INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Kewei Zheng,Yuanyuan Wu,Qingfei Dai,Xiaojun Yan,Yu Liu,Di Sun,Zhongjie Yu,Shuoqi Jiang,Qingbao Ma,Wei Jiang
The objective of this study was to explore the potential of Antarctic krill-derived peptides as α-glucosidase inhibitors for the treatment of type 2 diabetes. The enzymolysis conditions of α-glucosidase inhibitory peptides were optimized by response surface methodology (RSM), a statistical method that efficiently determines optimal conditions with a limited number of experiments. Gel chromatography and LC-MS/MS techniques were utilized to determine the molecular weight (M w ) distribution and sequences of the hydrolysates. The identification and analysis of the mechanism behind α-glucosidase inhibitory peptides were conducted through conventional and computer-assisted techniques. The binding affinities between peptides and α-glucosidase were further validated using BLI (biolayer interferometry) assay. The results revealed that hydrolysates generated by neutrase exhibited the highest α-glucosidase inhibition rate. Optimal conditions for hydrolysis were determined to be an enzyme concentration of 6 × 10 3 U/g, hydrolysis time of 5.4 h, and hydrolysis temperature of 45 °C. Four peptides (LPFQR, PSFD, PSFDF, VPFPR) with strong binding affinities to the active site of α-glucosidase, primarily through hydrogen bonding and hydrophobic interactions. This study highlights the prospective utility of Antarctic krill-derived peptides in curtailing α-glucosidase activity, offering a theoretical foundation for the development of novel α-glucosidase inhibitors and related functional foods to enhance diabetes management.
研究领域:
生物化学
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药理学
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食品科学
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糖尿病研究
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高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-12
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IF 3.8
Shi Qianwen,Wang Shuhui,Wang Gege,Wang Tao,Du Kaili,Gao Cairong,Guo Xiangjie,Fu Shanlin,Yun Keming
Immunoglobulin E (IgE)-mediated immediate hypersensitivity reactions are the most concerning adverse events after penicillin antibiotics (PENs) administration because of their rapid progression and potential for fatal outcome. However, the diagnosis of allergic death is a forensic challenge because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. In this study, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to screen potential forensic biomarkers of fatal anaphylactic shock induced by four PENs (benzylpenicillin (BP), amoxicillin (AMX), oxacillin (OXA), and mezlocillin (MEZ)), and analyzed the metabolites, metabolic pathway and the mechanism which were closely related to the allergic reactions. The metabolomics results discovered that a total of 24 different metabolites in all four anaphylactic death (AD) groups, seven of which were common metabolites. A biomarker model consisting of six common metabolites (linoleic acid, prostaglandin D2, lysophosphatidylcholine (18:0), N-acetylhistamine, citric acid and indolelactic acid) AUC value of Receiver Operating Characteristic (ROC) curve was 0.978. Metabolism pathway analysis revealed that the pathogenesis of PENs-induced AD is closely related to linoleic acid metabolism. Our results revealed that the metabolomic profiling has potential in PENs-induced AD post-mortem diagnosis and metabolic mechanism investigations.
研究领域:
药理学
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毒理学
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法医学
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代谢组学
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PubMed
高影响因子
Pharmaceutics
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2024
·Vol. 16
·期 5
·591
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IF 4.9
Liang Wu,Danfeng Li,Peijing Wang,Linling Dong,Wang Zhang,Jianjun Xu,Xiaoliang Jin
Pedunculoside, a triterpene saponin derived from variousIlexspecies, holds potential as a treatment for cardiovascular diseases. However, its clinical application is hindered by poor bioavailability, rapid elimination, and extensive intestinal metabolism to rotundic acid. To address these issues, a water-soluble inclusion complex of pedunculoside, namely, the beta-CD polymer inclusion complex of pedunculoside (pedunculoside–βCDP), was prepared in this study, and a comparative in vitro stability and pharmacokinetic behavior study was performed between pedunculoside and pedunculoside–βCDP. Both pedunculoside and pedunculoside–βCDP exhibited the highest stability in simulated gastric fluid and simulated intestinal fluid but were readily metabolized when co-incubated withBifidobacterium adolescentisandBifidobacterium breve. An LC-MS/MS analytical method for the simultaneous determination of pedunculoside and rotundic acid in rat plasma was successfully established, validated, and applied to investigate the pharmacokinetic behavior after rats were intravenously administered with pedunculoside or pedunculoside–βCDP. The results indicated that pedunculoside–βCDP could significantly improve the pharmacokinetic profile of pedunculoside by increasing plasma exposure, retarding elimination, and reducing intestinal metabolism. This study enhances our understanding of pedunculoside–βCDP’s metabolic fate and pharmacokinetic properties and potentially advances its further research, development, and clinical application.
