INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2013
·Vol. 14
·期 12
·23751-23761
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IF 2.464
Jun Xiang,Yugang Jiang
Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAAand GABABin the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAAin the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.Keywords:antiepileptic;matrine;gamma-aminobutyric acid;glutamic acid
研究领域:
药理学
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神经科学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2015
·Vol. 172
·期 16
·4052-4065
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IF 4.842
Lin Guo,Yanke Chen,Rui Zhao,Guanghui Wang,Eitan Friedman,Ao Zhang,Xuechu Zhen
Background and Purpose Application of orthosteric sigma-1 receptor agonists as anti-seizure drugs has been hindered by questionable efficacy and potential adverse effects. Here, we have investigated the anti-seizure effects of the novel and potent allosteric modulator of sigma-1 receptors, SKF83959 and its derivative SOMCL-668 (3-methyl-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol). Experimental Approach The anti-seizure effects of SKF83959 were investigated in three mouse models, maximal electroshock seizures, pentylenetetrazole-induced convulsions and kainic acid-induced ‘status epilepticus’. Also, in rats, the cortical epileptiform activity induced by topical application of picrotoxin was recorded in electrocorticograms. In rat hippocampal brain slices, effects of the drugs on the high potassium-evoked epileptiform local field potentials were studied. Anti-seizure activities of SOMCL-668, a newly developed sigma-1 receptor selective allosteric modulator, were also investigated. Key Results SKF83959 (20, 40 mg·kg −1 ) exhibited anti –seizure actitity in the three mouse models and reduced the cortical epileptiform activity without alteration of spontaneous motor activity and motor coordination. These effects were blocked by the sigma-1 receptor antagonist BD1047, but not the dopamine D 1 receptor antagonist SCH23390. SKF83959 alone did not directly inhibit the epileptiform firing of CA3 neurons induced by high potassium in hippocampal slices, but did potentiate inhibition by the orthosteric sigma-1 receptor agonist SKF10047. Lastly, a selective sigma-1 receptor allosteric modulator SOMCL-668, which does not bind to dopamine receptors, exerted similar anti-seizure activities. Conclusions and Implications SKF83959 and SOMCL-668 displayed anti-seizure activities, indicating that allosteric modulation of sigma-1 receptors may provide a novel approach for discovering new anti-seizure drugs.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 17
·10460-10466
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IF 4.036
Zhichao Jin,Chunhua Yan,Huimin Chu,Qing Huang,Zhizhong Wang
Among the cyclodextrins screened for the synthesis of 2-hydroxy-1,2-diphenylethanone (benzoin) in water, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) exhibited the highest yield in the benzoin condensation reactions, and HP-β-CD can be recycled several times with little loss of activity through the addition of fresh VB1. As an example of supramolecular catalysis, the methodology was applied to the “green” synthesis of the antiepileptic drug phenytoin through benzoin condensation, oxidation, and cyclization reactions in the presence of HP-β-CD, without the use of any harmful organic solvent. Moreover, the complexation behaviors of HP-β-CD with benzaldehyde and intermediates were studied by UV-vis and 2D-ROESY NMR spectroscopies to reveal the plausible mechanisms of the reactions, and HP-β-CD did not act as a simple phase transfer agent.
