Search Results (2,376)

Scrophularia aestivalis Griseb. is a Balkan endemic species whose phytochemical composition and medicinal properties have not been previously investigated. The therapeutic potential of Scrophularia species has attracted considerable attention, resulting in extensive studies on their chemical and pharmacological properties, with over 200 secondary metabolites identified to date. The present study aimed to explore the phytochemical composition of Bulgarian-origin S. aestivalis, including isolation and characterization of individual secondary metabolites. From methanol extract of the plant’s aerial parts, aucubin, harpagide, 8-O-acetylharpagide, cis- and trans-harpagoside, 6-O-methyl catalpol, acylated derivatives of catalpol, and linarin were isolated and identified. The anti-obesity activity of the extract and primary fractions was evaluated in a Caenorhabditis elegans model of obesity. Significant lipid-reducing activity was demonstrated in four fractions, indicating promising anti-obesogenic properties. Following chemical profiling and quantitative analysis, the main components of the most active fractions were identified, namely the cis- and trans-harpagoside isomers. Subsequent experiments demonstrated that treatment with harpagoside reduced lipid accumulation and improved mitochondrial function in glucose-supplemented worms, with the data suggesting potential involvement of the SKN-1 signaling pathway. Full article

Dalbergia odorifera, a rare and precious medicinal plant, has been used to treat cardio- and cerebrovascular diseases in China for thousands of years. D. odorifera heartwood (DOH) is usually considered to be the main part used for medicine, and other parts (leaf, DOL; flower, DOF; pod, DOP) of D. odorifera are neglected. In this paper, a systematic comparative study was conducted on phytochemicals and antioxidant properties of four parts of D. odorifera. A total of 72 volatile organic compounds (VOCs) and 820 nonvolatile organic compounds (NVOCs) were identified in four D. odorifera parts by GC-MS and UPLC-ESI-Q/TRAP-MS/MS, respectively. Differences in phytochemical profiles among the different parts were observed. DOH exhibited a significantly different level of trans-nerolidol and flavonoids compared to the other parts. Taking into account all the parameters measured, methanolic extracts of DOH, DOL, and DOF had good antioxidant activity, with the highest value in DOH, followed by DOL and DOF. Moreover, the strong antioxidant activity of the methanolic extract may be related to the flavonoid components. The results indicated that DOL and DOF also have potential for further development and utilization. Full article

Aristolochic acid I (AAI) is widely recognized as a genotoxic and cytotoxic compound. To rationally propose detoxification strategies, it is essential to fully elucidate the in vivo disposition of AAI. Nevertheless, the toxicokinetic characteristics of AAI, particularly the possible involvement of the recirculation process, remain incompletely understood. In this research, toxicokinetics of AAI was studied following a single oral administration of AAI in Fisher rats (10, 30 and 100 mg/kg, n = 6). A method of ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was developed to achieve the quantitation of AAI in rat plasma. Plasma concentration–time profiles and kinetic parameters were analyzed to characterize the toxicokinetic behavior of AAI. A secondary elevation was observed in the plasma concentration–time profiles of AAI, suggesting the existence of AAI reabsorption. The non-linear elimination kinetics of AAI might be attributed to capacity-limited excretion via bile. Additionally, the biliary excretion of AAI and several key metabolites was also explored through qualitative analysis of bile samples. For the first time, AAI-O-glucuronide was identified in bile, providing further support for enterohepatic recirculation (EHR)-mediated reabsorption of AAI. In conclusion, these findings provided solid evidence for EHR-mediated reabsorption of AAI in rats. The recirculation process might be a key mechanism responsible for the prolonged retention of AAI. In the future, detoxification strategies targeting the EHR process could be effective approaches to minimize the systemic exposure of AAI. Full article