研究领域:
药理学
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药物递送系统
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分析化学
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心血管研究
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高影响因子
MATERIALS RESEARCH BULLETIN
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2025
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IF 5.7
Ying Li,Huaping Xiong,Wei Shi,Zheming Ni,Shengjie Xia
Defect engineering and heterostructure construction are important strategies to enhance the photocatalytic performance of single-phase materials. In this study, an O- and Cd-dual-defect-modified LaOCl@CdS heterojunction (Ov-L@Cdv-C) was successfully constructed. Under visible light irradiation, using the typical fluoroquinolone antibiotic ciprofloxacin (CIP) as the target pollutant, Ov-L@Cdv-C exhibited superior photocatalytic degradation performance compared to Ov-LaOCl and Ov-L@CdS. Under optimal conditions (0.5 g/L catalyst, 0.010 g/L initial CIP concentration, pH = 5), the degradation efficiency of CIP reached 84.79 % within 150 min, significantly higher than that of Ov-LaOCl (48.73 %) and Ov-L@CdS (71.96 %). XPS and EPR characterizations confirmed the presence of abundant O and Cd dual defects in the Ov-L@Cdv-C heterojunction. ESR and free radical quenching experiments revealed that the main reactive species during the degradation process were ·O 2 − and h⁺. Based on work function calculations and built-in electric field analysis, a Z-scheme photocatalytic mechanism for the Ov-L@Cdv-C dual-defect heterojunction was proposed. Furthermore, LC-MS analysis identified the degradation intermediates and proposed three possible degradation pathways. In addition, T.E.S.T. predictions indicated that the toxicity of CIP gradually decreased during the photocatalytic degradation process.
研究领域:
环境科学
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催化
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材料科学
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化学工程
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光化学
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分析化学
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毒理学
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Jiangbin Han,Lijuan Zhai,Jie Wang,Biying Dai,Huiyue Lu,Jiao Chen,Xiaoli Wang,Yuyu Wu,Wen Qian
Hetrombopag (Hengqu®) is an oral nonpeptide thrombopoietin receptor agonist for the treatment of thrombocytopenia and aplastic anemia. Research on the pharmacokinetic behavior is very important, but accurate quantification of metal-sensitive hetrombopag in biological specimens is a challenging analytical problem. In view of the presence of trace metals from a variety of sources, such as chromatographic system, containers, and the mass spectrometry spray needle, which can contribute to poor peak shape, tailing, and diminished recovery of compound. To ameliorate these problems, different solvent additives, mobile phase, containers and precipitant reagents were investigated to reduce the negative effects. In the present study, a robust, selective, and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of hetrombopag in dog plasma was developed based on the dual strategies: (1) 6 % perchloric acid in acetonitrile eliminates metal ion adsorption in storage containers, and (2) 0.01 % trifluoroacetic acid (TFA) in the mobile phase suppresses chelation in chromatographic systems. These two solvents are essential requirements for ensuring stable analytical signals. This method employed an InfinityLab Poroshell 120 EC-C18 column (4.6 ×50 mm, 2.7 μm, Agilent) with a gradient system comprising 0.01 % trifluoroacetic acid with 10 mM ammonium formate (phase A) and a mixture of H 2 O: methanol: isopropanol (1:10:10, v/v/v) containing 0.01 % trifluoroacetic acid and 10 mM ammonium formate (phase B). The column temperature of 50℃ and the addition of isopropanol were beneficial for the separation of interfering peaks and target analyte peaks in plasma. The method exhibits excellent linearity over 3 orders of magnitude. The method achieved a lower limit of quantification (LLOQ) of 0.10 ng/mL using only 50 μL of plasma, with precision (RSD ≤ 8.83 %) and accuracy (88.4–102.2 %) within acceptable limits. The method was applied to determine the plasma concentration of hetrombopag in eight male beagle dogs after each administration of three 2.5 mg hetrombopag tablets. The analytical methodology described in the present work should be useful in the future work aiming to establish a model relating metal-sensitive other compounds.
