JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2024
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IF 2.5
Peipei Feng,Jingyi Chen,Xiaolu Chen,Minghui Tang,Ni Song,Lanyue Zhang,Tinggang He
Delayed treatment of insomnia-related symptoms can harm physical health and increase the psychological burden. In addition to oral medications and some physical therapies, aromatherapy can help overcome some treatment-related side effects. Herein, parachlorophenylalanine (PCPA)-induced insomnia was established in Kunming (KM) mice, which were subjected to aromatherapy using five plants ( Jasminum sambac , Magnolia denudata , Rosa rugosa , Aloysia citriodora , and Abies balsamea ) essential oils (EOs). To determine the sleep-inducing effect of the five EOs, the rate of change in body weight, sleep latency, and total sleep time in mice were measured. Specific serum indices were used to evaluate the therapeutic effects of the tested drugs and PCPA modeling. Gas chromatography-mass spectrometry (GC-MS) was employed to identify active components in EOs. The five EOs contained multiple identical constituents and were rich in terpenoids, such as α-farnesene (28.42%), linalool (68.84%), and citronellol (23.78%). The EOs exhibiting varying effects on insomnia-induced weight loss. Nissl staining was used to examine and the number of neurons was elevated in the EO-treated groups when compared with the PCPA-induced group; however, the neuronal number was reduced in the hypothalamic tissues of the R. rugosa EO (RREO)-treated group. All EOs upregulated the expression of 5-HT1A and GABA A Rα1, as demonstrated by immunohistochemistry, western blotting, and reverse transcription-quantitative PCR results. In addition, EOs of A. citriodora and A. balsamea significantly upregulated the expression of 5HT 1A protein, whereas EOs of J. sambac and M. denudata exerted significantly different effects when compared with the model group, as determined by western blotting.
研究领域:
神经科学
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药理学
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植物化学
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DOI
PubMed
高影响因子
TALANTA
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2020
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IF 5.339
Xia Wang,Xiuzhu Huo,Ran Yang,Zhaohui Li,Yuanqiang Sun,Lingbo Qu,Huajin Zeng
Long and real time imaging of cell membrane is very important for better understanding of cell performances in physiological and pathological processes. Nowadays, fluorescence probe analysis has become an indispensable tool for monitoring cell membrane. Herein, a novel fluorescent probe based on specific recognition of GABA A receptor was developed for imaging cell membrane. The probe synthesized in this work has been successfully applied to image different kinds of cell membrane with some advantages over the reported probes. Moreover, the probe also showed good superiority in the preliminary screening GABA A drugs.
研究领域:
细胞生物学
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
Scientific Reports
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2014
·Vol. 4
·期 1
·1-5
·
IF 5.078
Zhu Qing,Sun Yuehua,Zhu Jie,Fang Tian,Zhang Wei,Li Jun-Xu
Sinomenine is a principal ingredient of traditional Chinese medicine, Sinomenium Acutum , which has been reported to have various pharmacological effects including anti-rheumatism and immunomodulation. This study examined the effects of sinomenine in rats that received chronic constriction injury (CCI), a model of peripheral neuropathic pain. CCI injury on the right sciatic nerve led to long-lasting mechanical hyperalgesia. Acute sinomenine treatment (10–40 mg/kg, i.p.) significantly and dose-dependently reversed mechanical hyperalgesia. In addition, the antinociceptive effects of sinomenine remained stable during repeated daily treatment for up to 2 weeks. Although sinomenine did not alter the duration of immobility in the forced swimming test in healthy animals, it dose-dependently reversed the increased immobility time in rats receiving CCI, suggesting that sinomenine attenuated chronic pain-induced depressive-like behavior. The antinociceptive effects of sinomenine were blocked by the GABAa receptor antagonist bicuculine. The doses of sinomenine studied here did not significantly alter the spontaneous locomotor activity. Together, these results suggested that sinomenine exerts significant antinociceptive effects for neuropathic pain via GABAa-mediated mechanism, which suggests that sinomenine may be useful for the management of chronic painful conditions such as neuropathic pain.
研究领域:
药理学
·
疼痛研究
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神经科学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Shiben Wang,Hui Liu,Kang Lei,Guangyong Li,Jun Li,Yuyu Wei,Xuekun Wang,Renmin Liu
In this study, a series of 3,4-dihydroquinolin-2(1 H )-one derivatives were designed and synthesized using two experimental models, namely maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ), to test the anticonvulsant activity of the target compound in vivo (i.p. in Kunming mice). The neurotoxicity (NT) of the target compound was measured by the rotating rod method (i.p. in Kunming mice). Six compounds with potential activity were selected from the two experimental models to test the 50% effective dose (ED 50 ). In vitro binding experiments with the GABA A receptor were also performed. The results of the pharmacological experiments showed that compound 7-((5-(pentylthio)-1,3,4-oxadiazol-2-yl)methoxy)-3,4-dihydroquinolin-2(1 H )-one ( 5b ) showed the best anticonvulsant activity (MES, ED 50 = 10.1 mg/kg; scPTZ, ED 50 = 9.3 mg/kg), which was superior to activities shown by carbamazepine and ethosuximide, and it also exhibited the most potent binding affinity to GABA A receptors (IC 50 = 0.12 μM). The GABA content in Wistar rat brains (i.p.) was also investigated, and the results showed that compound 5b may have a certain effect on the GABA system, as it increased the GABA concentration in the brain of rats. Molecular docking was used to study the binding mode of compound 5b and the GABA A receptor. Compound 5b showed significant interactions with residues at the benzodiazepines binding site on the GABA A receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.0.
