JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Jincai Wang,Xiaoling Huang,Jie Mei,Xinwei Chen,Rong Ma,Guowei Li,Zhengjin Jiang,Jialiang Guo
In this study, an at-line nanofractionation (ANF) platform was successfully fabricated in parallel with mass spectrometry and trypsin inhibitory bioactivity assessment for rapid screening of trypsin inhibitors (TIs) from natural products for the first time. After systematic optimization, the ANF platform was applied to screen and identify TIs in the extract of a traditional Chinese herb, i.e., Cotinus coggygria Scop. The semi-preparative reverse-phase liquid chromatography was used subsequently to further simplify and enrich the insufficiently separated components. After comprehensive evaluation and validation, the ANF platform successfully identified 12 compounds as potential TIs, including 8 flavonoids and 2 organic acids . Additionally, a comparison study was conducted using two other ligand fishing approaches, i.e., capillary monolithic and magnetic beads-based trypsin-immobilized enzyme microreactors, which successfully identified 8 identical flavonoids as TIs. Importantly, the molecular docking study showed the molecular interactions between enzymes and inhibitors, thus strongly supporting the experimental results. Overall, this work has fully demonstrated the feasibility of the established ANF platform for screening TIs from Cotinus coggygria Scop., and proved its great prospects for screening bioactive components from natural products.
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高影响因子
MOLECULES
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2022
·Vol. 27
·期 20
·6923
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IF 4.927
Jingyi Jian,Jiaming Yuan,Yu Fan,Jincai Wang,Tingting Zhang,Jeroen Kool,Zhengjin Jiang
How to rapidly and accurately screen bioactive components from complex natural products remains a major challenge. In this study, a screening platform for pancreatic lipase (PL) inhibitors was established by combining magnetic beads-based ligand fishing and high-resolution bioassay profiling. This platform was well validated using a mixture of standard compounds, i.e., (-)- epigallocatechin gallate (EGCG), luteolin and schisandrin. The dose–effect relationship of high-resolution bioassay profiling was demonstrated by the standard mixture with different concentrations for each compound. The screening of PL inhibitors from green tea extract at the concentrations of 0.2, 0.5 and 1.0 mg/mL by independent high-resolution bioassay profiling was performed. After sample pre-treatment by ligand fishing, green tea extract at the concentration of 0.2 mg/mL was specifically enriched and simplified, and consequently screened through the high-resolution bioassay profiling. As a result, three PL inhibitors, i.e., EGCG, (-)-Gallocatechin gallate (GCG) and (-)-Epicatechin gallate (ECG), were rapidly identified from the complex matrix. The established platform proved to be capable of enriching affinity binders and eliminating nonbinders in sample pre-treatment by ligand fishing, which overcame the technical challenges of high-resolution bioassay profiling in the aspects of sensitivity and resolution. Meanwhile, the high-resolution bioassay profiling possesses the ability of direct bioactive assessment, parallel structural analysis and identification after separation. The established platform allowed more accurate and rapid screening of PL inhibitors, which greatly facilitated natural product-based drug screening.Keywords:high-resolution bioassay profiling;magnetic beads-based ligand fishing;high-performance liquid chromatography;pancreatic lipase;inhibitor screening
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CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
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2016
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IF 2.217
Xiao-Hua Zhang,Hai-Long Wu,Xiao-Li Yin,Yong Li,Xiang-Dong Qing,Hui-Wen Gu,Chao Kang,Ru-Qin Yu
In this paper, a new strategy of introducing an extra solvent mode in the three-way EEMs data to construct a four-way EX–EM-solvent-samples data set was used in order to investigate the ‘third-order advantage’ by comparing the performances of two four-way calibration algorithms with those of two three-way calibration algorithms. The results of the self-weighted alternating normalized residue fitting (SWANRF) and the parallel factor analysis (PARAFAC) algorithms were both disappointing in this work due to serious collinearity and high background interference. In contrast, the satisfactory results (average recovery, 100.0–107.4% and standard deviation, 1.0–3.0%) were obtained by the third-order calibration methods based on both four-way self-weighted alternating normalized residue fitting (four-way SWANRF) and four-way parallel factor analysis (four-way PARAFAC) algorithms. In addition, for prediction of Dulbecco's modified eagle medium (DMEM) samples, the root-mean-square error of prediction (RMSEP) values for schizandrol B obtained from two three-way calibration algorithms were 60.91 and 35.46 μg mL − 1 with 80% ethanol in the aqueous solvent , which were obviously much larger than these (0.0832 and 0.0825 μg mL − 1 ) obtained using two algorithms of the four-way calibration. The results demonstrated that third-order calibration can extract more inherent information from the data, and can easily solve the problems of serious collinearity and high background interference. In short, among the advantages of this method over the existing methods, low cost, non-toxic and non-destructive analysis can be cited.
