TOs, while in chemotherapy-treated TOs, HL-60 cells were found inside and outside STs. Cancer cell numbers were significantly reduced in 30 µM carboplatin, showing a 3.7-fold reduction, whereas 10 µM carboplatin, 1 µM and 3 µM cisplatin did not demonstrate a statistically significant reduction. DDX4⁺ GC numbers were not statistically reduced after cisplatin or carboplatin exposure. Chemotherapy did not significantly reduce somatic cell numbers. As substantial residual cancer cell contamination remained, it is unlikely that short-term cisplatin/carboplatin treatment as a stand-alone purging strategy will achieve adequate decontamination for a safe fertility restoration approach. Future research should focus on exploring other chemotherapeutic drugs and/or combinations and elucidating the mechanism of chemotherapy-induced altered TO generation. Full article

Objectives. To identify associations between CYP3A4*22 and CYP3A5*3 genotypes, CYP2D6 phenotype, and the effectiveness and safety of antipsychotics in neurotypically developed boys with conduct disorders. Methods: The study included neurotypically developed boys aged 7–12 years who were hospitalized for conduct disorders. All patients were prescribed an antipsychotic. Patient follow-up lasted 14 days. Treatment effectiveness was assessed using a clinical aggression assessment (checklist) and the CGI-S, CGI-I, and CGAS scales. Safety was assessed using the UKU SERS and SAS scales. Patients were examined upon enrollment in the study, on day 5, and on day 14. All patients were genotyped for the CYP3A4*22 (rs35599367, C>T), CYP3A5*3 (rs776746, 6986T>C) CYP2D6*3 (rs35742686), CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (rs28371725) loci. CYP2D6 metabolism type was determined based on genotyping results, and patients were divided into two subgroups: those with normal metabolism (NM) and those with intermediate or poor metabolism (IM + PM). Results: Patients taking carbamazepine (n = 11) were excluded from the analysis of associations between treatment outcomes and the CYP3A4*22 and CYP3A5*3 polymorphisms. The analysis of associations between treatment outcomes and CYP2D6 metabolism type was conducted in two stages: the overall sample and a subsample of patients who were prescribed risperidone (n = 80). No significant associations were found between carrier status of the CYP3A4*22 and CYP3A5*3 polymorphisms and treatment effectiveness parameters. Analysis of the overall sample did not reveal any significant associations between CYP2D6 metabolism subtypes and the effectiveness parameters of drug therapy. Analysis of patients receiving risperidone revealed one statistically significant association: patients with CYP2D6 IM + PM reported headaches more frequently (16.1% vs. 2%; p = 0.03). Carrier status of the CYP3A4*22 polymorphism was significantly associated with asthenia and lethargy on day 5 (50% vs. 9.4%; p = 0.008). Conclusions: Our study identified only a few significant associations between the CYP3A4*22 polymorphism, CYP2D6 slow metabolism, and patients’ reports of early adverse reactions in a 14-day observation period. Further research is needed to identify pharmacogenetic predictors of the efficacy and safety of antipsychotics in neurotypical children with conduct disorders. Full article

As metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) grow increasingly prevalent, it is essential to improve understanding of the contributing factors and how these conditions may interact. Metabolic and alcohol-related liver injury frequently co-occur, prompting the introduction of the term metabolic dysfunction and alcohol-associated liver disease (MetALD) to describe individuals with MASLD who also consume significant amounts of alcohol. Among the exposures relevant to MetALD, dietary fructose is of particular interest because it shares multiple mechanisms of hepatotoxicity with alcohol. This review synthesizes current evidence for hepatotoxic interactions, emphasizing areas most relevant to MetALD pathogenesis. Epidemiologic data indicate substantial overlap between populations with high fructose and alcohol exposure, while clinical studies increasingly associate combined exposure with greater fibrosis progression and adverse liver outcomes. Several mechanistic pathways have been shown to overlap in terms of their interactions with fructose and ethanol, including endogenous fructose generation, cytochrome P450 2E1 (CYP2E1) induction, mitochondrial dysfunction, dysregulated lipid metabolism, uric acid-driven inflammasome signaling, and disruption of the gut–liver axis. Emerging evidence suggests that these pathways interact in ways that may amplify injury beyond the effects of either exposure alone. Greater integration of the alcohol and metabolic liver disease fields will be necessary to clarify mechanistic interactions, determine risk factors, and develop effective interventions for this increasingly common form of liver injury. Full article

