Bosnian Journal of Basic Medical Sciences
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2018
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IF 1.432
Jing Chen,Guo Zheng,Hu Guo,Zhong-nan Shi,Jiao Jiang,Xiao-yu Wang,Xiao Yang,Xian-yu Liu
Status epilepticus (SE) is defined as continuous seizure activity lasting more than 5 minutes. It results in neuronal cell death, mediated by endoplasmic reticulum (ER) stress response. Previously, metformin demonstrated neuroprotective effects in primary cortical neurons. In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α)-C/EBP homologous protein (CHOP) pathway. SE was induced in rats by pentylenetetrazole. Following SE, the rats were treated with salubrinal, GSK2656157, or metformin. In a control group (normal saline) SE was not induced. CHOP, eIF2α, and PERK expression was determined by Western blot; apoptosis was analyzed by TUNEL assay. CHOP expression was significantly increased at 6 and 24 hours following SE. At both time points, eIF2α and PERK levels were also increased. At 6 hours, CHOP expression was significantly reduced in salubrinal, GSK2656157 and metformin groups versus SE group. eIF2α and PERK levels were decreased in metformin compared to SE group. eIF2α expression was markedly decreased in salubrinal versus SE group, while PERK expression was markedly reduced in GSK2656157 versus SE group. At 6 and 24 hours, the apoptosis rate was significantly increased in SE versus control group, while it was significantly reduced in salubrinal, GSK2656157, and metformin groups compared to SE group. The apoptosis rate also decreased in salubrinal group at 24 hours, although not to the extent observed in metformin group. Overall, CHOP expression and apoptosis induced by SE in rats were reduced with metformin. Further studies are required to evaluate the clinical relevance of metformin for patients with SE.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
MOLECULES
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2025
·Vol. 30
·期 16
·3400
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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
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有机合成
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DOI
PubMed
高影响因子
NEUROENDOCRINOLOGY
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2024
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IF 3.2
Zhang Jiaxian,Lai Wanlin,Tang Yusha,Gao Jing,Zhou Xiangyang,Chen Lei
Introduction:
In women of childbearing age with epilepsy, 40% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy. Methods:
A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. Susceptibility was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35. Results:
This study revealed that letrozole induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with anti-epileptic status in PCOS rats. Conclusion:
This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS
研究领域:
神经科学
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内分泌学
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癫痫研究
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生殖医学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2023
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IF 4.4
Zhang Shuai-nan,Li Hong-mei,Liu Qi,Li Xu-zhao,Yang Wu-de,Zhou Ying
Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy.
研究领域:
神经科学
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药理学
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分子生物学
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医学
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植物科学
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PubMed
高影响因子
NUTRITIONAL NEUROSCIENCE
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2025
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IF 3.6
Jiahao Liu,Jiawei Li,Yuanyuan Liu,Ruici Liu,Liya Fang,Zhimei Jiang,Lei Liu,Luchuan Wang,Chao Gong,Deming Kong,Ruting Fu,Pei Zeng,Jin Guo,Shaobo Zhou
Objective Epilepsy treatments often lead to vitamin D (VitD) deficiency. Although vitamin D₃ (VitD3) has been shown to reduce epileptic symptoms by 43%, its preventive effects remain unclear. This study investigated the potential of VitD pretreatment in two common acute epilepsy mouse models and explored its effects on seizure severity, latency, and molecular mechanisms involving calcium-sensing receptor (CaSR), phosphatase and tensin homolog (PTEN), and autophagy.Methods Mice were randomly divided into nine groups (n = 15). VitD or vehicle was administered 40 min before pentylenetetrazole (PTZ) or kainic acid (KA) given intraperitoneal injection (i.p). Seizure behavior and electroencephalograms (EEGs) were recorded for 60 min. After 24 h, hippocampal tissues were analyzed histologically and assessed for expression of autophagy-related proteins, CaSR, and PTEN.Results Both PTZ and KA induced acute seizures (Racine Grade IV+), with corresponding high-amplitude EEG spikes, neuronal damage, and mossy fiber sprouting. CaSR and autophagy markers were upregulated, while PTEN was downregulated, especially in the KA group. VitD pretreatment reduced seizure frequency, prolonged latency, alleviated hippocampal damage, downregulated CaSR and autophagy markers, and upregulated PTEN. These effects were milder than those of valproate. Combined VitD and Oroxin B treatment further improved outcomes.Conclusions (1) PTZ-induced seizures increased CaSR and decreased PTEN, triggering autophagy and worsening symptoms. (2) KA-induced epilepsy caused more severe damage with stronger autophagy activation. (3) VitD pretreatment mitigated seizures by modulating CaSR, PTEN, and autophagy, showing greater efficacy in the PTZ model.