Objectives: This study aimed to elucidate the determinants of interindividual variability in the pharmacokinetics of ibrutinib among healthy Chinese subjects, focusing on the influence of demographic characteristics, dietary conditions, and genetic polymorphisms on CYP enzymes and ABC transporters. Methods: Thirty-two participants were randomly assigned to either a fasting (n = 16) or fed (n = 16) group, each receiving a single 140 mg oral dose of ibrutinib. Plasma concentrations were quantified using a validated UPLC–MS/MS method. Genetic polymorphisms in CYP3A4, CYP3A5, CYP2D6, and ABCG2 were identified by Sanger sequencing. Pharmacokinetic parameters, including apparent clearance (CL/F), maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0-t), and time to maximum concentration (Tmax), were estimated by non-compartmental analysis and statistically evaluated for associations with demographic, dietary, and genetic variables. Results: Food intake significantly affected ibrutinib pharmacokinetics, with postprandial administration resulting in reduced CL/F and increased Cmax and AUC0-t (p < 0.01). Gender differences were also observed, as females exhibited higher CL/F, lower Cmax, and AUC0-t than males (p < 0.05). The CYP2D6 c.100C>T polymorphism significantly decreased CL/F and increased exposure in fasting and male subjects (p < 0.05), but this effect was absent under fed conditions. Conversely, the ABCG2 c.421C>A variant was associated with increased CL/F and decreased AUC0-t (p < 0.05), while other genotypes exerted negligible effects. Conclusions: Ibrutinib pharmacokinetics are significantly modulated by dietary status, gender, and genetic polymorphisms, particularly CYP2D6 c.100C>T and ABCG2 c.421C>A. These findings underscore the importance of integrating pharmacogenetic and physiological factors into individualized dosing strategies to optimize therapeutic efficacy and minimize adverse effects. Full article

Background: PAL genes are crucial for plant growth and stress response, yet studies on the PAL gene family in Camellia nitidissima are sparse. Methods: The PAL gene family was screened from the entire genome of C. nitidissima, and their physicochemical properties, chromosomal locations, intraspecific and interspecific collinearity, conserved motifs, phylogenetic trees, cis-acting elements, and gene structures were analyzed. The expression patterns of the CnPAL genes were compared across different tissues, and the highly expressed CnPAL1 gene was expressed in prokaryotes, and its enzyme activity was validated using UPLC-MS technology. Results: The results revealed that six CnPALs were identified in the C. nitidissima genome, distributed unevenly across six chromosomes. The CnPAL proteins shared similar physicochemical properties, with highly conserved motifs and gene structures. Promoter analysis showed multiple cis-acting elements in the CnPALs genes. Intra-species collinearity analysis revealed that all CnPALs were collinear with multiple PAL genes in C. nitidissima, while inter-species collinearity analysis indicated that CnPALs were collinear with the PAL genes in Camellia oleifera and Camellia sinensis. Furthermore, the transcriptomic data of C. nitidissima demonstrated tissue-specific expression of the CnPALs, although qRT-PCR validation showed some discrepancies with the sequencing result. The qRT-PCR revealed varied expression patterns among the six CnPALs, with the CnPAL1 gene showing relatively higher expression levels. Subsequently, cloning, prokaryotic expression, and enzyme activity analysis confirmed the effective catalytic activity of the CnPAL1 protein. Conclusions: This study lays the foundation for understanding the functions of CnPAL genes and offers insights for genetic improvement of C. nitidissima. Full article

This study aimed to conduct a first evaluation of maternal exposure to mycotoxins during pregnancy in Brazil through quantification of biomarkers in liver and serum samples from stillborn and neonates autopsied in the Clinical Hospital of Ribeirão Preto, state of São Paulo. Liver tissue (n = 43) and serum (n = 38) samples were collected from 43 patients and analyzed for biomarkers of aflatoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), zearalenone (ZEN), deoxynivalenol (DON), T-2 and HT-2 toxins by ultra-performance liquid chromatography coupled to tandem mass spectrometry. In total, 9 samples of liver (20.9%) and 33 serum (86.8%) had quantifiable levels of mycotoxins. In liver samples, aflatoxin M₁ (AFM₁) was quantified in two samples (median level: 0.38 ng/g), while four samples had OTA residues (median: 0.31 ng/g) and one contained ZEN (3.6 ng/g). Compared with liver tissue, serum samples had higher occurrence rates of mycotoxins, particularly AFM₁, OTA and ZEN. Nineteen serum samples (50%) contained 2–4 types of mycotoxins, indicating an effective transplacental transfer of major mycotoxins during pregnancy. Median levels of AFM₁, OTA, FB₁, ZEN, DON, T-2 and HT-2 toxins in serum samples were 0.48, 3.39, 30.6, 10.53, 5.71, 2.85 and 10.84 ng/mL, respectively. The most frequent cause of death was extreme prematurity (33% of cases), followed by preterm premature rupture of membranes (16% of cases) and morphological abnormalities (42% of cases). Results of this trial suggest potential associations between dietary mycotoxins and congenital anomalies. Further research should clarify the transplacental transfer of mycotoxins and their association with toxic effects during human prenatal development. Full article

