Journal of pharmaceutical and biomedical analysis最新文献

{"title":"GC-MS uncovers unique metabolic markers of drug-resistant epilepsy in capillary but not venous dried blood spots.","authors":"Sing Teang Kong, Shih-Hui Lim, Jianhong Ching, Paul Chi-Lui Ho","doi":"10.1016/j.jpba.2024.116561","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116561","url":null,"abstract":"<p><p>This study compared the effectiveness of capillary dried blood spots (DBS) versus venous DBS in detecting metabolic changes related to drug-resistant epilepsy (DRE). DBS samples were collected from 142 epilepsy patients (58 drug-resistant, 84 drug-responsive) via venipuncture or fingerstick capillary sampling. Metabolomic analysis using gas chromatography-mass spectrometry compared DBS metabolite profiles between the two groups. While venous DBS profiles showed no distinct patterns, capillary DBS profiles revealed clustering patterns in principal components analysis, with the first two principal components explaining 14.5 %, and 13.5 % of the total variance, respectively. Orthogonal PLS-DA confirmed group discrimination (R2Y=0.989, Q2=0.742). Drug-resistant patients exhibited elevated capillary DBS levels of glutamine, pyruvic acid, and serine, and decreased palmitic acid compared to drug-responsive patients. Pathway analysis revealed disruptions in amino acid metabolism, neurotransmission, and cellular energy regulation. Elevated glutamine levels may contribute to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission, key factors in epileptogenesis and drug resistance. Capillary DBS, likely enriched with arterial blood supply to the brain, appears to better capture central nervous system metabolic disturbances compared to venous DBS containing systemic contributions. This minimally invasive capillary DBS approach offers effective metabolic profiling of brain conditions like DRE, for monitoring disease progression and treatment response, enhancing personalized patient management in epilepsy.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605045","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":"Combination of plasma-based lipidomics and machine learning provides a useful diagnostic tool for ovarian cancer.","authors":"Jinhua Rong, Guojun Sun, Jing Zhu, Yiming Zhu, Zhongjian Chen","doi":"10.1016/j.jpba.2024.116559","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116559","url":null,"abstract":"<p><p>Ovarian cancer (OC), the second leading cause of death among gynecological cancers, is often diagnosed at an advanced stage due to its asymptomatic nature at early stages. This study aimed to explore the diagnostic potential of plasma-based lipidomics combined with machine learning (ML) in OC. Non-targeted lipidomics analysis was conducted on plasma samples from participants with epithelial ovarian cancer (EOC), benign ovarian tumor (BOT), and healthy control (HC). The samples were randomly divided into a train set and a test set. Differential lipids between groups were selected using two-tailed Student's t-test and partial least squares discriminant analysis (PLS-DA). Both single lipid-based receiver operating characteristic (ROC) model, and multiple lipid-based ML model, were constructed to investigate the diagnostic value of the differential lipids. The results showed several lipids with significant diagnostic potential. ST 27:2;O achieved the highest prediction accuracy of 0.92 in distinguishing EOC from HC. DG 42:2 had the highest prediction accuracy of 0.96 in diagnosing BOT from HC. Cer d18:1/18:0 had the highest prediction accuracy of 0.65 in differentiating EOC from BOT. Furthermore, multiple lipid-based ML models illustrated better diagnostic performance. K-nearest neighbors (k-NN), partial least squares (PLS), and random forest (RF) models achieved the highest prediction accuracy of 0.96 in discriminating EOC from HC. The support vector machine (SVM) model reached the highest prediction accuracy both in distinguishing BOT from HC, and in differentiating EOC from BOT, with accuracies of 1.00 and 0.74, respectively. In conclusion, this study revealed that the combination of plasma-based lipidomics and ML algorithms is an effective method for diagnosing OC.