California’s Proposition 65 requires warning labels for chemicals associated with carcinogenicity or reproductive toxicity, affecting global cosmetic and fragrance formulations. While safrole has an established safe harbor level (No Significant Risk Level, NSRL) of 3 µg/day, its structural analogues, estragole and methyleugenol, lack specific safe harbor thresholds. To address this data gap using non-animal methodologies, this study evaluated a Next-Generation Risk Assessment (NGRA) workflow combining read-across and in silico modeling. Structural, physicochemical, and skin-permeation profiling supported category homogeneity (Tanimoto Tc ≥ 0.82 and comparable log Kp values) in accordance with OECD and ECHA guidelines. Multi-platform QSAR consensus (ToxTree, Danish QSAR, and VEGA QSAR) indicated that while parent phenylpropenes lack direct bacterial mutagenicity, they share a hepatic bioactivation pathway leading to mammalian clastogenicity and carcinogenicity predictions. Molecular docking with human Cytochrome P450 1A2 (CYP1A2; PDB: 2H14) identified safrole as the category’s conservative toxicological benchmark, exhibiting the highest binding affinity (−8.026 kcal/mol) and closest proximity to the catalytic HEME iron. Consequently, applying safrole’s 3 µg/day NSRL to estragole and methyleugenol provides a quantitative threshold to evaluate consumer exposure in cosmetic products, ensuring public health protection and regulatory compliance. Full article

Background/Objectives: Individuals with 46,XY disorders of sexual development (DSD) present with incomplete genital masculinization, aberrant gonadal development, and occasional retention of Müllerian duct remnants. Genetic factors play a substantial role in DSD pathogenesis, and whole-exome sequencing has expanded the catalog of candidate variants in recent years. However, the underlying molecular pathways remain incompletely characterized, and the functional relevance of most isolated genetic findings has not been systematically determined. This study aimed to identify and functionally characterize novel NR5A1 variants in DSD. Methods: A heterozygous missense variant NR5A1 c.88T>A (p.Cys30Ser) was identified in two patients with DSD, and initial functional characterization of the variant was performed via immunofluorescence analysis, Western Blotting, RNA sequencing, and quantitative real-time PCR analysis. Results: Wildtype NR5A1 protein localized predominantly to the nucleus, whereas the p.Cys30Ser mutant exhibited dual nuclear and cytoplasmic distribution. Compared with the wildtype, the p.Cys30Ser variant altered the expression of 642 genes, with differentially expressed genes primarily enriched in the neuroactive ligand–receptor interaction pathway. The variant impaired the transactivation of canonical NR5A1 downstream targets, resulting in the marked downregulation of 560 genes including key regulators such as KISS1R, CYP11A1, STAR, GABRP, and GRAMD1D. Conclusions: This study is the first to identify and functionally characterize the NR5A1 p.Cys30Ser variant in the context of DSD. Our findings broaden the mutational spectrum of NR5A1-related DSD and provide new insights into the molecular genetic basis of sexual development disorders. Full article