In the regulatory market, it is not uncommon for ginseng radix et rhizoma (GR) to be adulterated with panacis quinquefolii radix (PR). Amid the digital transformation, this study puts forward a new method for the identification of GR adulterated with PR. Ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to detect multiple batches of GR and PR to obtain mass spectrometry data. The common ions were isolated from multiple batches of GR and PR, serving as GR and PR’s “ion matrices”. Furthermore, GR and PR’s “ion matrices” were used to eliminate intersecting ion data to extract the top-100 ions as GR and PR “matrix identity cards” (MICs). Then, GR and PR’s MICs were employed as a reference for identification, yielding contrast credibility (CC) as feedback. The results indicated that leveraging the MICs of GR and PR enables efficient and precise digital identification of the two herbs: pure GR showed CC ≥ 95% when matched with GR MIC (≤2% with PR MIC), pure PR showed CC ≥ 93% with PR MIC (≤3% with GR MIC), and non-parametric analysis confirmed significant differences between groups (p < 0.01). Even in 5% PR-adulterated samples, CC ranged from 24% to 28% (avg. 25.8%) when matched with PR MIC, leading to a 26% adulteration detection threshold. Moreover, two adulterated batches were identified among ten GR blind samples, which was consistent with verification via PR-specific pseudo-ginsenoside F₁₁. This research is practically valuable for distinguishing between GR and PR, combating adulteration, and reinforcing GR quality management. It also informs the digital identification of GR via UPLC-QTOF-MS and “MICs”, contributing to the digital quality control of traditional Chinese medicines (TCMs). Full article

This study was performed to investigate and compare the pharmacokinetic characteristics of tylvalosin tartrate in broiler chickens following oral administration of a nanocrystal suspension (PO-NM) or a soluble powder formulation (PO-SP), with intravenous administration (IV) of tylvalosin tartrate serving as the reference standard. A total of 30 healthy broiler chickens were randomly allocated into three groups (PO-NM, PO-SP, and IV; n = 10). Tylvalosin was administered at a dose of 25 mg/kg body weight (BW), and blood samples were collected at multiple time points from 0 to 24 h post-administration. Plasma concentrations of tylvalosin were quantified using a validated ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method, and pharmacokinetic parameters were calculated using non-compartmental analysis. The results showed no significant differences in the terminal elimination half-life (t_1/2λz) and mean residence time (MRT) between the two oral formulations. However, the time to maximum concentration (Tmax) of PO-NM (0.71 ± 0.09 h) was significantly shorter than that of PO-SP (1.42 ± 0.18 h) (p < 0.05), while the maximum plasma concentration (Cmax) of PO-NM (255.52 ± 111.88 ng/mL) was markedly higher than that of PO-SP (120.45 ± 45.82 ng/mL) (p < 0.05). Furthermore, the absolute bioavailability (F) of PO-NM (15.73 ± 4.29%) showed a modest increase compared with PO-SP (11.45 ± 4.66%); however, this difference did not reach statistical significance. Collectively, these findings demonstrate that the PO-NM formulation achieved faster absorption, higher peak plasma levels, and greater systemic exposure compared with PO-SP, without significantly altering the elimination process. Overall, nanoparticle formulation appears to enhance the oral pharmacokinetic performance of tylvalosin in broiler chickens, potentially reducing residue risks and offering substantial application value in poultry medicine. Full article