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605043","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":"Analyte and probe melting temperature guided method development strategy for hybridization LC-MS/MS quantification of siRNAs","authors":"Zifeng Song,&nbsp;Angela Lu,&nbsp;Long Yuan","doi":"10.1016/j.jpba.2024.116556","DOIUrl":"10.1016/j.jpba.2024.116556","url":null,"abstract":"<div><div>Small interfering RNA (siRNA) is a novel class of double-stranded oligonucleotide therapeutics rapidly growing in drug research and development. Accurate, sensitive, and reliable quantification of siRNA analytes in biological samples is required to study their pharmacokinetics, toxicokinetics, and biodistribution. Hybridization LC-MS/MS can achieve highly sensitive and specific bioanalysis of single-stranded oligonucleotides, e.g., antisense oligonucleotides (ASOs); however, its application for bioanalysis of siRNA or other double-stranded oligonucleotides is limited. The detailed rationale and principles for assay development are still not well understood. In this work, we systematically evaluated key steps and parameters of hybridization LC-MS/MS assays, including probes (five different types compared), hybridization procedure and temperature, elution temperature, and column temperature using patisiran, an approved siRNA drug, as the test siRNA. Based on the evaluation, a practical and efficient melting temperature (Tm) guided strategy was developed for fast and reliable method development of hybridization LC-MS/MS assays for siRNA bioanalysis. The strategy was successfully applied to siRNA-A, a test siRNA, in mouse plasma over the range of 1.00–1000 ng/mL and the resulting method has been used to support multiple mouse studies. This method-development strategy showed great value as a general approach for other siRNAs or double-stranded oligonucleotides.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiparametric LC-MS/MS method for simultaneous determination of eleven antifungal drugs and metabolites in human plasma","authors":"Jean-Joseph Bendjilali-Sabiani ,&nbsp;Céline Constans ,&nbsp;Olivier Mathieu ,&nbsp;Yoann Cazaubon","doi":"10.1016/j.jpba.2024.116557","DOIUrl":"10.1016/j.jpba.2024.116557","url":null,"abstract":"<div><div>A multiparametric liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous quantification of 11 antifungal drugs and their metabolites in human plasma. This method addresses the critical need for therapeutic drug monitoring in the treatment of invasive fungal infections, which are increasingly prevalent among immunocompromised patients and those in intensive care units. The method quantifies flucytosin, fluconazole, itraconazole, hydroxy-itraconazole, posaconazole, isavuconazole, voriconazole, voriconazole-N-oxide, anidulafungin, caspofungin, and micafungin. Key challenges in method development included optimising mass spectrometer settings, chromatographic conditions, and sample preparation techniques to ensure accurate, sensitive, and specific detection. Validation of this method was conducted in accordance with the guidelines set by the USA Food and drug administration and the European Medicines Agency covering linearity, precision, accuracy, selectivity, matrix effect, and stability. The method exhibited robust performance with intra- and inter-assay precision under 10 % and average accuracy for intra- and inter-assay comparison of −2.35 % and 0.80 %, respectively. Limits of detection (0.002 to 0.110 mg/L) and a quantification range between 0.005 and 200 mg/L make this method suitable for clinical TDM applications. The ability to simultaneously analyse eleven antifungals and their metabolites within a single 5-minute run enhances its utility in clinical settings, particularly for critically ill patients who may experience significant pharmacokinetic variations. The method requires only 100 µL of plasma, demonstrating good analytical performances rendering it a valuable tool for optimising antifungal therapy and improving patient outcomes in ICU management.