Objective: Saline–alkali stress (composed of neutral and alkaline salts) severely constrains soybean productivity. Although nicotinamide can enhance plant salt tolerance, its most effective concentration and molecular basis in soybean remain unclear. This study aimed to systematically investigate the regulatory effect of exogenous nicotinamide on soybean saline–alkaline tolerance and to identify its candidate genes and putative mechanisms under salt-stressed conditions. Methods: Soybean cultivar ‘Hefeng 25’ seedlings were exposed to 200 mmol/L mixed salt stress and treated with nicotinamide at 0 (CK), 10, 50, and 200 mg/L. Growth parameters, ROS levels, ion contents, photosynthetic pigments, osmoregulatory substances, and antioxidant enzyme activities were measured. Transcriptome sequencing and RT-qPCR were performed to identify differentially expressed genes (DEGs), followed by enrichment analysis. Results: Exogenous nicotinamide significantly improved soybean saline–alkaline tolerance relative to the salt-stressed CK group, with 50 mg/L (SA2) showing the most pronounced physiological improvements among all tested concentrations. SA2 treatment enhanced plant height, biomass, K+ content, and antioxidant enzyme activities while reducing Na+ accumulation and ROS levels compared with CK. Transcriptome analysis identified PM1 as the shared gene across the five non-most effective comparisons. Enrichment analysis implicated DEGs primarily in ko03110 (chaperones and folding catalysts), ko00199 (cytochrome P450), and ko04141 (protein processing in the endoplasmic reticulum). RT-qPCR confirmed that PM1, P450 genes (CYP74A1, CYP83D1), HSPs (HSP23, HSP18), and ROS scavengers (NAC1, GSTU43) were upregulated under non-most effective doses (SA1/SA3) but downregulated to levels comparable to the stressed CK in SA2; conversely, SA2 specifically restored the expression levels of stress-repressed WRKY57 and LBD15. Transcriptomically, SA2 exhibited a profile most similar to the saline–alkali-stressed CK group, with the fewest number of differentially expressed genes among all treatments, whereas non-optimal nicotinamide concentrations were associated with extensive transcriptional changes in ER protein processing, detoxification-related, and oxidative stress-related pathways. The limited transcriptional changes in SA2 indicate greater transcriptional similarity to the stressed control, which paralleled its superior physiological performance. Conclusions: Nicotinamide effectively alleviates soybean saline–alkaline stress at 50 mg/L, with the most significant physiological benefits and the fewest transcriptional changes relative to the stressed control. The non-most effective nicotinamide concentrations show extensive stress-related transcriptional reprogramming in protein folding, detoxification, and stress-response pathways relative to the salt-stressed control, putatively implicating ER stress, detoxification, and oxidative stress-related responses at the transcript level, with PM1 acting as a potential candidate transcriptional marker of dose-dependent transcriptional regulation under saline–alkali stress. Full article

Plasma prorenin is commonly elevated in patients with diabetes and has been associated with the development of albuminuria and progression of diabetic nephropathy. Because albuminuria often reflects podocyte injury, the pathogenic role of prorenin in podocyte dysfunction warrants further investigation. In this study, we examined the association between prorenin and podocyte injury, as well as glomerular fibrosis, using a transgenic rat model in which prorenin is inducibly expressed and secreted from the liver. cyp1a1-prorenin transgenic rats were randomized to receive diets containing increasing concentrations of the gene activator indole-3-carbinol (I3C; 0.05%, 0.15%, or 0.3%) for 4 weeks. Wild-type rats maintained on a normal diet served as controls. I3C administration resulted in a dose-dependent increase in plasma prorenin levels in transgenic rats. Elevated prorenin was associated with increased mean arterial pressure and urinary albumin excretion, accompanied by a dose-dependent reduction in podocyte number and slit diaphragm protein expression, as well as segmental foot process effacement and podocyte hypertrophy. In addition, increased prorenin stimulated renal expression of profibrotic factors and promoted glomerular fibrosis. Treatment with either amlodipine or enalapril for 6 weeks prevented the development of hypertension and partially attenuated podocyte injury, albuminuria, and renal fibrosis, without fully reversing these changes. These protective effects were associated with suppression of NF-κB- and Nox2-mediated inflammatory and oxidative stress pathways. Collectively, these findings demonstrate that prorenin promotes podocyte injury and glomerular fibrosis through mechanisms that are partially dependent on hypertension and angiotensin II but also involve angiotensin II-independent pathways. Full article

This study investigated dietary effects of rosmarinic acid (RA) on the growth and immunity of Litopenaeus vannamei, and performed hepatopancreatic transcriptomic analysis to explore potential underlying molecular associations. RA was added to basal diet at 0 mg/kg (RA0), 50 mg/kg (RA50), 150 mg/kg (RA150), and 450 mg/kg (RA450) to feed L. vannamei (1.80 ± 0.03 g) for 8 weeks. The RA450 group exhibited higher weight gain and a lower feed conversion ratio than the control (p < 0.05). Serum ACP and ACH50 activities in all RA-supplemented groups (RA50, RA150 and RA450), as well as AKP and LZM activities in the RA150 and RA450 groups, were significantly higher than those in the control (p < 0.05). The RA150 and RA450 groups also showed higher T-AOC, R-cell count, lower MDA content in hepatopancreas, and greater intestinal villus width and muscular thickness than the control (p < 0.05), as well as lower mortality in Vibrio parahaemolyticus challenge (p < 0.05). Transcriptomic analysis showed that DEGs in the three RA-supplemented groups were enriched in metabolism pathways such as arachidonic acid, glycosaminoglycan degradation, fatty acid biosynthesis and peroxisome. Among them, growth-related genes (cyp2l, hexb, hacd) and immune/antioxidant genes (ddo, xdh, npc2, galst, gst3) were upregulated by dietary RA. In summary, dietary RA improved the growth, immune and antioxidant functions of L. vannamei and its resistance to V. parahaemolyticus. The improvements were associated with transcriptional changes in lipid-metabolism-related pathways and immune/antioxidant-related genes. These findings provide a theoretical basis for the application of rosmarinic acid as a green additive in the sustainable aquaculture of L. vannamei. Full article