The fruits of Piper longum L. (long pepper), a spice and medicinal plant of the family Piperaceae, are widely used in South and Southeast Asian cuisine and traditional medicine, valued for their pungent flavor and aroma. The metabolomic profiling of P. longum using UPLC-qTOF-MS/MS provided a comprehensive chemical characterization of this traditional medicinal plant, revealing that lignans and amide alkaloids are the major classes of secondary metabolites. To further investigate its pharmacological potential, the bioactive ethyl acetate fraction was subjected to a SIRT1-targeted chemical investigation. This led to the isolation and structural elucidation of three previously undescribed compounds, a cadinene-type sesquiterpene (1) and two oxo-neolignan (2 and 5), along with four known compounds 3, 4, 6, and 7. Compounds (1–7) were evaluated for their ability to modulate p53-dependent transcriptional activity via SIRT1 activation using a luciferase reporter cell-based assay. SIRT1, a NAD⁺-dependent deacetylase, is a crucial regulator of longevity, metabolism, and cellular stress resistance, making it a key target for the treatment of age-related diseases. Compounds 2–7 exhibited significant SIRT1 activation, with compound 6 displaying particularly high efficacy, comparable to resveratrol, the most well-known natural SIRT1 activator. This study demonstrates that the discovery of novel chemical scaffolds through bioactivity-guided screening highlights the value of combining advanced metabolomics with pharmacological evaluation. The results support the traditional medicinal use of long pepper and its potential for development into functional foods or pharmaceuticals for healthy aging. Full article

Background: Shancigu is a traditional Chinese medicine which is effective at clearing heat, detoxifying, dissipating masses, and resolving nodules. It consists of the dried pseudobulbs of orchids such as Cremastra appendiculata, or Pleione yunnanensis. To deeply understand the differences in the compositional and pharmacological active compounds in Shancigu, this study employed widely targeted metabolomics to analyze differential metabolites between two Shancigu species, C. appendiculata and P. yunnanensis. Methods: In this study, ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to qualitatively, quantitatively, and differentially analyze the metabolites of C. appendiculata and P. yunnanensis. Results: Metabolite profiling identified 2890 compounds across 13 classes. Within these, 687 metabolites showed significant differential abundance (23.76% total), including 331 upregulated and 356 downregulated compounds. Pathway enrichment analysis revealed these differential metabolites primarily concentrated in stilbenoid biosynthesis (types I and II) and flavonoid aglycone biosynthesis. The most highly expressed metabolites in the Cremastra group were L-tyrosine, dopamine and 3,4-dihydroxybenzaldehyde-xylose-glucoside, while in the Pleione group, the most abundant metabolites were 3,5-dihydroxy-2’-methoxy-4-methylbibenzyl, Shancigusin F and aloifol I. C. appendiculata preferentially accumulates flavonoids and phenolic acids whereas P. yunnanensis favors terpenoid and nucleotide derivative production. Conclusions: This study identifies key differential metabolites in C. appendiculata and P. yunnanensis, providing basic data for the overall evaluation and breeding of Shancigu, laying a foundation for further quality control and precise medication of Shancigu. Full article

Heme metabolism is crucial for the function and longevity of legume nodules, with leghemoglobins (Lbs) serving as the primary heme sink and heme oxygenase (HO) mediating heme degradation. However, the precise functional relationship between HO and Lbs remains unclear. Here, we show that Lotus japonicus HO1 (LjHO1) is strongly induced in early-stage Lb-deficient nodules, but its expression gradually decreases during nodule development. Subcellular localization analysis revealed that LjHO1 is plastid-localized in uninfected cells of lb123 mutant nodules, consistent with its localization in wild-type nodules. Using CRISPR/Cas9, we generated a quadruple ho1lb123 mutant lacking LjHO1 and all three Lb isoforms in L. japonicus. Phenotypic analyses revealed that Lbs deficiency predominantly impairs nitrogen fixation, whereas loss of LjHO1 further reduces nodule formation. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis revealed that loss of Lbs strongly decreased heme accumulation, whereas LjHO1 deficiency slightly increased heme levels in nodules. These results demonstrate that Lbs are essential for heme accumulation and nitrogen fixation, while LjHO1 fine-tunes heme turnover, highlighting their complementary roles in maintaining nodule heme homeostasis and symbiotic efficiency. Full article

