Journal of pharmaceutical and biomedical analysis最新文献

{"title":"State-of-the-art chromatographic and mass spectrometric techniques in heparin structural analysis.","authors":"Yilan Ouyang, Siqi Yang, Wei Wang, Jianzhou Cui, Zhenqing Zhang","doi":"10.1016/j.jpba.2024.116625","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116625","url":null,"abstract":"<p><p>Heparin is the most extensively used anticoagulant in clinical practice. It is a highly sulfated, linear polysaccharide composed of repeating disaccharide units. As a member of the glycosaminoglycan (GAG) family, heparin's complex structure features significant molecular weight variability, diverse sugar residues, and variable sulfation patterns. Low molecular weight heparins (LMWHs), produced through chemical or enzymatic depolymerization, are distinguished by their reduced molecular weight and offer therapeutic advantages, including lower bleeding risks, reduced immunogenicity, and higher bioavailability following subcutaneous administration. The structural intricacy of heparin-based drugs presents major challenges for quality control, clinical safety, process optimization, and therapeutic expansion. Advanced analytical methods, particularly LC and MS, remain at the forefront of efforts to elucidate the detailed structures of these drugs. This review highlights recent progress in chromatographic and MS-based analysis techniques for heparin and its derivatives, including the application of computational algorithms for structural elucidation. The focus is on the analytical methodologies, their innovations, and limitations, while also exploring how machine learning and bioinformatics tools are shaping the future of heparin quality control and therapeutic application. This comprehensive review provides a reference point for researchers engaged in the structural analysis of heparin-based drugs and offers insights into the future development of novel analytical strategies for improving the safety and efficacy of these critical anticoagulants.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116625"},"PeriodicalIF":3.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822286","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 validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous analysis of isoniazid and pyrazinamide in cerebrospinal fluid.","authors":"Sydwell Poulo Maputla, Anton Joubert, Sandra Castel, Marthinus van der Merwe, Edda Zangenberg, Sean Wasserman, Kelly E Dooley, Lubbe Wiesner","doi":"10.1016/j.jpba.2024.116613","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116613","url":null,"abstract":"<p><p>For the effective treatment of tuberculosis with first-line anti-tubercular drugs, drug concentrations need to be measured at the site of infection to determine drug exposure. To enable the measurement of the anti-tuberculosis drugs isoniazid and pyrazinamide in the nervous system of patients with tuberculous meningitis, an analytical method was developed and validated for the quantification of these drugs in human cerebrospinal fluid. Samples were prepared by solid phase extraction using Strata-X polymeric extraction plates. The analytes were separated by high-performance liquid chromatography on an Atlantis T3, 100 A, 3 µm, 2.1 mm × 100 mm analytical column with gradient elution, employing a mobile phase that consisted of acetonitrile-methanol-formic acid (50:50:0.1, v/v/v), at a flowrate of 0.25 mL/min. The total run time was 4.5 minutes, and the average retention times of isoniazid and pyrazinamide were 1.1 and 1.3 min, respectively. The analytes and their respective deuterated internal standards were detected on a Sciex API4000 triple quadrupole mass spectrometer applying positive electrospray ionization with multiple reaction monitoring as the detection mode. The method was validated according to the FDA and EMA guidelines. The method was demonstrated to be accurate, reproducible, and robust, showing the necessary sensitivity and specificity for the quantification of isoniazid and pyrazinamide in cerebrospinal fluid. The method was successfully applied to analyze clinical samples from the LASER-TBM and TBM-KIDS clinical studies.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116613"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801183","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":"Integrated untargeted metabolomics and bioactivity studies as new insights into the chemotaxonomy of Hura crepitans specimens from Peru and Sub-Saharan Africa.","authors":"Elise Crossay, Valérie Cristofoli, Pedro Vásquez-Ocmín, Gabriel Vargas-Arana, Hospice Dassou, Arthur-Joel Semedo, Mamoudou Alao, Guillaume Marti, Nicolas Fabre","doi":"10.1016/j.jpba.2024.116583","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116583","url":null,"abstract":"<p><p>Hura crepitans (Euphorbiaceae), is widespread in the Amazon rainforest and on plantations in sub-Saharan Africa. This tree produces an irritating milky latex rich in secondary metabolites, notably daphnane-type diterpenes and cerebrosides. Previous studies have shown that huratoxin, the main daphnane in the latex, significantly and selectively inhibited the growth of colorectal cancer cells through a unique mechanism involving the activation of PKCζ. One major challenge in isolating active molecules from natural products is the accessibility