Journal of Chromatography B最新文献

{"title":"A sensitive method for confirming the clearance of caffeine and its three primary metabolites in sheep tissues destined for human consumption","authors":"Gregory S. Doran ,&nbsp;Susan M. Robertson ,&nbsp;Michael A. Friend ,&nbsp;Scott H. Edwards","doi":"10.1016/j.jchromb.2026.124912","DOIUrl":"10.1016/j.jchromb.2026.124912","url":null,"abstract":"<div><div>Caffeine is a naturally occurring stimulant that is consumed in coffee, tea, and energy and soft drinks, but may also be used therapeutically in humans and animals. Caffeine initially degrades rapidly via demethylation to theobromine, paraxanthine and theophylline, prior to further degradation to other metabolites. A method was developed to separate and quantify the four chemicals, which is generally complicated by co-elution of paraxanthine and theophylline, which are the two bioactive metabolites. Processes to extract and purify the four analytes from liver, kidney, muscle, brain, perirenal and abdominal fats, plasma and milk were also developed and provided limits of quantitation as low as 1 ng/g in solid tissues and 1 ng/mL in milk and plasma using a combination of solvent and solid phase extractions. Sample homogenisation considerations and recovery at different stages was investigated to identify the areas of greatest analyte loss. A study was conducted involving the daily oral caffeine dosing of pregnant merino ewes at a rate of 25 mg/kg for 52 days until the birth of lambs. Tissue samples and milk were collected from ewes and lambs up to 28 days after birth and analysed using the new methodologies. Caffeine and the three primary metabolites appeared in all tissues analysed at high concentrations at day 0 (birthing), but declined by 99.9 % in all tissues in ewes by day 7, and all tissues except plasma (98.5 %) in lambs by day 7. All analytes were only detected in milk from ewes at day 0, but provided a source of caffeine and its metabolites to suckling newborn lambs, which may be responsible for the slower clearance from lamb plasma. Theophylline was the dominant metabolite in both ewes and lambs, followed by paraxanthine, while theobromine was only detected at much lower concentrations. The results derived from this animal study using this new method indicate that accumulation of caffeine and its three primary metabolites does not occur in the milk or tissues of ewes or lambs.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124912"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Removal of aspirin and tetracycline hydrochloride using UiO66/Polydopamine/bacterial cellulose composite: Phenomenological modeling and theoretical study","authors":"Nadia Bouaziz ,&nbsp;Fatma Aouaini ,&nbsp;Abdelmottaleb Ben Lamine","doi":"10.1016/j.jchromb.2025.124910","DOIUrl":"10.1016/j.jchromb.2025.124910","url":null,"abstract":"<div><div>The effective removal of antibiotics and non-steroidal anti-inflammatory drugs and their combined pollutants is critical for both the aquatic environment and human health. This study evaluates the removal of pharmaceutical waste through the adsorption of aspirin and tetracycline hydrochloride (TC) onto the surface of a UiO-66/Polydopamine/Bacterial Cellulose composite (UiO-66/PDA/BC). Both theoretical and experimental approaches were considered to investigate the removal of aspirin and TC. The theoretical study, based on statistical physics theory, employs three analytical models to describe the adsorption phenomena of these drugs at the molecular level. According to the fitting results, the adsorption of both drugs onto the UiO-66/PDA/BC composite is an endothermic process and follows a monolayer adsorption mechanism with one type of site. Regarding the number of adsorbed molecules per site (n), the analysis indicates that both multi-docking (<em>n</em> &lt; 1) and multi-molecular (<em>n</em> &gt; 1) adsorption mechanisms are possible for aspirin and TC on UiO-66/PDA/BC. The adsorption capacities at saturation of the UiO-66/PDA/BC adsorbent deduced by the monolayer model are found to be 147.34–215.05 mg/g for aspirin and 193.72–246.66 mg/g for TC. Furthermore, adsorption energy calculations suggest that the removal of these pharmaceutical pollutants occurs primarily through physical interactions. The thermodynamic analysis confirms the spontaneous and feasible nature of the adsorption of both drugs onto the UiO-66/PDA/BC composite.