研究领域:
神经病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 8.3
XiaoYang Qu,LiJuan Chen,JiangHua He,YuFei Fang,Jing Sun,ZhiYing Yu,Zhen Yang,ZiJing Zhang,JianBo Chen,Ling Dong
Background Epilepsy is a prevalent neurological disorder characterized by recurrent seizures and has limited effectiveness of available clinical treatments. Ferroptosis of neurons is one of the main mechanisms of epilepsy. Arisaema Cum Bile (ACB) is a traditional Chinese medicine that is prepared by fermenting animals bile with Rhizoma Arisaematis rhizomes, has demonstrated therapeutic effects on epilepsy and other nervous system diseases. Furthermore, the active components responsible for the anti-epileptic effects of ACB and the intrinsic mechanisms are still unclear. Purpose This study aims to clarify the principal bioactive constituents of ACB and their mechanisms in the treatment of epilepsy. It also seeks to provide data support for its clinical application in antiepileptic combination therapy. Method Pentylenetetrazol injections were used to induce epilepsy in rats. ACB and brain metabolites were identified via UPLC-Q-Exactive Orbitrap MS/MS, and active components were predicted through bioinformatics analysis. In vivo , ACB and hyodeoxycholic acid (HDCA) were administered by gavage, and the effects on oxidative stress, inflammation, and cognitive impairment were evaluated. Additionally, ferroptosis-related protein and gene expression were analyzed using western blot, PCR, immunofluorescence, and flow cytometry. In vitro , using primary neurons and HT22 cells, with electrophysiology employed to assess neuronal activity and glutamate used to induce ferroptosis in HT22 cells, in order to explore how HDCA alleviates epilepsy by inhibiting neuronal ferroptosis. Result A total of 37 chemical components were identified from the ACB, of which 10 active constituents can cross the blood-brain barrier, including steroids and terpenoids. Bioinformatics analysis suggests that HDCA may be one of the key active components responsible for ACB anti-epileptic effects and ferroptosis may represent a crucial underlying therapeutic mechanism. Studies in animals have demonstrated that treatment with ACB and HDCA reduced the frequency and severity of seizures in epileptic rats, mitigated hippocampal neuronal damage, improved post-epileptic cognitive learning capacity, alleviated neuroinflammatory injury and decreased markers of ferroptosis. This neuroprotective effect likely occurs through activation of the p53/Nrf2/GPX4 signaling pathway. Further in vitro cell experiments demonstrated that HDCA can inhibit the generation of action potentials in primary hippocampal neurons, protects HT22 neurons from glutamate-induced cell death, an effect that is reduced by Nrf2 inhibitors. These findings corroborate earlier bioinformatics analyses, confirming that the neuroprotective effects of HDCA are closely linked to Nrf2-mediated ferroptosis pathways. Conclusion HDCA is a key component of ACB anti-epileptic effects, potentially inhibiting ferroptosis through the p53/Nrf2/GPX4 pathway to reduce epilepsy.