研究领域:
有机化学
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药物化学
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绿色化学
✓ 已验证
DOI
高影响因子
TALANTA
·
2024
·
IF 5.6
Chun-Ying Xu,Yi-Xin Zhong,Yuan-Yuan Cui,Cheng-Xiong Yang
Owing to their incomplete digestion in the human body and inadequate removal by sewage treatment plants, antiepileptic drugs (AEDs) accumulate in water bodies, potentially affecting the exposed humans and aquatic organisms . Therefore, sensitive and reliable detection methods must be urgently developed for monitoring trace AEDs in environmental water samples. Herein, a novel phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network (Fe 3 O 4 @CD-MON-PBA) was designed and synthesized via the thiol-yne click post-modification strategy for selective and efficient magnetic solid-phase extraction (MSPE) of trace AEDs from complex sample matrices through the specific B–N coordination, π-π, hydrogen bonding , electrostatic, and host-guest interactions. Fe 3 O 4 @CD-MON-PBA exhibited a large surface area (118.5 m 2 g −1 ), rapid magnetic responsiveness (38.6 emu g −1 , 15 s), good stability and reusability (at least 8 times), and abundant binding sites for AEDs. Under optimal extraction conditions, the proposed Fe 3 O 4 @CD-MON-PBA-MSPE-HPLC-UV method exhibited a wide linear range (0.5–1000 μg L −1 ), low limits of detection (0.1–0.5 μg L −1 ) and quantitation (0.3–2 μg L −1 ), good anti-interference ability, and large enrichment factors (92.2–104.3 to 92.3–98.0) for four typical AEDs. This work confirmed the feasibility of the thiol-yne click post-synthesis strategy for constructing novel and efficient multifunctional magnetic CD-MONs for sample pretreatment and elucidated the significance of B–N coordination between PBA and N-containing AEDs.
研究领域:
环境科学
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分析化学
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药学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
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2025
·
IF 2.6
Xiao-han Peng,Fan Zhang,Xin-feng Xia,Kun Wang,Yan-Lin Zhao,Yan Du,Daoquan Tang
Pharmacological treatment with antiepileptic drugs (AEDs) remains a primary selection for most patients with epilepsy, while therapeutic drug monitoring is an important strategy to ensure the efficacy and safety of AEDs. The aim of this study was to optimize and develop a green high-performance liquid chromatography (HPLC) method suitable for simultaneous detection of 8 AEDs and 2 active metabolites including primidone (PRM), lamotrigine (LTG), carbamazepine (CBZ) and its active metabolite 10,11-epoxide (CBZE), oxcarbazepine (OXC) and its active metabolite 10, 11-dihydro-10-hydroxyl carbamazepine (MHD), phenobarbital (PHB), eslicarbazepine acetate (ESLA), clonazepam (CZP) and diazepam (DZP) in human serum. The results showed that using chlorzoxazone as the internal standard, ethanol as protein precipitant of serum, ZORBAX Eclipse Plus-C18 (150 × 4.6 mm, 3.5 μm) column as stationary phase, and gradient ethanol and 15 mM potassium dihydrogen phosphate water solution as green alternative mobile phase, good chromatographic separation for 10 target analytes could be obtained. The calibration curves of 10 analytes demonstrated good linearity within the test range (r > 0.996). The intra- and inter-batch precision and accuracy were all less than 15%, while extraction recoveries were in the range of 74.57-90.89 % with the relative standard deviation values less than 15%. The results of greenness assessment showed that the proposed method was ecofriendly. Finally, the validated method was successfully applied in the determination of real serum samples.
研究领域:
药理学
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分析化学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhou Haidong,Ying Tianqi,Wang Xuelian,Liu Jianbo
Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics and lipid regulators were analysed and detected in water samples collected from 18 sampling sections along the three main urban rivers in Yangpu District of Shanghai, China during four sampling campaigns. Besides, algal growth inhibition test was conducted to preliminarily assess the eco-toxicology induced by the target pharmaceuticals in the rivers. Mean levels for most of target compounds were generally below 100 ng/L at sampling sections, with the exception of caffeine and paracetamol presenting considerably high concentration. The detected pharmaceuticals in the urban rivers ranged from
研究领域:
环境科学
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毒理学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
·
IF 3.1
Xiao-han Peng,Yan-lin Zhao,Zhong Huang,Xin-feng Xia,Kun Wang,Peng Jin,Yan Du,Dao-quan Tang
Currently, treatment with antiepileptic drugs (AEDs) is still the first choice for epileptic patients, while monitoring their blood concentrations is undoubtedly beneficial for minimizing their adverse side effects and optimizing their therapeutic effects. In this study, an ultra-high performance liquid chromatography coupled with tandem mass spectrometry with polarity switching was developed and validated for simultaneous determination of 14 AEDs and 2 active metabolites in human serum. Olanzapine was selected as the internal standard. One-step protein precipitation using methanol containing 0.05 % formic acid was used to treat sample, and the supernatant was injected for analysis without further evaporation and reconstitution. Chromatographic separation was performed on an Aglient Zorbax Eclipse Plus C18 (50 mm × 2.1 mm, 1.8 μm) column with gradient methanol and 0.1 % formic acid in water as mobile phase. Multi-reaction monitoring was performed for quantification of 16 analytes in polarity switching mode. Matrix-matched calibration curves of 16 analytes presented good linearity within the test concentration range ( r > 0.99). The intra- and inter-run accuracies and precisions at the lower limit of quantification, and low, medium and high quality control levels were all less than 20 % or 15 %, respectively. The extraction recovery, matrix effect, and stability were all acceptable under detected conditions. Finally, this method was successfully applied in the quantitation of target analytes in the serum of patients received AEDs.