of the resource. This study explores the phytochemical composition and cytotoxic activities of latexes collected in Peru, Benin, and Togo using UHPLC-MS and metabolomics tools to identify a renewable source of bioactive compounds. Significant inter- and intra-continental differences in chemical composition have been highlighted, with daphnanes being concentrated in the Peruvian samples. Extracts form latexes collected in Peru showed cytostatic activity on Caco-2 cells, correlated with the presence of daphnanes, while some African samples exhibited cytotoxic activity on Jurkat and Hela cancer cell lines, leading to the identification of potential other new bioactive compounds such as elasterol and cerebrosides. OBJECTIVE: To compare the composition of different Hura crepitans latex samples and determine their cytotoxic activity in order to identify new bioactive compounds CONCLUSIONS: Inter- and intra-continental variations in the phytochemical composition of latex were observed, leading to significant cytotoxic activities on different cell lines. Daphnanes were identified as responsible for the activity on Caco-2 cells, while elasterol and cerebrosides were putatively associated with the activity on Hela cells.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116583"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822283","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":"Dual recombinase polymerase amplification system combined with lateral flow immunoassay for simultaneous detection of Staphylococcus aureus and Vibrio parahaemolyticus.","authors":"Yan Zhang, Xiaofeng Liu, Jiawei Luo, Hua Liu, You Li, Juan Liu, Lemei Zhu, Jinbin Wang, Haijuan Zeng","doi":"10.1016/j.jpba.2024.116621","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116621","url":null,"abstract":"<p><p>Development of a highly sensitive visualization platform for multiplex genetic detection could significantly improve efficiency and reliability of on-site detection of foodborne pathogens. In this study, coupling recombinase polymerase amplification (RPA) with lateral flow immunoassay (LFIA) readout system was proposed for Staphylococcus aureus and Vibrio parahaemolyticus detection. Taking the advantage of the isothermal amplification of RPA, dual primers modified with different labeling groups were designed to realize target signal amplification. LFIA coated with anti-digoxigenin antibody and streptavidin as test line 1 and 2 were designed to detect the two RPA products. The proposed method (dual RPA-LFIA) could realize visual detection using LFIA through rapid RPA amplification within 20 min, exhibiting a lowest detection limit of 4.6 × 10² CFU/mL for Staphylococcus aureus and Vibrio parahaemolyticus. The dual RPA-LFIA is characterized by simultaneous detection of dual targets in one RPA reaction and colorimetric readout through LFIA, thus ensuring high sensitivity and efficiency, and showing great potential to address the on-site detection of foodborne pathogens in the future.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116621"},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791504","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":"Unsaturated fatty acid profiles and prognostic significance in epilepsy patients: A comprehensive analysis using UPLC-MS/MS and SVM algorithm.","authors":"Xiuwei Shen, Jiaying Wu, Tao Zhou, Yanwen Xu, Siyu Zhuo, Fangfang Zheng, Shuhua Tong, Xiuhua Zhang, Lufeng Hu","doi":"10.1016/j.jpba.2024.116610","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116610","url":null,"abstract":"<p><p>Unsaturated fatty acids (UFAs) play a crucial physiological role in human body. However, the concentration-related changes and prognostic significance of UFAs in epilepsyremain unclear. An optimized ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed to measure six key UFAs: oleic acid (OA), linoleic acid (LA), arachidonic acid (AA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Subsequently, the levels of these six UFAs were determined in 40 healthy individuals and 49 epilepsy patients. The diagnostic value of UFAs and clinical examination indicators were assessed using statistical analysis and the support vector machine (SVM) algorithm. The results showed that the UPLC-MS/MS method successfully quantified the levels of OA, LA, AA, ALA, EPA, and DHA in both the healthy individuals and epilepsy patients. Compared with the healthy group, the levels of ALA, AA, and DHA were significantly elevated in the epilepsy group (P < 0.05). Pearson correlation analysis revealed a strong positive correlation among the UFAs in the epilepsy group. The orthogonal partial least squares-discriminant analysis (OPLS-DA) model showed that DHA and EPA were more important than cholesterol in distinguishing between two groups, although the separation was not complete. The SVM model achieved better separation, with an area under the curve (AUC) of 0.95 when including the six UFAs. The EPA/DHA ratio was identified as a key feature, with a significant contribution to the model's performance. Removing the six UFAs from the model reduced the AUC to 0.91, highlighting the predictive value of UFAs for epilepsy. In conclusion, ALA, AA, and DHA, are altered in epilepsy patients. The EPA/DHA ratio was found to be a key predictive indicator for epilepsy. The use of UFAs in conjunction with clinical examination data improved the predictive power of the SVM model, suggesting that UFAs have potential as biomarkers for epilepsy.