研究领域:
分析化学
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药代动力学
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生物分析
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质谱分析
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药物研发
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高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2024
·Vol. 416
·期 29
·7043-7062
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IF 3.8
Liu Wen-Ya,Xu Di,Meng Hui-Hui,Wang Cheng-Yao,Feng Xin,Wang Jun-Song
Cucurbitacin B (CuB) is a natural triterpenoid with diverse pharmacological effects including potent anticancer activity. However, its oral bioavailability is hampered by limited metabolism in vivo. We characterized CuB’s in vivo metabolism in rats to uncover bioactive metabolites retaining therapeutic potential, using a robust UHPLC-Q-TOF–MS/MS workflow. This workflow combined molecular networking, fragmentation filtering, and mass defect filtering to identify CuB metabolites in rat urine, plasma, and feces following oral administration. Thirteen metabolites were identified and seven were confirmed. Major phase I transformations involved hydrolysis, reduction, epoxidation, and amination. Phase II conjugation included cysteine, glutathione, glucuronide, and gluconic acid conjugates. Notably, one of the main metabolites formed was the cysteine conjugate CuB-Cys. CuB-Cys maintained similar in vitro antiproliferative activity to CuB on HepG2, MCF-7, and PANC-1 cancer cell lines. However, it demonstrated lower cytotoxicity towards non-cancerous L02 cells, highlighting improved therapeutic selectivity. Mechanistically, CuB-Cys induced greater apoptotic signaling in HepG2 cells than CuB via enhanced caspase activation and disrupted BAX-Bcl-2 balance. This represents the first systematic characterization of CuB’s in vivo metabolic pathway. The identification and confirmation of CuB-Cys provide insight for drug development efforts aiming to maintain therapeutic efficacy while reducing toxicity, via metabolite-based approaches. Our findings shed light on strategies for improving CuB’s clinical potential. Graphical Abstract
研究领域:
药理学
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代谢组学
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肿瘤学
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Toxicologie Analytique et Clinique
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2025
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IF 1.7
Xiaolong Zhang,Kundi Zhao,Yuxuan Chen,Jinlei Liu,Jie Gu,Mengchao Wang,Yinyin Dai,Huimin Zhang,Amin Wurita,Koutaro Hasegawa
Summary Introduction Distribution of imidazole-derived GABA agonists, such as etomidate, metomidate and its analogs have been encountered frequently especially in China, along with its abuse cases. Recently, we were enquired to investigate urine samples and dubious powder seized from abuse cases, in which a new etomidate analog isopropoxate was detected. Methods The etomidate analog contained in the seized powder was tried to be identified using gas chromatography-mass spectrometry and by hydrolysis its ester structure to related alcohol under basic reaction environment, as a preliminary analysis for the powder composition. Reference standard were then purchased to identify the compound in suspected powder. For urine samples, after adding the internal standard and acetonitrile to the urine samples followed by vortexing and centrifugation, the supernatant layer was analyzed by LC-MS/MS. Results For LC-MS/MS analysis, the coefficient of determination (r2) values of the calibration curves of etomidate acid and isopropoxate in the urine were more than 0.99; the limits of detection (LODs) for etomidate acid, and isopropoxate was 0.025 ng/mL; the limits of quantification (LOQs) of them was 0.05 ng/mL. Etomidate acid and isopropoxate could be determined from submitted urines. And nine isopropoxate metabolites and their major metabolic pathways were identified. Conclusions In this study, we have established a simultaneous and reliable analytical method for etomidate acid and isopropoxate in human urine by LC-MS/MS, and the method could be applied to authentic cases. It is also the first time that the metabolic pathway of isopropoxate in the human body has been explored.