研究领域:
药理学
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临床医学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Zhen Zou,Xiaodou Liao,Le Yang,Ziyun Huang,Hua Yang,Qi Yan,Yufei Zhang,Zhihe Qing,Lihua Zhang,Feng Feng,Ronghua Yang
Tiagabine hydrochloride (TGB) is a clinically frequently used drug for anticonvulsion and reducing epileptic frequency. Over administration of TGB could bring about adverse effects, such as speech disorder, depression, and even suicidal tendencies. Therefore, accessible and sensitive assay for analysis of TGB becomes an urgent need toward guiding clinical medication. Here, we present the first report on fluorescence turn-on detection of TGB in urine testing. In this protocol, a fluorescent dye, perylene tetracarboxylic acid imide derivative (PTAI), is found specifically occupying the Sudlow site II of human serum albumin (HSA) and displays a new phenomenon of binding-induced quenching (BIQ). In presence of TGB, competitive binding of the TGB to the site II of HSA will trigger release of PTAI, thus successfully lighting up the fluorescence of PTAI. This label-free assay enjoys a broader working range (1–350 μM) and lower detection limit (0.218 μM) than the traditional liquid chromatography method and is uninterfered by the miscellaneous in the artificial urine. The BIQ probe highlights the merits of HSA as a quencher and a molecular recognition unit, and it opens up a way for studying drug-HSA interaction mechanism and noninvasive pharmaceutical testing.
研究领域:
生物化学
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医学检测
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药物分析
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2022
·
IF 6.911
Wei Hu,Wei Zhou,Chenlu Wang,Zichun Liu,Zilin Chen
Development of high-throughput and rapid screening analytical method is in high demand for anti-doping and clinical point-of-care (POC) analysis. Solid-phase microextraction and mass spectrometry direct coupling (SPME-MS) has been proved as a rapid and effective way for target analysis in complex sample matrixes. An online direct coupling of in-tube SPME (IT-SPME) with MS using polymer coated open-tubular column has been developed in this work. A sharp stainless-steel needle was attached at the end of the SPME column, which enables the direct ionization of the analytes after elution from the IT-SPME column. Itaconic acid-benzene co-polymer was in-situ grown on the inner surface of the fused silica capillary and used as extraction phase. This column has low backpressure and provides both hydrophobic and weak cationic exchange interaction with the target analytes due to the chemical properties. The developed online IT-SPME-MS method showed good extraction performance towards various target analytes and good reusability at least for 60 times. As a proof-of-concept application, the above method was applied for the analysis of antiepileptic drugs (AEDs) in both plasma and urine samples with linear range (1 ng/mL-200 ng/mL), good linearity (R 2 ≥ 0.99), and good reproducibility (intra-day RSDs less than 4.36%, inter-day RSDs less than 6.55%). The method exhibited high enrichment factors between 187 and 204 for the two AEDs and high sensitivity for the analysis of human plasma samples and urine samples.