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New metabolites of methyltrienolone by in vitro human microsome and characterized using Liquid Chromatography/High Resolution Mass Spectrometry for doping control purposes","authors":"Xiya Yan ,&nbsp;Jinghua Hou ,&nbsp;Siyu Yan ,&nbsp;Wei Chang ,&nbsp;Lisi Zhang ,&nbsp;Zhanliang Wang ,&nbsp;Sheng Yang","doi":"10.1016/j.jpba.2024.116552","DOIUrl":"10.1016/j.jpba.2024.116552","url":null,"abstract":"<div><div>Methyltrienolone (17β-hydroxy-17α-methylestra-4,9,11-trien-3-one) is one of the anabolic androgenic steroids (AAS) banned by the World Anti-Doping Agency (WADA). The biotransformation of methyltrienolone is performed in vitro by human hepatocytes microsomes. Both phase I and phase II experiments are investigated. The incubation samples were extracted and injected to Liquid Chromatography/High Resolution Mass Spectrometry (LC-HRMS), or reacted with methoxylamine (29 Da added) or hydroxylamine (15 Da added), to increase the detection sensitivity. The extracted ion chromatograms of the negative control and the positive samples are compared, and 7 groups of phase I metabolites were found. The metabolic pathways including 17-epimerization, mono-hydroxylation, dihydroxylation, reduced combining mono- or dihydroxylation, as well as 18-nor which are observed and tentatively identified according to the mass spectra by high resolution mass spectrometry. The 18-nor metabolites will potentially be the long-term metabolite in doping control analysis. Its main phase II metabolites, glucuronides of metabolites are all obtained and analyzed.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546063","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":"Altered gut metabolites and metabolic reprogramming involved in the pathogenesis of colitis-associated colorectal cancer and the transition of colon \"inflammation to cancer\"","authors":"Dunfang Wang ,&nbsp;Lin Zhu ,&nbsp;Haifan Liu ,&nbsp;Xue Feng ,&nbsp;Caijuan Zhang ,&nbsp;Bin Liu ,&nbsp;Tao Li ,&nbsp;Li Liu ,&nbsp;Hao Chang ,&nbsp;Jingwei Sun ,&nbsp;Lei Yang ,&nbsp;Weipeng Yang","doi":"10.1016/j.jpba.2024.116553","DOIUrl":"10.1016/j.jpba.2024.116553","url":null,"abstract":"<div><div>Colitis-associated colorectal cancer (CAC) is fatal and can develop spontaneously or as a complication of inflammatory bowel diseases. Although co-administration of azoxymethane/dextran sulfate sodium (AOM/DSS) is a classic method for CAC modeling, its limitations need to be addressed. Accordingly, we aimed to optimize the AOM/DSS model to study CAC extensively and further investigate its pathogenic mechanisms relative to microbiota and metabolism. We optimized the CAC model via a single or enhanced injection of AOM combined with different administration modes and varying DSS concentrations. Subsequently, the fecal-microbiota composition was examined using 16S RNA sequencing, and fecal-colon-metabolome profiles were evaluated via ultra-high performance liquid chromatography-mass spectrometry. Two interval injections of AOM combined with 1.5 % DSS-free drinking resulted in a high tumor formation rate, uniform tumor formation, and low mortality. Based on this model, we innovatively divided the pathogenesis of CAC into three stages, namely inflammation induction, proliferation initiation, and tumorigenesis, and examined the pathological characteristics in each stage. Gut microbial dysbiosis and metabolic alteration drove colorectal tumorigenesis by aggravating inflammation while promoting cell proliferation and carcinogenesis in mice. For the first time, we dynamically demonstrated the process of colon \"inflammation to cancer\" transformation and provided novel insights to clarify the role of amino acid metabolism in the formation of CAC.