研究领域:
毒理学
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分析化学
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法医学
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高影响因子
CHROMATOGRAPHIA
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2024
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IF 1.2
Han Kyoung-Moon,Woo In Suk,Park Chae Gyeong,Kim You Kyung,Yang Yoon Ji,Park Bo Reum,Choi Jang Duck,Son Kyung Hun
Preservatives can be used in natural and organic cosmetics to prevent quality deterioration during distribution and use, but the ingredients permitted are limited in the Republic of Korea. A method of simultaneous analysis was developed to monitor natural and organic cosmetics distributed online for the presence of 15 illegally used preservatives. Considering the complexities of the cosmetic matrices, an optimized sample preparation method is essential. Therefore, we developed the optimal purification method by comparing three preparation methods: QuEChERS, high-speed centrifugation, and solid-phase extraction (SPE). The SPE method, which exhibited the most favorable results in matrix reduction, was employed. To establish the SPE-ultra-high-performance liquid chromatography-diode array detection method, factors such as the mobile phase and column were optimized. The optimal separation of the 15 preservatives was observed under the following conditions: mobile phase A comprising 0.1% phosphoric acid in water with 0.5 mM sodium hexanesulfonate and a C 8 column (1.7 μm, 2.1 × 150 mm) as the stationary phase. The linear correlation coefficients were > 0.9998, and the limits of detection and quantitation ranged from 0.05 to 0.67 and 0.15 to 2.02 μg mL −1 , respectively. Using the established analytical method, illegally used preservatives were detected in products claimed to be natural and organic cosmetics sold on the market, and these findings were subsequently verified using liquid chromatography-tandem mass spectrometry. Six out of 47 samples contained phenoxyethanol and parabens. Therefore, this method will help manage the addition of illegal preservatives to natural and organic cosmetics.
研究领域:
分析化学
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化妆品科学
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Zhiqing Zhou,Shiman Zhang,Can Fang,Hong Cheng,Mayire Yasheng,Jinfeng Yuan,Wangyan Cai,Zihan Fang,Fei Wu,Youjie Wang,Zheng Xue,Xinguang Zhang
Platycodonic Radix (PR) is a key herb in traditional Chinese prescriptions for pediatric respiratory disorders. However, its intense bitterness and persistent throat astringency reduce treatment compliance. This study established a mechanism-informed taste-masking strategy integrating chemical profiling, sensory evaluation, and formulation optimization. PR sensory characteristics were first quantified using human panels and an electronic tongue. Subsequently, PR water extracts were characterized by non-targeted profiling based on liquid chromatography-mass spectrometry (LC-MS). Putative bitter constituents were further screened using BitterX-assisted TAS2R molecular docking. The optimized formulation was then validated in two representative pediatric formulas containing the classical “PR- Glycyrrhiza uralensis Fisch.” herb pair. LC-MS tentatively identified 308 compounds in PR decoctions, mainly carbohydrates and glycosides. Docking results indicated that platycodigenin, polygalacic acid, lactone-type platycodins, luteolin, and lignans show high affinity for human bitter taste receptors TAS2R14, TAS2R44, and TAS2R47, confirming a multi-component basis for PR bitterness. Among the excipients tested, 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) and xylitol were most effective. Mechanistically, HP-β-CD primarily suppressed residual bitterness and astringency, whereas xylitol improved initial mouthfeel. An optimized combination of 6.5 % HP-β-CD plus 10 % xylitol (w/w relative to PR) successfully transformed PR decoctions from “difficult to accept” to “sweet with no lingering bitterness”, a shift corroborated by electronic tongue DFA plots. This strategy improved palatability in two representative pediatric formulas without altering the herbal composition. These findings demonstrate that 6.5 % HP-β-CD plus 10 % xylitol effectively alleviates both initial bitterness and throat irritation, offering a practical, non-destructive solution to enhance pediatric medication adherence in traditional phytotherapy. Download: Download high-res image (165KB) Download: Download full-size image
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高影响因子
FITOTERAPIA
·
2025
·
IF 2.6
Xuan Zhang,Jie Weng,Yi Luo,Hongcun Liu,Jing Yan,Zhiqiang Gong,Chaonan Kong,Xue Li,Lifang Yang,Mingguo Jiang
To elucidate the efficacy and potential molecular mechanisms underlying the therapeutic effects of Spatholobi Caulis flavonoids (SCF) in the treatment of primary dysmenorrhea (PD). The present study established oxytocin-induced uterine contractions in vitro and a model of PD in rats evoked by estradiol benzoate and oxytocin. The uterine contraction experiments demonstrated that SCF significantly inhibited uterine smooth muscle tone by 62.07 %. SCF effectively attenuated the torsional response in PD rats, normalised the PGF2α/PGE2 ratio, and reduced NO and Ca 2+ levels. The constituents of SCF were evaluated by using a Liquid Chromatograph Mass Spectrometer(LC-MS) method, and 11 flavonoid components were preliminarily deduced. Network pharmacology and molecular docking (MD) techniques were used to predict therapeutic targets, with the former suggesting key targets such as RhoA, VEGFA, and PIK3CA, while the latter indicated that 10 compounds had a strong binding affinity for RhoA. The expression of CALM, RhoA, ROCK1, PIK3CA, and AKT was down-regulated at both the protein and mRNA levels. Additionally, the expression levels of genes associated with VEGFA, IP3R, MLCK and NOS3 were found to be regulated. The collective evidence from this study suggests that SCF may attenuate uterine spasm by inhibiting the RhoA/ROCK signaling pathway, decreasing the levels of PGF2α, NO and Ca 2+ , and increasing the content of PGE2. This study provides a theoretical basis for the application of SCF in the treatment of PD.