Background/Objectives: Microbial biotransformation of monoterpenoids is a promising approach for obtaining bioactive compounds. Rhodococcus species are attractive biocatalysts due to their metabolic versatility and ability to transform hydrophobic substrates. In this study, we investigated the catalytic potential of Rhodococcus qingshengii IEGM 267 toward carveol isomers and explored genomic features that may underlie this activity. Methods: The strain was cultivated in mineral medium supplemented with (−)-trans-carveol. Biotransformation products were analyzed by TLC and GC–MS. The draft genome was sequenced, assembled, taxonomically assigned, and annotated using standard bioinformatics tools. Results: Rhodococcus qingshengii IEGM 267 efficiently converted (−)-trans-carveol to carvone. Genome analysis confirmed the taxonomic assignment of the strain and revealed a large repertoire of oxidoreductases, including monooxygenases, hydroxylases, and dehydrogenases. Seven genes encoding cytochrome P450-dependent oxygenases were identified as candidate enzymes potentially involved in carveol oxidation. Conclusions: R. qingshengii IEGM 267 is an efficient and stereoselective biocatalyst for (−)-trans-carveol oxidation. The results of bioinformatics analysis suggest an alternative enzymatic basis for this transformation and provide a foundation for future functional characterization. Full article

Plants are continuously exposed to volatile organic compounds (VOCs) emitted by neighbors. Although the mechanisms governing VOC uptake and metabolism remain unclear, cytochrome P450 monooxygenases (CYP450s) are thought to participate in the detoxification and metabolic conversion of absorbed VOCs. Data from previously conducted cDNA microarray transcriptomic profiling in potato exposed to French marigold essential oil (FM-EO) was here used to filter differentially expressed sequences, and identified 54 unique CYP450 transcripts. Among the 10 most highly expressed sequences, two CYP81D1-like (81D1-1 and 81D1-2) and one CYP81D11-like (81D11-1) transcripts were found. RT-qPCR confirmed their strong induction within 8 h of volatile exposure. Comprehensive bioinformatics identified the most highly induced 81D1-1 gene as a CYP450 containing a predicted N-terminal hydrophobic signal or membrane-anchor region, the conserved heme-binding signature motif, and regulatory elements associated with oxidative stress responses. The other 81D11-1 gene, exhibiting a comparable expression level, was annotated only as a heme-binding protein but possessed seven distinct cis-regulatory elements, suggesting high transcriptional plasticity. Machine learning predictions assigned the highest interaction probability to (Z)-β-ocimene, whereas structure-based docking yielded the most favorable mean score for piperitone. This study provides the first characterization of the potato CYP450 superfamily in the context of volatile-mediated plant–plant interactions and identifies two CYP81D members as strong candidates for the oxidative metabolism of absorbed VOCs. The results support a proposed detoxification pathway in which CYP81-mediated oxidation precedes glutathione conjugation and intracellular sequestration of VOCs. These candidate genes provide a valuable foundation for future functional studies and may facilitate the development of sustainable crop protection strategies based on volatile-mediated plant defense. Full article