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124910"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and application of SPE-UHPLC-MS/MS methods for quantification of 29 steroids in rat serum","authors":"Haiyang Cui ,&nbsp;Dongliang Yang ,&nbsp;Yonggang Zheng ,&nbsp;Jing Li ,&nbsp;Hairui Yan ,&nbsp;Xiaoli Gao","doi":"10.1016/j.jchromb.2026.124924","DOIUrl":"10.1016/j.jchromb.2026.124924","url":null,"abstract":"<div><div>Steroids and their metabolites play crucial roles in reproductive health, endocrine diseases, and tumor development. Comprehensive analysis of these compounds is essential for both mechanistic investigations and clinical evaluations. Although comprehensive analytical methods have been established for steroids in human clinical samples, their direct application to rat specimens remains limited, particularly with the absence of validated methods for detecting certain hydroxylated steroid metabolites in vivo. This study developed highly sensitive solid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry methods for the quantitative analysis of 29 steroid metabolites. Through optimized derivatization of steroids and integration of two-dimensional liquid chromatography techniques, the method effectively reduces interference from non-volatile salts and overcomes trace-level detection challenges. Method validation demonstrated a wide linear range (0.002–250 ng/mL), low limits of quantification (2–100 pg/mL), high accuracy (88–114%), and precision (intra- and inter-batch CV ≤14%). The method exhibited acceptable extraction recovery, matrix effects, and stability, confirming compliance with regulatory standards. The validated method was successfully applied to characterize serum steroid metabolic profiles in both <em>N</em>-methyl-N-nitrosourea-induced breast cancer and ovariectomized rat models, revealing alterations in estrogen 2-hydroxylation and pregnenolone 21-hydroxylation pathways mediated by key steroidogenic enzymes, including CYP1A1/CYP1B1 and potentially CYP21A2-independent mechanisms, providing robust support for preclinical research on steroid-related diseases.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124924"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Portable mass spectrometry systems for point-of-care testing: technologies, applications, and clinical implementation","authors":"Brooks B. Pond,&nbsp;Madison Hoskins,&nbsp;Haylie Hollis,&nbsp;Stacy Brown","doi":"10.1016/j.jchromb.2026.124923","DOIUrl":"10.1016/j.jchromb.2026.124923","url":null,"abstract":"<div><div>Portable mass spectrometry systems have shown great potential in point-of-care testing and field-based diagnostics, as they fill important gaps in decentralized clinical analysis. Conventional centralized laboratory testing may delay clinical decision making due to transport and analysis times. For conditions where transportation is limited, these delays disproportionately affect resource-poor settings. Advances in technology allow the design and assembly of lightweight, portable MS systems. Fundamental issues such as size reduction, power consumption, and vacuum requirements have been addressed as the MS miniaturization field has developed. These advances have generated commercially available devices and home-built instruments capable of rapid analysis, often without extensive sample preparation. Studies on applicability of portable MS have already shown utility in multiple fronts, such as therapeutic drug monitoring for HIV, psychiatric drugs, and cardiac interventions; drug profiling in forensic medicine; disease diagnosis including malaria detection; and cancer tissue analysis. Nevertheless, the tradeoff between miniaturization and sensitivity, small mass resolution relative to benchtop instruments, and challenges in reproducibility represent ongoing issues with miniaturized mass spectrometry. Despite these disadvantages, significant clinical potential can be concluded from current published evidence. With the development of complementary sample preparation methods and miniaturization technology, portable MS systems could see implementation in emergency departments, mobile clinics, and resource scarce clinic environments.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124923"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous determination of short-chain fatty acids and tryptophan metabolites by a propyl chloroformate- derivatized GC–MS approach","authors":"Yefeng Han ,&nbsp;Xiaofang He ,&nbsp;Yueling Gong ,&nbsp;Mingxiao Li ,&nbsp;Lili Sheng ,&nbsp;Ningning Zheng ,&nbsp;Jianbo Wan ,&nbsp;Houkai Li ,&nbsp;Yuanyuan Li","doi":"10.1016/j.jchromb.2026.124925","DOIUrl":"10.1016/j.jchromb.2026.124925","url":null,"abstract":"<div><div>Short-chain fatty acids (SCFAs) and tryptophan metabolites, serve as key mediators of host-microbiota crosstalk, influencing physiological and pathological processes. Their interconnected roles necessitate simultaneous quantification to fully elucidate the potential mechanism of gut microbiota in metabolic diseases. However, they are difficult to be detected simultaneously due to differences in content or