{"title":"Orthogonal chemical-biological profiling of bioactive components from Olea europaea L. fruits for mitigating hypoxia-induced cellular injury","authors":"Chengfu Zhang , Jiangjuan Yuan , Xia Zhang , Wenjin Ma , Dong Pei , Lansheng Zhang , Lichun Zhao , Qingli Qu","doi":"10.1016/j.jpba.2025.117167","DOIUrl":"10.1016/j.jpba.2025.117167","url":null,"abstract":"<div><div>Hypoxic stress, a pathological hallmark of cardiovascular, oncological, and neurodegenerative diseases, underscores the need for safer hypoxia-targeting therapeutics beyond conventional agents with dose-limiting toxicities. The protective effect of polyphenols from <em>Olea europaea</em> L. fruit (<em>OEL</em>-F) against hypoxic injury in PC12 cells was investigated in this study. Furthermore, the main bioactive components responsible for this protective effect were isolated and characterized. An integrated chemometrics approach facilitated the systematic identification of 23 characteristic markers through HPLC analysis of 17 OEL-F extracts. Coupling with CoCl₂-induced hypoxia modelling in PC12 cells (cell viability assessed <em>via</em> MTT assay) and orthogonal biological validation to identify five hypoxia-alleviating bioactive markers precisely. S6 extract demonstrated significantly superior biological activity in the repair of hypoxic injury compared to all other groups (<em>p</em> < 0.01). Bioactivity-directed fractionation led to the identification of luteolin-4′-O-β-D-glucoside and oleuropein as primary bioactive constituents. Molecular docking analysis indicated that these compounds exhibit structural motifs analogous to vadadustat (a clinical PHD2 inhibitor), engaging residues His313/Tyr310 in the substrate pocket. Unlike vadadustat's Fe²⁺-chelating mechanism, these constituents act as potential competitive PHD2 inhibitors via non-chelating interactions at the catalytic site. Molecular docking suggests that <em>OEL</em>-F polyphenols may stabilize HIF-1α through PHD2 inhibition, proposing a novel natural product-driven strategy for safer hypoxia intervention.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117167"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220716","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}
Leo Wang , Chris Barton , Yan Wang , Nicole Sessler , Larry Wang
{"title":"A new deep field scan liquid chromatography–mass spectrometry method to identify host cell proteins in therapeutic proteins","authors":"Leo Wang , Chris Barton , Yan Wang , Nicole Sessler , Larry Wang","doi":"10.1016/j.jpba.2025.117164","DOIUrl":"10.1016/j.jpba.2025.117164","url":null,"abstract":"<div><div>Residual host cell proteins (HCPs) in therapeutic proteins pose a persistent challenge to detect due to their low abundance and wide dynamic range relative to the drug substance. To address this, we developed a “deep field scan” liquid chromatography tandem mass spectrometry (LC-MS/MS) method that enhances HCP detection without sample enrichment or clean-up, by leveraging an automated, cumulative target mass exclusion list and iterative data acquisition. Built on the Thermo Orbitrap AcquireX platform, this method optimizes MS efficiency by reducing redundant peptide sampling and improving MS/MS spectral quality, enabling higher-confidence HCP identification. Applying this method to NISTmAb demonstrated superior performance over traditional top10 data-dependent acquisition (DDA), confirming its viability as an alternative to native digest for monoclonal antibodies (mAbs). More importantly, its compatibility with non-antibody (non-mAb) biologics broadens its usage across diverse therapeutic modalities. Additionally, we established a benchmark HCP library from three additional commercial antibody standards, providing a valuable resource for cross-comparison within the HCP research community. By offering an automated and adaptable workflow, this method represents a novel and notable advancement in biologics impurity HCP characterization, supporting more efficient and comprehensive data collection for therapeutic protein development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117164"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199808","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}
Wenqu Yin , Haoyong Zou , Yujuan Xu , Qinyu Yu , Guizhi Song , Xiaolu Zhou , Zeqiong Yu , Kuanhong Xu , Zhi Zhang , Zhi Wang , Xilin Nie , Peng Geng