研究领域:
药理学
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神经科学
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药物化学
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DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2025
·
IF 3.9
Ying Sun,Yajun Bai,Bin Li,Peinan Fan,Haiyan Lu,Pu Jia,Ye Zhao,Yujun Bai,Shixiang Wang,Kechun Liu,Meng Jin,Tai-Ping Fan,Xiaohui Zheng
Developmental epileptic encephalopathies (DEEs), including Dravet syndrome (DS), require antiseizure medications (ASMs) that balance efficacy with developmental safety. There is an urgent clinical need for novel therapeutic agents that combine potent anticonvulsant activity with developmental safety. β-Asarone, an active constituent of Acorus plants, has demonstrated antiepileptic potential, but its toxicities severely limit clinical application. Notably, β-asaronol, a hydroxylated metabolite of β-asarone, may exhibit improved safety; however, its pharmacological properties and therapeutic potential remain systematically unelucidated. To evaluate the developmental safety and antiseizure efficacy of β-asaronol for pediatric refractory epilepsy, developmental toxicity, antiseizure activity, and neuroprotective effects were systematically assessed using zebrafish models (Tg vmat2:GFP, Tg lfabp:EGFP, pentylenetetrazole (PTZ)-induced seizures, and scn1lab–/– mutants). Electrophysiology, molecular docking, and biomarker analyses elucidated mechanisms. β-Asaronol (5–150 μM) exhibited no significant developmental toxicity in zebrafish, with normal hatching rate, mortality, malformation rate, and no abnormalities in neurotoxicity or hepatotoxicity indicators. Its lethal concentration 50 (LC50) value was 3.5-fold higher than that of the parent compound β-asarone. It prolonged seizure latency, suppressed PTZ-induced hyperactivity (150 μM restoring baseline locomotion), and reduced neuronal apoptosis (lactate dehydrogenase (LDH)/c-fos normalization). In scn1lab–/– mutants, β-asaronol outperformed stiripentol and cannabidiol, reducing epileptiform discharges by about 93%. Mechanistically, β-asaronol potentiated γ-aminobutyric acid type A (GABAA) receptor currents (EC50 = 20.8 μM) via benzodiazepine-binding site interactions. β-Asaronol combines superior developmental safety with potent antiseizure efficacy, positioning it as a promising candidate for Dravet syndrome and refractory epilepsy.
研究领域:
神经药理学
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发育毒理学
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癫痫研究
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民族药理学
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分子模拟
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神经科学
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DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 16
·3400
·
IF 4.6
Lina Hu,Mengjiao Li,Zheng Liu,Hui Yan,Xuekun Wang,Shiben Wang
To discover novel, potent anticonvulsant compounds, a series of compounds containing triazole structural fragments were synthesized and evaluated for their anticonvulsant activity. Compounds6f(maximal electroshock (MES), 50% effective dose (ED50) = 13.1 mg/kg; subcutaneous pentylenetetrazole (scPTZ), ED50= 19.7 mg/kg) and6l(MES, ED50= 9.1 mg/kg;scPTZ, ED50= 19.0 mg/kg) showed the best activity in MES andscPTZ tests. The results of an affinity test showed that the potent compounds had better binding to the GABAAreceptors. The results of an inhibitory neurotransmitter GABA content test in brain tissue indicated that compounds6fand6lexerted anticonvulsant activity which may be associated with the increase of GABA content in the rat brain. Elevated plus maze (EPM) assay results showed that compounds6fand6lpossessed anxiolytic effects, and their effects correlated with the binding sites of benzodiazepines (BZs) in the GABAAreceptors. Molecular docking was performed to investigate the interactions of the studied compound6lwith the GABAAreceptors on the molecular level.
研究领域:
药物化学
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药理学
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神经科学
·
有机合成
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2015
·Vol. 29
·期 7
·996-1003
·
IF 2.66
Hao Liu,Zhi Song,Da-Guang Liao,Tian-Yi Zhang,Feng Liu,Kai Zhuang,Kui Luo,Liang Yang,Jing He,Jian-Ping Lei
This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii . The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABA A , Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up-regulation of GABA A and GAD65 expressions, and anti-apoptosis of neuron the in brain. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
药理学
·
神经科学
·
生物化学
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DOI
PubMed
高影响因子
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