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561382","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":"Nanomaterial-based magnetic solid-phase extraction in pharmaceutical and biomedical analysis","authors":"Jingxin Hou ,&nbsp;Cong Hu ,&nbsp;Hanyin Li ,&nbsp;Hongmei Liu ,&nbsp;Yangjiayi Xiang ,&nbsp;Gou Wu ,&nbsp;Yan Li","doi":"10.1016/j.jpba.2024.116543","DOIUrl":"10.1016/j.jpba.2024.116543","url":null,"abstract":"<div><div>Magnetic solid-phase extraction (MSPE) holds significant scientific and technological interest as a novel sample preparation method for complex samples due to its easy operation, swift separation, high adsorption efficiency, and environmental friendliness. As the core of MSPE, magnetic sorbents have captured tremendous attention in recent years. Various promising nanomaterials, such as metal-organic frameworks and covalent organic frameworks, have been synthesized and utilized as sorbents in pharmaceutical and biomedical analysis. This review intends to (1) summarize recent progress of magnetic sorbents applied in this area and discuss their advantages, disadvantages, possible interaction mechanisms with the target substances; (2) explore their innovative applications in the analysis of pharmaceuticals, proteins, peptides, nucleic acids, nucleosides, metabolites, and other disease biomarkers from 2021 to 2024; (3) present the integration of MSPE with emerging analytical technologies; and (4) discuss the current challenges and future perspectives. It is expected to provide references and insights for the development of novel magnetic sorbents and their applications in bioanalysis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561381","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":"Integrating 2D NMR-based metabolomics and in vitro assays to explore the potential viability of cultivated Ophiocordyceps sinensis as an alternative to the wild counterpart","authors":"Xiu Gu ,&nbsp;Yanping Li ,&nbsp;Yang Li ,&nbsp;Xiaohui Duan ,&nbsp;Youfan Hu ,&nbsp;Jialuo Chen ,&nbsp;Huan Du ,&nbsp;Jing Bai ,&nbsp;Chengyan He ,&nbsp;Caihong Bai ,&nbsp;Jinlin Guo ,&nbsp;Jiahui Yang ,&nbsp;Kaifeng Hu","doi":"10.1016/j.jpba.2024.116551","DOIUrl":"10.1016/j.jpba.2024.116551","url":null,"abstract":"<div><div><em>Ophiocordyceps sinensis</em> is widely used to treat various diseases and as a health supplement. The present study comprehensively compared the metabolic differences between wild and cultivated <em>O. sinensis</em> through 2D ¹H-¹³C HSQC-based metabolomics, and assessed their anti-lung cancer activity on A549 cells. To characterize the global metabolic profile, sample preparation was scrutinously optimized, and both polar (1:4 methanol-water) and non-polar (1:4 methanol-chloroform) extracts of <em>O. sinensis</em> were investigated. A total of 47 and 10 metabolites were identified in the polar and non-polar extracts, respectively. Principal Component Analysis (PCA) revealed greater differences between the two types of <em>O. sinensis</em> in the polar extracts than in the non-polar extracts. Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) together with univariate tests captured 23 and 19 differential spectral features (with 22 and 11 of them assigned) between wild and cultivated <em>O. sinensis</em> in the polar and non-polar extracts, respectively. Meanwhile, the anti-lung cancer activities of both polar and non-polar extracts of wild and cultivated <em>O. sinensis</em> were assessed by MTS assay on A549 cells, and the sterols found in non-polar extracts, such as ergosterol, ergosterol peroxide, and 9,11-dehydroergosterol peroxide, and β-sitosterol, are the active ingredients with potential anti-lung cancer properties. In this study, we introduced a comprehensive strategy integrating 2D NMR-based metabolomics with <em>in vitro</em> assays for comparing the chemical composition and assessing the pharmacological activity of wild and cultivated <em>O. sinensis</em>. Our results provided a scientific basis for the potential viability of cultivated <em>O. sinensis</em> as an alternative to the wild counterpart.