{"title":"Quantification of the percentage of lymphocyte-binding components in polyclonal anti-thymocyte/lymphocyte globulin products","authors":"Wenqu Yin , Haoyong Zou , Yujuan Xu , Qinyu Yu , Guizhi Song , Xiaolu Zhou , Zeqiong Yu , Kuanhong Xu , Zhi Zhang , Zhi Wang , Xilin Nie , Peng Geng","doi":"10.1016/j.jpba.2025.117165","DOIUrl":"10.1016/j.jpba.2025.117165","url":null,"abstract":"<div><div>The immunomodulatory and immunosuppressive properties of anti-thymocyte globulin (ATG)/anti-lymphocyte globulin (ALG) are primarily facilitated through the interaction between the lymphocyte-binding components of ATG/ALG (active ATG) and the antigens expressed on various immune cell populations. Nevertheless, the precise concentration and proportion of active ATG present in ATG/ALG preparations have yet to be definitively ascertained. In this study, we employed a methodology integrating flow cytometry and ELISA to quantify the percentage of active ATG in ATG/ALG preparations. The method was replicated six times to assess active ATG in ATG-Fresenius utilizing Jurkat cells, resulting in a coefficient of variation (CV) of 11.05 %. Analysis of 4 porcine immune plasma batches showed significant inter-batch variability in active ATG concentrations and total IgG concentrations. Analysis of 12 batches of porcine anti-thymocyte globulin (pATG) stock solutions revealed that the mean percentages and CV value for active ATG were 45.08 % and 23.58 %, respectively. Moreover, the biological activity assay demonstrated a strong correlation between the biological activity of pATG and the percentage of active ATG in the pATG preparation (r = 0.9283). In conclusions, we have developed an absolute quantification method for active ATG, which will facilitate precise pharmacokinetic analysis of active ATG and contribute to improving the potency testing and dosing regimens of ATG.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117165"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220806","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}
Yuanyuan Gu , Yue Wang , Guangyou Qu , Youfei Pen , Yiming Chen , Xiubo Zhu , Yuanyuan Li , Yang Wang , Fang Fang , Shuxiang Zhang , Fang Lu
{"title":"Xi Huang Pill exerts anti-triple-negative breast cancer effects by modulating gut microbiota, regulating glycerophospholipid metabolism, and promoting autophagy homeostasis","authors":"Yuanyuan Gu , Yue Wang , Guangyou Qu , Youfei Pen , Yiming Chen , Xiubo Zhu , Yuanyuan Li , Yang Wang , Fang Fang , Shuxiang Zhang , Fang Lu","doi":"10.1016/j.jpba.2025.117166","DOIUrl":"10.1016/j.jpba.2025.117166","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer, characterized by high malignancy and poor prognosis. Xihuang Pill (XHP), a traditional Chinese medicine (TCM) formulation, has demonstrated therapeutic efficacy against TNBC. This study investigates the antitumor mechanisms and therapeutic potential of XHP. The chemical composition of XHP was analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The murine TNBC model was established via orthotopic implantation of 4T1 cells, followed by XHP treatment. Multi-omics analyses including gut microbiota profiling, metabolomics, and molecular biology approaches were conducted, along with the use of a pseudo-germ-free mouse model.XHP inhibited TNBC cell proliferation, induced apoptosis, and suppressed tumor growth, while also enhancing immune function, as evidenced by an increased CD4 + /CD8 + T-cell ratio. Integrated analysis identified four key bacterial genera (Deferribacterota, Mucispirillum, Eisenbergiella, and Monoglobus) and 13 metabolites involved in glycerophospholipid metabolism. XHP downregulated PCYT1A and PCYT2, key enzymes in this pathway. However, antibiotic-induced depletion of gut microbiota abolished XHP’s antitumor and metabolic regulatory effects. Furthermore, XHP enhanced autophagy, as indicated by an increased LC3-II/I ratio and decreased p62 expression.In conclusion, XHP exerts antitumor effects against TNBC by modulating gut microbiota-dependent glycerophospholipid metabolism and restoring autophagy homeostasis. These findings provide novel insights into the anticancer mechanisms of TCM by elucidating microecological–metabolic interactions.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117166"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206675","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}
Yifan Bing , Xiaoling Ji , Fajing Qiang , Shuang Wu , Jiejing Sheng , Shuo Yang , Xiang Zou , Zhongyuan Qu