different polarity which contain specific carboxylic group, amino group or phenolic hydroxyl groups. In current study, our primary goal is to establish a rapid and sensitive quantitative measurement for SCFAs and tryptophan metabolites by using propyl chloroformate-(PCF) derivatization based on gas chromatography-triple quadrupole mass spectrometry (GC–MS/MS) analysis. Then, we applied the established method in measurement of serum samples from healthy subjects and metabolic associated fatty liver disease (MAFLD) patients. First, we optimized the reaction conditions including PCF volume, reaction time, extraction reagent ratio, and alkaline reagent concentration, enabling the simultaneous detection of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, 2-methylvaleric acid, hexanoic acid, indole, succinic acid, quinolinic acid, indole acetic acid, glutamine, indole butyric acid, 3-hydroxyanthranilic acid, melatonin, kynurenine, tyrosine, and tryptophan. 2-chloro-<em>L</em>-phenylalanine was set as the internal standard. The optimized condition showed good linearity, and the intra/inter-day precision achieved in the range from 0.81% to 14.88%. The recovery ranged from 85.68% to 114.50% and the matrix effect ranged from 85.81% to 113.42%. In addition, the influence of different storage conditions on sample stability was also acceptable. Finally, the quantitation result of serum samples indicated that isovaleric acid, quinolineic acid, indoleacetic acid, glutamine, melatonin, tyrosine, and tryptophan had significant difference between healthy subjects and MAFLD patients. The levels of isovaleric acid, indoleacetic acid, glutamine, tyrosine, and tryptophan had significant correlations with clinical indicators such as ALT, AST, Cap, Cr and TG, supporting their potential for further translational studies. In summary, this improved method is applicable for quantitative measurement of SCFAs and tryptophan metabolites, as well as those endogenous metabolites containing carboxylic, amino and phenolic hydroxyl groups.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124925"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Library-assisted UHPLC-Q-TOF-MS/MS bioanalytical profiling of Qiling Hushen granules: In-vivo metabolic mapping and kidney-biased distribution","authors":"Pei Sheng ,&nbsp;Mingjin Zhang ,&nbsp;Shuqi Wang ,&nbsp;Shuyi Peng ,&nbsp;Jiakun Li ,&nbsp;Yi Liu ,&nbsp;Kaixuan Xu ,&nbsp;Xiaofei An","doi":"10.1016/j.jchromb.2026.124913","DOIUrl":"10.1016/j.jchromb.2026.124913","url":null,"abstract":"<div><div>Qiling Hushen Granules (QLHSG), a multi-herb prescription widely used for diabetic kidney disease (DKD), lacks system-level evidence linking chemical features with <em>in-vivo</em> disposition. A library-assisted UHPLC–Q-TOF-MS/MS workflow was developed to integrate <em>in-vitro</em> phytochemical profiling with <em>in-vivo</em> prototype/metabolite elucidation and organ-level biodistribution. An in-house spectral library was constructed using reference standards, open databases and diagnostic-ion rules, enabling high-confidence annotation based on retention time, accurate mass and MS/MS fragmentation. In total, 166 <em>in-vitro</em> constituents were cataloged. <em>In vivo</em>, 78 prototype constituents were characterized. Metabolites were assigned by matrix (bile 46, feces 44, plasma 27, urine 156), delineating phase I/II biotransformation and elimination routes. Tissue mapping demonstrated kidney-biased accumulation of multiple prototypes and metabolites, indicating that renal targeting is consistent with the therapeutic context. Dominant exposure classes included iridoids and flavonoids. Representative bioactives were astragaloside IV, calycosin, paeoniflorin, secologanoside and sweroside. Network analysis combined with molecular docking connected absorbed constituents to DKD-relevant targets (<em>e.g.</em>, TP53, EGFR, AKT1, STAT3, HIF1α), providing plausible mechanistic insights. Overall, this workflow establishes a reproducible pathway, from chemical profiling to systemic exposure and organ targeting in complex herbal formulations. For the first time, it provides system-level chemical evidence supporting the renoprotective effects of QLHSG.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124913"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward needle-free lamotrigine monitoring: Proof-of-concept for saliva and dried saliva spot analysis by LC-MS/MS - a short communication","authors":"Viktória Ďurčová ,&nbsp;Marta Pelcová ,&nbsp;Pavel Šmak ,&nbsp;Ondřej Strýček ,&nbsp;Jana Gregorová ,&nbsp;Ondřej Peš ,&nbsp;Zdeněk Glatz ,&nbsp;Pavel Šištík ,&nbsp;Jan Juřica","doi":"10.1016/j.jchromb.2026.124929","DOIUrl":"10.1016/j.jchromb.2026.124929","url":null,"abstract":"<div><div>Recent advancements in micro-sampling methods provide non-invasive options for collecting biological samples used in therapeutic drug monitoring (TDM). Lately, alternative matrices such as capillary blood and saliva/oral fluid in the form of dried saliva spots, have attracted considerable interest. These matrices represent a promising approach for TDM, as they could improve accessibility while preserving analytical precision.