研究领域:
药理学
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分子生物学
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PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 6
·e70108
·
IF 1.7
Ancheng Gu,Chuwen Zhang,Dan Li,Bohong Cen,Wanwen Cao,Zhongyuan Xu
Dapagliflozin is a widely used sodium-glucose cotransporter 2 inhibitor that has been approved for the treatment of Type 2 diabetes. In this study, we present a simple and sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method for the simultaneous quantification of dapagliflozin and its metabolite, dapagliflozin 3-O-glucuronide (D3OG). The experiments were conducted using an Agilent G6495B triple quadrupole mass spectrometer coupled with an Agilent 1290 Infinity II HPLC system, featuring a Poroshell 120 EC-C18 column. Gradient elution was performed with ammonium formate (10 mM) and methanol as the mobile phase. The G6495B was operated in negative ion mode with electrospray ionization and multiple reaction monitoring. The quantitative method was validated according to FDA and EMA guidelines, assessing parameters such as selectivity, linearity, accuracy, precision, dilution integrity, stability, and recovery. Methanol was used as a protein precipitant during sample preparation, resulting in consistent extraction recoveries ranging from 91% to 96% for all analytes. The linear range for the analytes was established at 2–800 μg/L with a sample volume of 100 μL. This validated method is sufficient for the simultaneous quantification of dapagliflozin and D3OG in plasma and has been successfully applied in pharmacokinetic studies, bioequivalence assessments, and clinical therapeutic monitoring. Trial Registration: Chinese Clinical Trial identifier: ChiCTR2100044600
研究领域:
分析化学
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药理学
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临床医学
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高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
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2025
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IF 4.6
Cong Liu,Yanli Dong,Junmin Wang,Qianqian Wang,Chun Wang,Qiuhua Wu
Phenolic environmental endocrine disruptors (EEDs) pose significant risks to the reproductive and nervous systems. Herein, we synthesized a magnetic OH-anchored porous polymer (M-Pue@TB-HCP2) by linking natural puerarin with 1,3,5-tris(bromomethyl)benzene for the first time. M-Pue@TB-HCP2 showed high extraction recovery (94 %-99 %) for phenolic EEDs (bisphenol S, bisphenol A, bisphenol B and p -tert-butylphenol) thanks to its amphiphilic sites supplying hydrogen bonding and π conjugation interaction. Moreover, M-Pue@TB-HCP2 displayed excellent reusability and long service life. Using M-Pue@TB-HCP2 as magnetic solid-phase extraction adsorbent, coupled with high-performance liquid chromatography-mass spectrometry, a novel method was established for detecting trace EEDs from shrimps, achieving low detection limit (0.80–5.50 ng g −1 for green shrimp, 1.00–4.00 ng g −1 for white shrimp), good spiked recovery of 80.3 %-117 %, relative standard deviation less than 5.7 %. The method has the merits of high sensitivity, good accuracy and excellent reproducibility, making it suitable for the trace analysis of EEDs in shrimps. This work not only provides a new option for rapid and accurate detection of trace EEDs in shrimps but also explores a new strategy for the preparation of efficacious adsorbents by utilizing sustainable raw materials.
研究领域:
环境科学
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高分子化学
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分析化学
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食品安全
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内分泌学
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纳米技术
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吸附技术
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高影响因子
危险品化学品经营许可证（带存储）