{"title":"Antidepressant efficacy and Q-markers determination of Dachaihu decoction: Combining pharmacology, correlation analysis, and network pharmacology approaches","authors":"Yifan Bing , Xiaoling Ji , Fajing Qiang , Shuang Wu , Jiejing Sheng , Shuo Yang , Xiang Zou , Zhongyuan Qu","doi":"10.1016/j.jpba.2025.117169","DOIUrl":"10.1016/j.jpba.2025.117169","url":null,"abstract":"<div><div>Dachaihu decoction (DCHT) was first recorded in the <em>Treatise on Febrile and Miscellaneous Diseases</em> and has the effects of reconciling shaoyang, reducing heat, and treating shaoyang minghe disease, vomiting, heart disease, depression and other diseases. DCHT is often used in the modern clinical treatment of digestive diseases, depression, and accompanying depression. However, despite its clinical application, pharmacodynamic studies of the antidepressant effects of DCHT have not been carried out, and the key pharmacodynamic substances involved have not been identified. The aim of this study was to confirm the antidepressant efficacy of DCHT, screen its quality markers (Q-markers), and establish a method for the determination of Q-markers of DCHT. The optimal extraction site of DCHT was determined <em>via</em> a reserpine-induced depressive zebrafish model, and further exploration of the pharmacological site was conducted in mice with liver depression and spleen deficiency-type depression (LDSD)<em>.</em> The antidepressant bioactive components of DCHT were identified via correlating ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC<img>Q<img>TOF<img>MS/MS) peak areas from 10 extraction sites with pharmacodynamic effects in zebrafish and further screened via reverse traceability of the core targets involved in the key pathways enriched by network pharmacology. Q-markers were subsequently determined through the antidepressant efficacy verification of potential pharmacologically active substances using a zebrafish depression model in conjunction with the principle of measurability, followed by content determination. The 95 % ethanol extract of DCHT was identified as the best antidepression extract. Among the 41 common components identified in the 10 extracts of different DCHT extraction sites, 10 potential antidepressant components were screened and verified to to have antidepressant effects. However, the extremely low contents of SSa and SSd make them difficult to measure, and the poor separation of Wogonin from adjacent peaks make the accurate determination of its content difficult. Therefore, on the basis of the principles of effectiveness and measurability, the remaining 7 ingredients, Baicalin, Wogonoside, Baicalein, Sinensetin, Skullcapflavone II, Oroxylin A, and SSb<sub>2</sub>, were defined as Q-markers for DCHT, and their total content was stable in the range of 0.7153∼0.7245 %. In conclusion, this study confirmed the antidepressant efficacy of DCHT and identified its antidepressant Q-marker, establishing the groundwork for further investigations into the antidepressant effect mechanism of DCHT and the creation of derivative products.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117169"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220717","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}
Tao Liu , Yiru Kong , Xiaoyu Ji , Chunguang Zheng , Chaoxin Zhou , Zhixin Li , Jin Xu , Qingcheng Guo , Ziqiao Sun , Xuekun Wang , Dapeng Zhang , Xinli Zhou , Hao Lin , Huaizu Guo
{"title":"Longitudinal profiling of cerebrospinal fluid N-glycome dynamics in glioblastoma patients treated with apatinib","authors":"Tao Liu , Yiru Kong , Xiaoyu Ji , Chunguang Zheng , Chaoxin Zhou , Zhixin Li , Jin Xu , Qingcheng Guo , Ziqiao Sun , Xuekun Wang , Dapeng Zhang , Xinli Zhou , Hao Lin , Huaizu Guo","doi":"10.1016/j.jpba.2025.117163","DOIUrl":"10.1016/j.jpba.2025.117163","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains a therapeutically intractable central nervous system malignancy with limited treatment options. Apatinib, a selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, shows emerging potential in recurrent or refractory glioblastoma, yet its impact on the cerebrospinal fluid (CSF) glycome remains unexplored. In this pioneering longitudinal study, we characterize the N-glycome dynamics in paired CSF specimens from GBM patients pre- and post-apatinib treatment using hydrophilic interaction-based ultra performance liquid chromatography (HILIC-UPLC)-fluorescence mass spectrometry-based glycan profiling. Our results highlight potential alterations in specific glycoforms, particularly an increase in GalNAcβ1–4GlcNAc (LacdiNAc or LDN), core fucosylation(a modification catalyzed by α1,6-fucosyltransferase (Fut8), which transfers L-fucose from GDP-fucose to the innermost GlcNAc residue), and bisecting glycans(a β1,4-linked GlcNAc attached to the core β-mannose residue), a decrease in sialylation and biantennary glycans among treatment responders. These shifts correlate with attenuated immunosuppressive signatures, suggesting enhanced immunomodulation that may contribute to apatinib’s therapeutic efficacy. This work uncovers the remodeling of the CSF glycome driven by apatinib, providing a novel molecular lens for understanding its anti-angiogenic/immune-modulating mechanisms and proposing CSF N-glycans as dynamic biomarkers for treatment efficacy in GBM.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117163"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213008","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}