</div><div>The study developed and validated an LC-MS method for lamotrigine quantitation in saliva and Dried Saliva Spots (DSS). Samples were prepared via protein precipitation (methanol: acetonitrile: water, 7:2:1) and dilution, followed by separation on a Luna Omega C18 Polar column and detection in ESI+ mode. An isotopically labelled internal standard was employed, ensuring compliance with EMA guidelines. The linearity was demonstrated for lamotrigine concentrations ranging from 0.20 to 25 mg/L in both dried saliva spot and saliva samples.</div><div>Saliva and DSS samples from patients were used to compare lamotrigine concentrations with plasma levels determined by a hospital-accredited laboratory. Findings demonstrated a strong correlation between evaluated matrices and plasma (<em>R</em> = 0.847 for saliva and plasma, and <em>R</em> = 0.839 for DSS and plasma, both <em>p</em> &lt; 0.0001), underscoring the promise of saliva and DSS as substitutes for TDM. This technique improves patient comfort and accessibility through a non-invasive sampling method while ensuring accuracy.</div><div>These findings provide a foundation for broader clinical implementation of alternative-matrix TDM, representing a significant step toward patient-centred, accessible pharmacotherapy and enabling improved LTG monitoring in ambulatory and remote settings.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124929"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying a vacuum ultraviolet detector for liquid chromatography: Simultaneous analysis of four organic acids and four carbohydrates in a fermentation process","authors":"Mayur Bansal ,&nbsp;Annika Dombrowski ,&nbsp;Chinoso Nwanebi ,&nbsp;Dale Harrison ,&nbsp;Hal S. Alper","doi":"10.1016/j.jchromb.2026.124921","DOIUrl":"10.1016/j.jchromb.2026.124921","url":null,"abstract":"<div><div>The initial application of a prototype vacuum ultraviolet (VUV) absorption detector system for high performance liquid chromatography (HPLC) was validated and characterized. This detector enabled simultaneous detection and quantification of four organic acids—lactic, acetic, itaconic, and citric along with four carbohydrates—glucose, fructose, galactose, and lactose. This collection of analytes was selected based on their prevalence in fermentations, metabolic production interest, and occurrence in food processes/chemistry. Full spectrum VUV data, collected across 7 discrete wavelength bands centered at 177.3, 190.3, 203.1, 215.8, 228.3, 240.7, and 252.9 nm, yielded unique fingerprints that allowed for separation and quantification of strongly co-eluting peaks, most notably the hexose sugars. Separations were performed on an Aminex HPX-87H ion exclusion column using 5 mM H₂SO₄ as the isocratic mobile phase at 0.6 mL/min, with samples preheated to 40 °C. Across the eight analytes, Hydra limits of detection spanned 0.0228–3.59 g/L, with calibration linearity of R² = 0.941–0.998. The VUV prototype maintained linear response up to 100 g/L for all analytes (60 g/L for itaconic acid), whereas refractive index detection saturated between ∼10–60 g/L depending on the analyte. Spectral deconvolution recovered co-eluting organic acids with ∼1–4% error and the co-eluting hexose cluster within ∼11–19% error, demonstrating practical spectral selectivity for overlapped peaks. This extended dynamic range can eliminate the need for sample dilution thus greatly streamlining workflow processes and minimizing the dilution of trace components. The combination of quantitative accuracy and spectral selectivity was demonstrated though the monitoring of glucose utilization and lactic acid production during a seven-day <em>Saccharomyces cerevisiae</em> fermentation with minimal sample preparation. These results support the potential of LC-VUV detection as a robust, high-throughput method for metabolite analysis in high titer bioprocessing applications. However, a current limitation of the prototype is reduced sensitivity at low concentrations relative to conventional detectors, indicating that present performance is best suited to higher titer samples.