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Frontiers in Pharmacology
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2024
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IF 4.4
Zhang Jinpeng,Cui Xinyuan,Zhao Shuo,Chang Zenghui,Zhang Junshuo,Chen Yufeng,Liu Jiale,Sun Guohao,Wang Yiyuan,Liu Yuanyuan
Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer’s disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model.Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group.Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.
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Acta Pharmaceutica Sinica B
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2024
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IF 14.7
Yu Fan,Jincai Wang,Jingyi Jian,Yalei Wen,Jiahao Li,Hao Tian,Jacques Crommen,Wei Bi,Tingting Zhang,Zhengjin Jiang
Human monoamine oxidase B (hMAO-B) has emerged as a pivotal therapeutic target for Parkinson's disease. Due to adverse effects and shortage of commercial drugs, there is a need for novel, highly selective, and reversible hMAO-B inhibitors with good blood-brain barrier permeability. In this study, a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma, which resulted in the discovery of 75 active compounds, including phenolic acids, volatile oils, and phthalides, two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent, selective, reversible and had good blood‒brain permeability. Molecular docking and molecular dynamics simulations elucidated the inhibition mechanism. Sedanolide (IC 50 = 103 nmol/L; SI = 645) and neocnidilide (IC 50 = 131 nmol/L; SI = 207) demonstrated their excellent potential as hMAO-B inhibitors. They offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as rasagiline. In SH-SY5Y cell assays, sedanolide (EC 50 = 0.962 μmol/L) and neocnidilide (EC 50 = 1.161 μmol/L) exhibited significant neuroprotective effects, comparable to the positive drugs rasagiline (EC 50 = 0.896 μmol/L) and safinamide (EC 50 = 1.079 μmol/L). These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.
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Journal of Pharmaceutical Analysis
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2025
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IF 8.9
Jiaming YUAN,Zhuoping ZHENG,Zhongkang WANG,Hao TIAN,Lingling XI,Jacques CROMMEN,Tingting ZHANG,Jincai WANG,Zhengjin JIANG
Catechol-O-methyltransferase (COMT) inhibition is a critical therapeutic strategy for Parkinson’s disease (PD), yet clinical inhibitors face limitations in bioavailability and hepatotoxicity, driving demand for novel natural scaffolds. In this study, we developed an integrated analytical platform by coupling high-resolution bioassay profiling (HRBP) and affinity-based ligand fishing system to effectively characterize bioactive compounds targeting COMT in Paeonia lactiflora Pall. (the most frequently used core herb in tradition Chinese medicine prescriptions for PD treatment). Parallel High-performance liquid chromatography with diode-array detection and tandem mass spectrometry (HPLC-DAD-MS/MS) coupled with nanofractionation enabled real-time bioactivity mapping via 384-well COMT inhibition assays, while semi-preparative liquid chromatography was employed to further identify co-eluted components. HRBP and immobilized COMT ligand fishing identified 16 and 21 candidates, respectively, with 5 overlapping bioactive markers. Notably, the potent inhibitors galloylpaeoniflorin (IC 50 = 16.2 ± 3.4 μM) and 1,2,3,4,6-O-pentagalloylglucose (IC 50 = 3.1 ± 0.5 μM) exhibited comparable potency to the positive control morin (IC 50 = 10.1 ± 0.7 μM). Molecular docking results further revealed the critical interactions and binding sites between the active compounds and COMT. The validated platform demonstrates significant potential for rapid discovery of plant-derived enzyme inhibitors, bridging advanced separation, bioactivity screening, and mechanistic validation in neurodegenerative therapeutic development.
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