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PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
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2025
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IF 3.7
Mi Wang,Tianqi Liu,Hao Wang,Zhenyuan Wang,Jiaheng Zhang
Graphical This study presents a sustainable supramolecular system composed of naturally derived ingredients: PE, AHP8, and a bioactive ionic liquid from betaine and MA, which offers multiple anti-aging benefits while promoting skin permeability. The growing demand for safe and sustainable cosmetics has led to a marked inclination toward natural extracts and peptides as raw materials. In this study, we developed a sustainable system with multiple antiaging effects by combining peony extract (PE) and acetyl hexapeptide-8 (AHP8) to simultaneously treat static and dynamic wrinkles, as well as skin dullness. As the poor skin permeability of AHP8 limited its efficacy, we used a bioactive ionic liquid derived from betaine and malic acid (MA) ([Bet][MA]) as a permeation enhancer. In vitro and in vivo zebrafish experiments indicated that [Bet][MA] not only significantly enhances transdermal and cellular penetration, but also exerts synergistic anti-aging effects. While being biosafe, [Bet][MA] significantly increased the transdermal permeation, skin retention, and cellular uptake of AHP8. Theoretical calculations revealed that [Bet][MA] improved the anti-wrinkle and whitening efficacies of AHP8 and PE through supramolecular interactions; it modulated their electron cloud distribution and molecular polarity and thus intensified their affinity to target proteins. The supramolecular PE/AHP8/[Bet][MA] system demonstrated excellent radical- and reactive oxygen species-scavenging capability, collagen production, and tissue repair capability while concurrently inhibiting tyrosinase activity, motion signaling, and inflammation. The study findings pave the way for sustainable and multifunctional skincare solutions.
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PubMed
高影响因子
Frontiers in Bioscience-Landmark
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2025
·Vol. 30
·期 6
·39587
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IF 3.1
Yongcheng Jiang,Lina Guo,Houde He,Haonan Chen,Tao Chen,Yan Liu,Wang Zhao
Background:Insomnia, the most prevalent sleep disorder, is clinically defined as difficulty initiating or maintaining sleep. Although many medications are effective for insomnia treatment, they carry risks of drug dependence and abuse. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signaling between the gastrointestinal tract and the central nervous system via gut microbes. Probiotics that provide mental and behavioral benefits through MGBA (psychobiotics) offer broad therapeutic potential. Methods:A non-toxic, drug-resistant strain of Lactobacillus reuteri E9 was isolated and characterized. Its effects were evaluated in a pentylenetetrazol (PTZ)-induced zebrafish model of sleep disorder. Neurotransmitter levels (glycine, serine, taurine, γ-aminobutyric acid (GABA)) and gene expression of GABA/melatonin receptors were analyzed.Results:E9 significantly upregulated inhibitory neurotransmitters, including GABA, taurine, glycine, and serine (p < 0.05). In PTZ-induced zebrafish, E9 exerted sedative effects by reducing seizures and hyperactivity. Concurrently, E9 upregulated the expression of GABA receptor genes and melatonin receptor (Mtnr1aa) genes in zebrafish neural tissue.Conclusions:Lactobacillus reuteri E9 demonstrates potential as a psychobiotic for sleep disorder management by modulating key inhibitory neurotransmitters and sleep-related receptor expression via the MGBA pathway, offering a non-pharmacological alternative to conventional treatments.
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高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
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2025
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IF 3.9
Qingquan Guo,Yudong Zhang,Jianhua Zhang,Xiaoyu Tian,Yawen Zhou,Yaxin Wang,Mingjie He,Lu Chen,Jiaqi Zeng,Chuanjin Tang,Qiuru Li,Zhenming He,Bingji Ma,Chenyang Jiang,Haishan Zhao
Melanin-Concentrating Hormone (MCH) is a cyclic peptide initially isolated from salmon and later found to be conserved in mammals. It plays a role in regulating melanin changes and rhythmic behaviors such as sleep and feeding, though its relationship with these processes is not fully understood. Our preliminary research revealed significant differences in melanin degradation in zebrafish under varying light conditions, suggesting a link to MCH. This study aims to explore MCH's role in lighting-induced changes in rhythmic behavior patterns and melanin of zebrafish. Using the zebrafish model, we evaluated MCH expression under different lighting conditions and analyzed the effects of arousal-promoting and sleep-inducing agents. We also investigated the impact of exogenous MCH and its inhibitors on melanin degradation, behavioral changes, and differences in MCH expression to uncover potential regulatory relationships between MCH, sleep pressure, and melanin. In-depth research using flow cytometry, AO staining, Lyso-Tracker Red staining, and RT-qPCR analysis of autophagy- and apoptosis-related genes showed that melanin degradation regulation depends on MCH expression levels. Sleep pressure can intervene in MCH's effects, forming a regulatory loop to jointly regulates melanin degradation. The influence of the MCH-sleep pressure loop on melanin degradation is closely tied to autophagic and lysosomal pathways. Our findings reveal a mutually regulatory loop in zebrafish between MCH and sleep pressure, affecting melanin degradation through these pathways.