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124921"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simple ion-pairing reversed phase LC-UV method for the relative quantification of capping species in mRNA-based modalities","authors":"Jonathan Maurer ,&nbsp;Denis Bouchard ,&nbsp;Agathe Bousquier ,&nbsp;Camille Malburet ,&nbsp;Jean-François Cotte ,&nbsp;Davy Guillarme","doi":"10.1016/j.jchromb.2026.124922","DOIUrl":"10.1016/j.jchromb.2026.124922","url":null,"abstract":"<div><div>Messenger RNA (mRNA)-based therapeutics and vaccines rely on proper 5′ capping to ensure translational efficiency, stability, and reduced reactogenicity. Current analytical approaches for capping evaluation often rely on mass spectrometry (MS) and fluorinated solvents, which are costly, technically demanding, and not always suitable for quality control (QC) laboratories. Here, we describe the development of a simple, robust, and QC-compatible ion-pairing reversed-phase liquid chromatography method coupled with UV detection (IP-RPLC-UV) for the relative quantification of key 5′ capping species in mRNA modalities, including uncapped, Cap 0, Cap 1, and Cap G transcripts, as well as non-templated additions (+G). The method employs targeted cleavage of the 5′ end using an oligo hybridization and RNase H digestion strategy, enabling baseline resolution of capping species within 20 min. A systematic screening of various ion-pairing reagents demonstrated that butylammonium acetate offered the optimal balance between retention and resolution, while a design of experiments approach identified critical parameters influencing performance and ensured method robustness. Method sensitivity was confirmed with a lower limit of quantification at 0.01 mg/mL for uncapped species, and repeatability testing showed consistent results across samples. This study introduces the first IP-RPLC-UV method tailored for routine relative quantification of cap structures, providing a practical alternative to MS-based workflows and facilitating the implementation of accessible, reliable analytical control strategies for mRNA drug development.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1271 ","pages":"Article 124922"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bupleurum polysaccharide improves CUMS-induced depressive behavior in rats by regulating the “microbiota-gut-brain Axis”: a mechanism study based on metabolomics and metagenomics","authors":"Hongcai Zhang,&nbsp;Shuxiang Zhang ,&nbsp;Xuan Li,&nbsp;Wenran Wang,&nbsp;Haixue Kuang","doi":"10.1016/j.jchromb.2025.124905","DOIUrl":"10.1016/j.jchromb.2025.124905","url":null,"abstract":"<div><div>This study aimed to comprehensively investigate the antidepressant mechanisms of Bupleurum polysaccharide (BP) through the microbiota-gut-brain axis, employing an integrated multi-omics approach. Using a chronic unpredictable mild stress (CUMS) rat model of depression, we evaluated BP's effects on depressive-like behaviors and analyzed its regulatory mechanisms on metabolites and gut microbiota through combined metabolomics and metagenomics. Structural characterization revealed that Bupleurum polysaccharide SPAP-1 is an acidic homogeneous polysaccharide with a molecular weight of approximately 100 kDa, primarily composed of glucose, mannose, rhamnose, and other monosaccharides. Pharmacodynamic assessments demonstrated that BP significantly ameliorated CUMS-induced depressive behaviors, including weight loss, reduced food intake, anhedonia, and behavioral despair (<em>P</em> &lt; 0.05). Metabolomic analysis identified 19 differential metabolites, with BP reversing 11 of them, primarily involved in phenylalanine and tryptophan metabolism pathways. Western blot analysis confirmed BP's regulatory effects on key enzymes Got1 and Lta4h. Metagenomic results showed that BP remarkably reshaped gut microbiota structure, restored microbial diversity, optimized the Firmicutes/Bacteroidetes ratio, enriched beneficial genera (Agathobacter, Phocaeicola), and inhibited pathogenic genera (Ruminococcus). Crucially, integrated multi-omics analysis revealed significant microbiota-metabolite correlations, demonstrating that BP-promoted beneficial bacteria positively correlated with neurotransmitter precursors, while BP-inhibited pathogenic bacteria associated with pro-inflammatory mediators. Mediation analysis further established the “microbiota → metabolite → behavior” causal chain, with Ruminococcus → LTB4 → despair behavior accounting for 42.3 % of the mediation effect. In conclusion, Bupleurum polysaccharide ameliorates depressive-like behaviors through multi-target regulation of the metabolite-microbiota interaction network, highlighting its potential as an antidepressant agent or functional food and providing a novel research paradigm for understanding the multi-target characteristics of traditional Chinese medicine polysaccharides.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1270 ","pages":"Article 124905"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}