Xianyin Zhang , Xiangping Liu , Jie Xu , Wenfang Sun , Xin Xu , Wenliang Ji
{"title":"Simultaneous determination of 11 organophosphorus flame retardants and 6 metabolites in human urine by ultra-performance liquid chromatography tandem mass spectrometry","authors":"Xianyin Zhang , Xiangping Liu , Jie Xu , Wenfang Sun , Xin Xu , Wenliang Ji","doi":"10.1016/j.jpba.2025.117162","DOIUrl":"10.1016/j.jpba.2025.117162","url":null,"abstract":"<div><div>Organophosphorus flame retardants (OPFRs) are widely used chemicals with significant health risks to humans. OPFRs are metabolized and excreted primarily through urine, making urine a key matrix for assessing human exposure levels. Therefore, this study developed a method combining the Quick, Easy, Cheap, Effective, Rugged, Safe (QuEChERS) approach with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 11 OPFRs and 6 organophosphorus flame retardant metabolites (mOPFRs) in human urine. All target compounds exhibited excellent linearity, with correlation coefficients (<em>r</em>²) exceeding 0.9988. The limits of detection (LODs) and the limits of quantification (LOQs) ranged from 0.01 ng/mL to 0.05 ng/mL and 0.03 ng/mL to 0.16 ng/mL, respectively. Except for tricresyl phosphate (<50 %), the spiked recoveries for the other target compounds were 51.4–117 %, 52.4–100 %, 63.9–128 %, and 89.0–112 % at four concentration levels. All analytes showed intra-day and inter-day precision with relative standard deviations (<em>RSDs</em>) of 0.8–18.8 % and 1.4–12.2 %, respectively. Analysis of children’s urine revealed distinct metabolic patterns: triphenyl phosphate and tris(1,3-dichloro-2-propyl) phosphate were not detected, while their metabolites, diphenyl phosphate and bis(1,3-dichloro-2-propyl) phosphate, were found in the urine. In contrast, tris(2-butoxyethyl) phosphate, tributyl phosphate, tri(2-chloroethyl) phosphate, and tris(1-chloro-2-propyl) phosphate suggested possible co-occurrence of parent compounds and metabolites. The developed method is simple, sensitive and robust, and has the advantage of high throughput for screening 17 targets including parent compounds and metabolites. These features make it suitable for assessing the exposure risk of OPFRs in urine.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117162"},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220715","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":"Impact of Tribulus terrestris supplementation on urinary steroid profiles: A short term pilot study","authors":"Lavinia Minotti , Emilia Marchei , Mariangela Biava , Adele Minutillo , Francesco Paolo Busardò , Simona Pichini , Giulia Bambagiotti","doi":"10.1016/j.jpba.2025.117160","DOIUrl":"10.1016/j.jpba.2025.117160","url":null,"abstract":"<div><div>Steroid metabolism is a complex biochemical process susceptible to modulation by exogenous compounds. Tribulus terrestris (TT) is a widely used herbal supplement marketed for its purported ergogenic and anabolic effects. This preliminary investigation aimed to assess the impact of short-term TT supplementation on urinary steroid profiles. Urine samples were obtained over a two-month period from eight male and seven female recreational athletes declaring to daily consume a TT extract. 5α-androstane-3α,17β-diol, 5β-androstane-3α,17β-diol, androsterone, etiocholanolone, 11β-hydroxyandrosterone, 11β-hydroxyetiocholanolone, dihidrotestosterone, 5alpha-Androstane-3,17-dione, epitestosterone, testosterone, 4-androstene-3,17-dione concentrations, along with metabolic ratios, were quantified using a validated gas chromatography–tandem mass spectrometry (GC–MS/MS) methodology. In male recreational athletes, time-dependent increases in 4-androstene-3,17-dione, epitestosterone and testosterone were observed; however, no statistically significant differences were detected between urine samples collected before and during TT extract supplementation. In female participants, an initial increase followed by a subsequent decrease in all measured steroid profile markers was detected, but similarly to the male cohort, no statistically significant differences were identified between samples collected before and during TT supplementation. Despite considerable inter-individual variability in urinary steroid concentrations, no statistically significant alterations in steroid profiles and ratios were observed pre-versus post-supplementation. Although derived from a small sample size, these pilot data suggest that short–term TT supplementation does not elicit measurable changes in urinary steroid hormone profiles under the conditions of this study and is unlikely to interfere with endogenous steroid hormones turnover. Consequently, these findings raise questions the efficacy of TT as a performance-enhancing agent and underscore the necessity for further mechanistic studies on a broader cohort of TT consumers for a larger period of time.