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116610"},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807059","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":"Metabolic characteristics of prostate cancer cells with high metastatic potential revealed by (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate inhibition.","authors":"Baoyan Ding, Wei Meng, Xiaoling Zang, Zhihua Lv","doi":"10.1016/j.jpba.2024.116611","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116611","url":null,"abstract":"<p><p>A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145). SEC also caused the decrease of extracellular N1-acetylspermidine (LNCaP), erythronic acid/threonic acid (PC3 and DU145), and nicotinic acid/picolinic acid (DU145), and the increase of extracellular 5'-methylthioadenosine (DU145). High metastatic PC3 and DU145 cells exhibited changes in aromatic amino acid metabolism including tyrosine metabolism, phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism (PC3 and DU145), TCA cycle (PC3), arginine and proline metabolism, and glycerophospholipid metabolism (DU145), different from the low metastatic LNCaP cells, which had changes in alanine, aspartate, and glutamate metabolism, and arginine biosynthesis. In addition, the levels of p-mTOR and p-AMPK were shown to be obviously downregulated and upregulated, respectively, in high metastatic PC3 and DU145 cells upon SEC inhibition, while this behavior was not detected in LNCaP cells.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116611"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813605","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 of an LC-MS/MS method for the simultaneous quantification of 11 perfluoroalkyl compounds in mouse plasma for toxicokinetic applications.","authors":"Chloé Ml Argoul, Yannick Dauwe, Laïla Lakhal, Pierre-Louis Toutain, Nicole Picard-Hagen, Véronique Gayrard, Marlène Z Lacroix","doi":"10.1016/j.jpba.2024.116596","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116596","url":null,"abstract":"<p><p>Following regulatory pressure, the manufacture of long-chain per- and polyfluoroalkyl substances (PFAS) has been phased out, and alternatives such as short-chain homologs and ether-PFAS have replaced the bioaccumulative long-chain PFAS. However, data are lacking regarding the toxicokinetic (TK) properties of certain PFAS, particularly emergent substitutes for long-chain compounds. Additionally, the existing analytical methods used for TK studies measure a single compound or only a few simultaneously. For this reason, an LC-MS/MS method was developed for the simultaneous quantification in mouse plasma of 11 PFAS representative of some of the most important categories of these compounds, for application in TK studies. The method was successfully validated in the range of 0.5-1000 ng/mL, in accordance with the European Medicines Agency guidelines, and applied to a 24-h pilot TK study conducted in mice. All compounds were monitored over 24 hours in the pilot study. The present method is therefore suitable for the simultaneous quantification of PFAS in plasma samples and can be applied for future TK studies.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116596"},"PeriodicalIF":3.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790644","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":"LAP-MALDI MS analysis of amelogenin from teeth for biological sex estimation.","authors":"Lily R Adair, Mary E Lewis, Matthew J Collins, Rainer Cramer","doi":"10.1016/j.jpba.2024.116599","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116599","url":null,"abstract":"<p><p>The biological sex estimation of human individuals can be achieved by extracting fragments of the amelogenin protein from small areas of tooth enamel. The amelogenin gene can be found on both sex chromosomes (X and Y) with chromosome-specific differences in its sequence, and consequently the sequences of the expressed protein in teeth. Virtually all current analytical techniques used to identify the occurrence of the male Y chromosome-specific proteoform employ proteoform-specific peptide analysis by LC-ESI MS/MS, which typically results in longer analytical times due to the LC separation step, despite recent efforts of shortening the LC step. We report a rapid analytical workflow for biological sex estimation by combining minimal acid extraction of amelogenin peptides, including the Y chromosome-specific SM_oxIRPPY peptide, with LAP-MALDI (liquid atmospheric pressure matrix-assisted laser desorption/ionization) MS and MS/MS analysis but without the use of an LC system. A total of 27 peptides from amelogenin and ameloblastin were characterized by MS/MS, revealing oxidation and deamidation as chemical modifications and information on the maturation of amelogenin. The entire sample preparation and analysis time for biological sex estimation using the applied workflow is ≤ 10 minutes, of which only 1 minute is needed for the MS and MS/MS data acquisition. The sample preparation is minimally hazardous, requiring 10 % HCl for peptide extraction, and can be undertaken in non-specialized labs before being submitted to MS and MS/MS analysis. The developed workflow can also facilitate the MS/MS analysis of many other amelogenin peptides without LC separation, providing further proteomic information on protein expression and mRNA transcription. It was applied to the teeth of five males and five females, whose biological sex had been estimated using osteological techniques, from three archaeological sites.