The Jurubatiba Sandbank National Park (PARNA Jurubatiba) is an ecological reserve characterized by harsh environmental conditions, including low rainfall, high sun exposure, and sandy soil. Among its native vegetation, Eremanthus crotonoides stands out for its richness in flavonoids, phenolic compounds, and sesquiterpene lactones. The objective of this study was to isolate and quantify sesquiterpene lactones from this species using ¹H NMR and to investigate their anti-SARS-CoV-2 potential and cytotoxicity against cancer cells. UPLC-(ESI)-MS/MS analyses enabled metabolite annotation, and semi-preparative HPLC-DAD allowed the isolation of centratherin and goyazensolide, which were identified by 1D and 2D NMR. In vitro assays showed that centratherin at 10 µM concentration reduced the viability of PC-3 and HCT-116 cancer cells by 100%, while goyazensolide had no noteworthy effects. Furthermore, enzymatic inhibition assays on SARS-CoV2 targets revealed that centratherin exhibited a lower apparent IC₅₀ of 12 µM against PL^pro, while goyazensolide was more active against 3CL^pro, with an IC₅₀ of 71 µM. Notably, the dichloromethane fraction demonstrated promising activity against both enzymes, with IC₅₀ values of 30 µM for PL^pro and 11 µM for 3CL^pro. This study reports, for the first time, the isolation of goyazensolide from E. crotonoides and highlights the potential of both sesquiterpene lactones as SARS-CoV-2 enzyme inhibitors. In contrast to centratherin, goyazensolide fortunately had almost no cytotoxic effects at inhibition concentration on the cells tested. This shows that anticancer and anti-SARS effects can be separated and should have different SARs, an important prerequisite for further development. Full article

Many central nervous system disorders (CNS), including chronic pain and migraine, involve metabolic changes in the brain. These changes are best detected and monitored in cerebrospinal fluid (CSF), which requires lumbar puncture. Blood-based measurements may offer an alternative, if they reflect CSF changes. To assess this, we measured and correlated the concentrations of 39 amino acids, biogenic amines, and other amines in blood and CSF of 95 healthy volunteers and, in addition, correlated the ratios of 741 amines. Amines were measured using a validated UPLC-MS platform. In healthy volunteers, only 4/39 (10.3%) analyzed amine metabolite concentrations had a correlation coefficient ≥ 0.70. Correlations of metabolite ratios were significantly better for 308/741 (41.5%) combinations. Specifically, ratios of amino acids showed high correlations. In addition, amines were investigated in 197 participants with migraine. Six amine metabolite ratios were different in migraineurs versus healthy volunteers. Most blood amine concentrations do not reflect those in CSF, but many of the ratios did correlate between CSF and plasma, showing diagnostic potential. This study improves our understanding of blood-CSF relationships, and our data suggest that ratios of amines may be of relevance to CNS disorders, as we showed for migraine. Full article

Background: Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited. Eupatorium lindleyanum DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear. Objective: This study aimed to evaluate the protective effects of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques. Results: SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL’s pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota–metabolite–inflammatory cytokine network, thereby maintaining gut–lung axis homeostasis and enhancing anti-inflammatory effects. Conclusions: SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut–lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI. Full article

Pharmaceuticals are emerging contaminants of global concern, but their occurrence and removal in semi-arid regions such as Algeria remain poorly documented. This study provides the first systematic evaluation of pharmaceutical and physicochemical parameters in two wastewater treatment plants (WWTPs) in Mascara: an activated sludge system (WWTP-1) and an aerated lagoon system (WWTP-2). Ten pharmaceuticals of different therapeutic classes were quantified using UPLC-HR-QTOF-MS in influent, effluent, and sludge samples, and removal efficiencies were compared using ANOVA and Principal Component Analysis (PCA). WWTP-1 showed higher efficiency, with >90% removal of COD, BOD₅, and ammonium, and near-complete elimination of sulfamethoxazole (99.9%) and atenolol (94%). In contrast, WWTP-2 achieved only moderate reductions (69% COD, 51% BOD₅) and low pharmaceutical removal, with negative efficiencies for persistent compounds such as carbamazepine, diclofenac, and ibuprofen. Weak correlations between macro- and micropollutants indicated that traditional indicators cannot predict pharmaceutical behavior. This work is the first to integrate physicochemical monitoring, pharmaceutical profiling, and multivariate analysis in Algerian WWTPs. The findings highlight the limitations of conventional treatment in semi-arid conditions and provide a critical baseline for adopting advanced technologies to mitigate pharmaceutical pollution in North Africa. Full article