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117160"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155342","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}
Francesca Romana Mammone , Simone Manetto , Giulia Mazzoccanti , Daniele Sadutto , Marco Pierini , Roberto Cirilli
{"title":"Determination of enantiomerization barriers of desloratadine and its N-oxide derivative by dynamic enantioselective high-performance liquid chromatography and off-column racemization experiments","authors":"Francesca Romana Mammone , Simone Manetto , Giulia Mazzoccanti , Daniele Sadutto , Marco Pierini , Roberto Cirilli","doi":"10.1016/j.jpba.2025.117159","DOIUrl":"10.1016/j.jpba.2025.117159","url":null,"abstract":"<div><div>Desloratadine, a tricyclic histamine H<sub>1</sub>-receptor antagonist, is employed in the treatment of asthma and other allergic conditions. Its efficacy against various types of tumors has also been demonstrated. The molecule possesses a non-planar central seven-membered ring, devoid of a plane of symmetry, which confers planar stereogenicity. In this study, the energy barriers for the inversion of the p<em>R</em> and p<em>S</em> enantiomers, which occurs via a near-planar transition state, have been determined by on-column dynamic high-performance liquid chromatography and parallel kinetic off-column experiments based on electronic circular dichroism measurements. The kinetic and thermodynamic data pertinent to enantiomerization process were compared with those obtained for the N-oxide derivative of desloratadine. The results indicated that the targeted oxidation increased the activation enantiomerization barriers, thus conferring configurational stability to enantiomers. To complete the work, the absolute configuration of the enantiomers of the N-oxide derivative of desloratadine was established by comparing their experimental and theoretical chiroptical properties.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117159"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155343","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}
Jingyi Song , Yuan Xu , Jihong Liu , Yuqing Zhong , Ying Hong , Shiqi Liu , Xiaojun Gou , Yan Wu , Quanfang Jin
{"title":"Bushen Huoxue formula attenuates recurrent spontaneous abortion by modulating arginine metabolism and macrophage polarization at the maternal-fetal interface","authors":"Jingyi Song , Yuan Xu , Jihong Liu , Yuqing Zhong , Ying Hong , Shiqi Liu , Xiaojun Gou , Yan Wu , Quanfang Jin","doi":"10.1016/j.jpba.2025.117161","DOIUrl":"10.1016/j.jpba.2025.117161","url":null,"abstract":"<div><div>The aim of this study was to clarify the effects of BSHXF on pregnancy outcome and macrophage polarization at the maternal-fetal interface in a mouse model of recurrent spontaneous abortion (RSA). The RSA model was established using the CBA/J × DBA/2 mating method. Network pharmacology predicted the mechanism of BSHXF intervention in RSA and verified by Western blotting. Immunofluorescence and RT-qPCR were used to measure the levels of macrophage-associated cytokines at the maternal-fetal interface. Placental metabolomics was used to analyze the mechanism of macrophage regulation by BSHXF and verified by ELISA. BSHXF improved embryonic resorption and hormone levels in RSA mice and restored abnormal NF-κB signaling, which was achieved in part by modulating macrophage polarisation status. BSHXF intervention decreased M1 macrophage polarization while elevating M2 macrophage levels. Metabolomics indicated that decreased inducible nitric oxide synthase (iNOS) pathway and elevated arginase-1 pathway (Arg-1) pathway in the placenta were the key mechanisms of macrophage polarization. This study provides innovative insights into the mechanism by which BSHXF ameliorates RSA in mice, providing a scientific basis for further pharmacological research.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"267 ","pages":"Article 117161"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199803","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}