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116599"},"PeriodicalIF":3.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791762","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":"Deeper insights into the stability of oxylipins in human plasma across multiple freeze-thaw cycles and storage conditions.","authors":"Maria Moran-Garrido, Sandra M Camunas-Alberca, Jorge Sáiz, Ana Gradillas, Ameer Y Taha, Coral Barbas","doi":"10.1016/j.jpba.2024.116587","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116587","url":null,"abstract":"<p><p>Oxylipins are signaling lipids derived from the oxidation of polyunsaturated fatty acids (PUFAs). In lipidomic studies, human plasma may be subjected to various storage conditions and freeze-thaw cycles, which may impact the analysis of these compounds. In this study, we used liquid chromatography coupled with mass spectrometry (LC-MS) to examine the influence of up to five freeze-thaw cycles (FTCs) on free and total (mostly esterified) oxylipins in human plasma and the influence of temperature and storage duration (4 °C for up to 120 h and -20 °C and -80 °C for 1-98 days) in the presence or absence of butylated hydroxytoluene (BHT) on extracted oxylipins stored in LC-MS amber vials. In fresh plasma subjected to several FTCs, approximately 48 % of the detected free oxylipins were significantly altered by the third cycle, with increases in cytochrome P450 (CYP450) and lipoxygenase (LOX)-derived compounds and reductions in trihydroxylated oxylipins. In contrast, multiple FTCs did not significantly alter esterified oxylipins. At 4 °C, the extracted oxylipins did not change significantly for up to 120 h (5 days). Oxylipin levels remained stable for 98 days at -80 °C but decreased by 98 days at -20 °C. The antioxidant activity of butylated hydroxytoluene (BHT) did not influence oxylipin stability at 4 °C for 120 h or at -80 °C for 98 days, but it reduced oxylipin degradation at -20 °C at 98 days. Conversely, prostaglandin F_2α (PGF_2α) exhibited substantial increases at -20 °C and -80 °C, independent of BHT. This study demonstrates that (i) unlike free oxylipins, the esterified oxylipin pool remains stable following repeated FTCs, (ii) extracted oxylipins are stable at 4 °C for up to 120 h and at -80 °C for up to 98 days, but not at -20 °C for 98 days, and (iii) BHT may minimize oxylipin degradation of sample extracts stored at -20 °C. This study provides a framework for measuring oxylipins under various freeze-thaw and storage conditions.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116587"},"PeriodicalIF":3.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794849","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":"Application of a dual channel MPTS-modified two-dimensional cell membrane chromatography system for rapid screening of effective ingredients in Saposhnikovia divaricata targeting inflammatory macrophages and fibroblast synovial cells in the treatment of rheumatoid arthritis.","authors":"Yueyue Li, Yanqiu Gu, Yuhuan Shi, Bin Zhang, Shu Pan, Yifeng Chai, Xiaofei Chen, Yongfang Yuan","doi":"10.1016/j.jpba.2024.116595","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116595","url":null,"abstract":"<p><p>Saposhnikovia divaricata (SD) is a traditional Chinese medicine (TCM) which has been commonly used for the treatment of rheumatoid arthritis (RA). However, its active components and mechanism of anti-RA are still unclear. Targeting rheumatoid arthritis-fibroblastoid synovial (RA-FLS) and synovial macrophages are promising strategies for RA treatment, and their membrane receptors are important targets for anti-RA active substances. A dual channel 3-mercaptopropyltrimethoxysilane (MPTS) modified 2D cell membrane chromatography (CMC) system was established to characterize dual-cell membrane binding active components in SD. Nine components retained on RAW-CMC column and 8 components retained on FLS-CMC column were screened out. Among them, 8 components retained well on both CMC columns. We further validate the pharmacological activity of 5-O-methylvisammioside, 3'-O-angeloylhamaudol, imperatorin, phellopterin and anomalin. They could efficiently target both inflammatory macrophages and fibroblast synovial cells, reduce the release of inflammatory factors, inhibit abnormal cell proliferation, and promote cell apoptosis. 5-O-methylvisammioside, which exhibited the best pharmacological ability on both target cells, inhibited the NF-κB pathway. Our results showed that the dual channel MPTS modified 2D CMC system is a practical method for rapid screening the active components in TCM binding on multiple target cells' membrane protein of a disease. The method is very suitable for elucidating the mechanism of TCM with multiple-components and targets, and rapid screening of lead compounds.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116595"},"PeriodicalIF":3.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780479","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}