研究领域:
分析化学
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临床医学
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药物分析
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2024
·
IF 3.8
Qing Wang,Xinyu Shi,Shao-Feng Tang,Huanhuan Wang,Yuan Chen,Na Zhang
Simultaneous monitoring of plasma concentration levels of multiple antiepileptic drugs (AEDs) is essential for dose adjustment in comprehensive epilepsy treatment, necessitating a sensitive technique for accurate extraction and determination of AEDs. Herein, a magnetic solid-phase extraction (MSPE) technique on the basis of modified biochar (BC) is investigated to extract four AEDs from plasma, in conjunction with high performance liquid chromatography. BC derived from Zizyphus jujuba seed shells was activated by phosphoric acid (PBC) and magnetized via coprecipitation to produce MPBC. The MPBC-CD obtained after modification with β-cyclodextrin (CD) was characterized and evaluated for adsorption. It exhibited fast adsorption kinetics based on second-order kinetics and satisfactory adsorption capacity for AEDs. Then it was employed as the MSPE adsorbent and the influencing parameters were optimized. The enrichment factor was 18.75. The validation analysis revealed a favorable linearity that ranged from 0.04 to 20 μg·mL −1 along with a low limit of detection of 6.85 to 10.19 ng·mL −1 . The recovery of the AEDs ranged from 78.7 to 109.2%, with relative standard deviations below 6.7%. Using quantum chemistry theory calculations and experimental results analysis, the adsorption mechanism was investigated. It disclosed that the suggested strategy built upon MPBC-CD was appropriate for the assessment of AEDs in plasma and expanded the usage of BC as the environmentally favorable matrix for the analysis of biological samples.
研究领域:
分析化学
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
MARINE BIOTECHNOLOGY
·
2025
·Vol. 27
·期 3
·1-9
·
IF 2.8
Li Jinling,Zhou Zhiyan,Feng Fangjian,Yuan Wei,Zhang Yawen,Wang Jiaxing,Zhang Bin,Jin Haixiao,He Shan,Ding Lijian
Epilepsy is a serious brain disease that urgently needs new drugs to treat it. In this study, three new α -pyrone derivatives, nocardipones A − C ( 1 − 3 ), were isolated from the sponge-associated actinomycete Nocardiopsis sp. NBUDK19 guided by anti-epileptic bioactivity using an in vivo zebrafish model. Compounds 1 − 3 were isolated and purified by silica gel column chromatography combined with semi-preparative HPLC. The structures of 1 − 3 were elucidated by UV, HRESIMS, NMR spectroscopic analysis, optical rotation, and computational chemical calculations. Our pharmacological study showed that compounds 1 − 3 exhibited notable reductions in seizure-like locomotor activity at 5 μg/mL. The qPCR analysis showed that compounds 1 − 3 significantly regulated the mRNA expression levels of c-fos and genes associated with GABAergic-glutamatergic signaling, including gria1b and gat1 . The molecular docking revealed that compounds 1 − 3 strongly binding to 4-aminobutyric acid transaminase, with binding energies of − 7.3, − 7.8, and − 7.3 kcal/mol, respectively. This work enriches bioactive drug discovery to treat epilepsy and illustrates an underlying pharmacological and molecular mechanism of these natural α -pyrones.
研究领域:
药理学
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海洋微生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2017
·
IF 3.981
Jingyi Zhang,Donghao Liu,Xiaoyan Meng,Yi Shi,Ruya Wang,Deli Xiao,Hua He
In this study, a novel solid phase extraction based on porous magnetic graphene oxide-cyclodextrin polymers (MGO-CD) was developed with aromatic linker and used for the simultaneous extraction and preconcentration of trace antiepileptic drugs in plasma. The characteristics of MGO-CD were assessed by Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller surface areas (BET), Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). Magnetic cyclodextrin polymeric material exhibited a high specific surface area (187 m 2 g −1 ), large pore volume (0.12 cm 3 g −1 ), good saturated magnetization (37.68 emu g −1 ), and excellent dispersibility in aqueous solution. Various parameters influencing the extraction recovery of drugs were studied. The method exhibited good linearity in the range of 1–50 μg mL −1 , and the limit of quantitation of carbamazepine, phenytoin, diazepam was 11.89, 47.10 and 16.17 ng mL −1 , respectively. The recoveries of three antiepileptic drugs range from 78.49 to 100.93% with relative standard deviations less than 5.5%. These analytical results demonstrated that the proposed approach based on MGO-CD was applicable for analysis of antiepileptic drugs in plasma samples.
研究领域:
分析化学
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药物分析
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）