Background/Objectives: In the search for potent non-sugar α-glucosidase inhibitors with improved safety profiles, a novel flavonoid glycoside was isolated for the first time from the stem bark of Albizia saponaria (Fabaceae). The objective of this study was to elucidate its chemical structure and evaluate its therapeutic potential as an anti-hyperglycemic agent compared to known related flavonoids and a standard clinical drug. Methods: Comprehensive structural elucidation was performed using high-resolution mass spectrometry and multidimensional 1D/2D NMR (¹H, ¹³C, HSQC-DEPT, COSY, and CIGAR). To assess its inhibitory efficacy and pharmacokinetic profiles, an in silico comparative study was conducted against a database of related flavonoids (Quercitrin, Hyperoside, and Isoquercitrin) and the clinical drug Acarbose. This involved molecular docking simulations against human intestinal maltase-glucoamylase (PDB ID: 3TOP) alongside integrated ADMET modeling and toxicological screening. Results: The compound was successfully identified as 4′,7-dihydroxyflavan-3′-O-β-D-glucoside (1). Molecular docking revealed that Compound 1 exhibited a superior predicted binding affinity of −9.5 kcal/mol, outperforming Quercitrin (−9.3 kcal/mol), Hyperoside (−8.3 kcal/mol), Isoquercitrin (−7.9 kcal/mol), and Acarbose (−7.2 kcal/mol). This strong thermodynamic stability is driven by a robust conventional hydrogen-bonding network with key active site residues (Arg1377, Gln1372, and Gly1365), successfully overriding a localized electrostatic strain at Asp1279. Furthermore, ADMET modeling demonstrated a highly desirable local pharmacokinetic framework; its low Caco-2 permeability (−6.432) and low human intestinal absorption (HIA = 0.120) favor targeted luminal retention in the gastrointestinal tract, mirroring Acarbose while minimizing systemic exposure. Crucially, toxicological screening unveiled a significant safety advantage for Compound 1, marked by negligible CYP3A4 interaction (0.004) and a remarkably low risk of Drug-Induced Liver Injury (DILI = 0.213) compared to the high-risk hepatotoxic profile of Acarbose (DILI = 0.882) and the reference flavonoids (DILI > 0.69). Conclusions: These predictive findings establish Compound 1 as a highly promising, low-toxicity natural scaffold for anti-hyperglycemic drug development. Its superior binding affinity and minimized hepatotoxicity risk warrant subsequent in vitro and in vivo functional validation. Full article

This study evaluated graded dietary supplementation with sterol-enriched yeast hydrolysate (SYH) in late-laying yellow-feathered broiler breeder hens. A total of 720 55-week-old hens received 0, 0.2, 0.5, or 0.8 g/kg of SYH for six weeks after a one-week adaptation period. SYH is a composite product containing sterols, mannan, nucleotides, and amino nitrogen; therefore, the observed effects cannot be attributed to sterols alone. Eggshell strength increased at 0.5 and 0.8 g/kg, whereas fertility and hatchability were unaffected. The 0.5 g/kg group showed the highest ovarian index values and the greatest quantities of 5–12 mm yellow follicles. The 0.8 g/kg group showed the highest serum reproductive hormone and immunoglobulin concentrations, together with the highest reactive oxygen species and cytokine concentrations. Hepatic and ovarian superoxide dismutase activity increased selectively, whereas most other antioxidant indices were unchanged. Ovarian FSHR, CYP19A1, and VDR mRNA expression showed concentration-specific patterns. The strongest peripheral endocrine response at 0.8 g/kg did not coincide with the most favorable ovarian developmental response. Under the conditions of this study, 0.5 g/kg represents a candidate inclusion concentration for further validation rather than a confirmed optimum. Full article

Valerian (Valeriana officinalis L.), passionflower (Passiflora incarnata L.), and ginkgo (Ginkgo biloba L.) are among the most widely used medicinal plants in European phytotherapy, with well-documented traditional use for anxiety, insomnia, cognitive decline, attention-deficit/hyperactivity disorder (ADHD), and Parkinson’s disease. This narrative review critically analyses available clinical, pharmacological, toxicological, and regulatory data on these three species in the context of central nervous system (CNS) disorders. A comprehensive literature search was conducted in PubMed, Scopus, and the Cochrane Library; regulatory documents from the European Medicines Agency (EMA), the European Scientific Cooperative on Phytotherapy (ESCOP), and the World Health Organization (WHO) were also included. Valerian showed the most consistent clinical evidence for an improvement in sleep quality and reduction in anxiety. Passionflower demonstrated anxiolytic and mild sedative effects in several controlled trials. Ginkgo showed clinically relevant benefits in mild cognitive impairment, dementia, and vertigo. All three plants exhibited acceptable safety profiles at the recommended doses; however, significant drug interactions were identified, notably ginkgo’s inhibition of CYP2C19 and antiplatelet effects, and valerian’s potentiation of CNS depressants. Regulatory frameworks across EU member states remain inconsistent. Further high-quality randomized controlled trials with standardized extract characterization are needed. Full article