JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2022
·
IF 3.571
Jing Jiang,Zhao-liang Hu,Hamza Boucetta,Jia-ming Liu,Min Song,Tai-jun Hang,Yu-ting Lu
Flumazenil is an imidazobenzodiazepine derivative that antagonizes the actions of benzodiazepines . The degradation pathway elucidation plays an important role in the drug quality control. In this work, a reliable LC-Q-TOF/MS method was developed to separate and identify the degradation products of flumazenil generated in the stress testing conducted according to the ICH Q1A(R2) guideline. Fifteen degradation products were detected in total including three reported impurities and twelve unknown impurities. Based on the chromatographic and mass spectrometric data acquired, the structures of all the degradation products were identified. Besides, two major degradants were synthetized and further confirmed by NMR. The degradation pathways of flumazenil were elucidated, and the degradation characteristics of benzodiazepines were also discussed. The obtained results are of both great importance for the quality control of flumazenil and good reference for the degradation study of other benzodiazepines.
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高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4702
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IF 3.267
Nan Zhang,Mu Luo,Lei He,Lei Yao
Gardenia jasminoidesEllis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of ‘Shanzhizi’, which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation ofG. jasminoidesessential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation ofG. jasminoidesessential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.Keywords:Gardenia jasminoides;essential oil;inhalation;anxiolytic effect;serotonergic neurotransmission
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JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2019
·
IF 2.439
Kai Zhang,Jing Lu,Lei Yao
Cedrol, mainly derived from Juniperus virginiana L. essential oil, has been demonstrated the anxiolytic effect, although its mechanism of action is still not fully established. In the present study, male ICR mice were submitted to the elevated plus maze (EPM) and light–dark box (LDB) tests to investigate the putative mechanism of anxiolytic effect. WAY100635 (5-HT 1A receptor antagonist), flumazenil (benzodiazepine receptor antagonist), SCH23390 (dopamine D 1 receptor antagonist) or sulpiride (dopamine D 2 /D 3 receptor antagonist) were used in the behavioral experiment to determine the mechanism of action of cedrol. Subsequently, the monoamine neurotransmitter levels were evaluated after behavioral tests. The data suggest that no significant effect in behavioral parameters were observed after sole intraperitoneal (i.p.) injection of antagonists compared to saline group. The anxiolytic effect of cedrol in behavioral procedures was blocked by either WAY100635 or flumazenil. The anxiolytic effect of cedrol (1200 mg/kg) was effectively antagonized by SCH23390 (0.125 mg/kg). Furthermore, cedrol decreased the DA and NE levels in hippocampus, striatum and hypothalamus. The present findings suggest that the dopaminergic system (D 1 receptor) rather than serotoninergic or GABAergic system may potentially be involved in the modulation of cedrol-induced anxiolytic-like behaviors in mice.
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Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Niping Li,Yaorong Yang,Shengyuan Zhang,Bin Jiang,Wei Zhang,Haibo Wang,Lixin Chen,Liwei Wang,Yiyi Li,Lei Shi,Wencai Ye,Lei Wang
Gelsemium elegans ( G. elegans ) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans , resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure–toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine ( 1 ), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine ( 1 ) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA A receptor antagonists successively reversed action potential firing in gelsenicine ( 1 )-treated VRG neurons. Importantly, the GABA A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.
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