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568974","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":"Metabolomics of Withania somnifera L. extracts by an integrated LC-MS and NMR approach and evaluation of their tyrosinase inhibitory activity","authors":"Luciana Maria Polcaro ,&nbsp;Antonietta Cerulli ,&nbsp;Milena Masullo ,&nbsp;Sonia Piacente","doi":"10.1016/j.jpba.2024.116520","DOIUrl":"10.1016/j.jpba.2024.116520","url":null,"abstract":"<div><div><em>Withania somnifera</em> L. (Solanaceae), for over 3000 years, has been considered an essential herb in Ayurvedic medicine. The roots of <em>W. somnifera</em> contain metabolites mainly belonging to steroidal lactones called withanolides, which possess various pharmacological activities such as neuroprotective, cardioprotective, anti-diabetic, antioxidant and anti-inflammatory. Since the demand on the market for <em>W. somnifera</em> extracts is increasing, with the aim to find an ecological and environmentally friendly strategy of extraction, the roots were submitted to different extraction techniques (macerations, ultrasound-assisted extraction and solid-liquid dynamic extraction) using EtOH:H₂O 50:50, 75:25, 100:0. <em>W. somnifera</em> extracts were investigated by an integrated LC-ESI/QExactive/MS/MS and NMR approach to obtain comprehensive metabolite profiles. Principal Component Analysis of LC-MS and NMR data revealed how the extraction method and the solvent can affect the chemical profile of the extracts. Extracts obtained by maceration exhibited the highest amount of withanolides and withanosides, while the SLDE-Naviglio EtOH extract showed the highest amount of metabolites as benzoic acid, tropane alkaloids and sarcosine, reported for their CNS activity. Moreover, based on the use of this plant in the treatment of neurological disorders, the tyrosinase inhibitory activity of all the extracts was herein tested by spectrophotometric assay, showing IC₅₀ values in a range of 32.86–85.36 µg/ml.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of four-dimensional proteomics and network pharmacology to reveal molecular mechanisms of multi-components multi-targets effects of Sini decoction on myocardial infarction","authors":"Xin Ding ,&nbsp;Min Xu ,&nbsp;Ya Zhang ,&nbsp;Cuiping Long ,&nbsp;Xuemei Su ,&nbsp;Yang Zhang ,&nbsp;Yan Qiao ,&nbsp;Xingxing Zhang ,&nbsp;Qian Zhou ,&nbsp;Guangguo Tan ,&nbsp;Jing Ma","doi":"10.1016/j.jpba.2024.116526","DOIUrl":"10.1016/j.jpba.2024.116526","url":null,"abstract":"<div><div><em>Sini</em> Decoction (SND) has been proven to be an effective formula to alleviate cardiac injury of myocardial infarction (MI). However, the potential mechanism of SND remains unclear. In this study, the MI rat model was established by ligating the left anterior descending coronary artery. A total of 17 SND-distributed components in heart were identified by using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS). The combination of four-dimensional (4D) proteomics and network pharmacology was employed to find the potential targets for therapeutic intervention, and molecular docking and cellular thermal shift assay (CETSA) were used to reveal the interactions between the potential targets and the potential active components distributed in heart of SND. 33 SND-effected proteins were identified by 4D proteomics, which was involved in carbon metabolism, fatty acid metabolism, valine, leucine and isoleucine degradation, tricarboxylic acid (TCA) cycle and PPAR signaling pathway. 17 potential SND-targeted direct proteins were screened by comparing SND-effected proteins generated from 4D proteomics with the MI-related proteins obtained from disease database. The potential relationships between 17 components and 17 potential SND-targeted direct proteins were established by molecular docking analysis, in which songorine, benzoylhypaconine, hypaconine, formononetin, and liquiritigenin could be bound to the surrounding amino acid residues in the binding pocket of Mtor, Parp1, Acadm, Crat, and Aldh2. Then, CETSA analysis further confirmed that songorine and benzoylhypaconine could increase the heat stability of Mtor and Parp1 in cardiac tissue lysate, respectively, which suggested that there existed direct interactions between songorine and Mtor, and benzoylhypaconine and Parp1. In summary, this work concluded that SND produced cardioprotective effects mainly through preserving energy metabolism, also demonstrated that the combination of 4D proteomics and network pharmacology was a promising tool for uncovering the molecular mechanisms of multi-components multi-targets effects of TCM.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561383","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}