研究领域:
神经生物学
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细胞生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Tan Xue,Qi Wang,Panpan Zhang,Yan Miao,Jianing Sun,Fengyu Dong,Xinjing Gui,Jing Yao,Ruixin Liu
This study investigates the consistency between the formula granule decoction of stir-fried Bombyx Batryticatus(JC-DGD) and its traditional decoction (JC-TD) counterpart, using roasted Bombyx Batryticatus as a representative example.First, used high-performance liquid chromatography (HPLC) to establish the fingerprints of JC-TD and JC-DGD from four manufacturers (A, B, C, and D) and assess their similarity. There was no significant difference between the two ( P > 0.05).Quantified five key index components, including uracil.Compared the protein and crude polysaccharide contents using the Coomassie Brilliant Blue and phenol-sulfuric acid methods. The mean total content of index components, proteins, and crude polysaccharides in 10 batches of JC-TD was set as 1. The contents of index components in different categories - JC-DGD-provincial standard(JC-DGD-PS), JC-DGD-enterprise standard(JC-DGD-ES), TD, DGD, and DGCM from manufacturers A, B, C, and D—were 1.23, 0.38, 1.00, 0.72, 1.28, 0.58, 0.45, and 0.27, respectively. The protein contents were 1.51, 0.46, 1.00, 0.88, 1.43, 0.93, 0.35, and 0.66, respectively. The crude polysaccharide contents was 9.01, 0.74, 1.00, 4.05, 10.57, 1.96, 0.38, and 1.77, respectively. We identified 32 differential volatile organic compounds, including fenugreek lactone, using GC-IMS. Then evaluated the anticonvulsant effects of JC-TD and JC-DGD using an acute convulsion mouse model induced by pentylenetetrazole. The results showed that JC-DGD-A > JC-TD ≈ JC-DGD-B ( P > 0.05)) were superior to those of JC-DGD-C and JC-DGD-D ( P < 0.01). Finally, calculate the recommended equivalent ratio of Chinese medicine formula granules (DGCM). The manufacturers A, B, C, and D were adjusted from 1:3, 1:10, 1:10, and 1:11–1:4.54 ± 0.51, 1:5.24 ± 2.22 (JC-B3 without adjustment: 1:3.6), 1:5.17 ± 0.49, and 1:3.44 ± 0.59, respectively. The overall, and the consistency between the two was analyzed through correlation analysis, cluster analysis, and multi-index dimensionality reduction discriminant analysis.Comprehensive results indicated that the quality of JC-DGD-A was significantly higher than that of JC-TD, while JC-DGD-B exhibited similar quality to JC-TD. In contrast, the quality of JC-DGD-C and JC-DGD-D was significantly lower than that of JC-TD. To enhance product quality and ensure the scientific rationality of clinical applications, manufacturers must adhere to national and provincial standards for formula granule drugs.
研究领域:
中药学
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分析化学
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药理学
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DOI
PubMed
高影响因子
Biology-Basel
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2025
·Vol. 14
·期 5
·488
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IF 3.5
Liang Chen,Jiaxin Li,Wenhui Zhang,Jiepeng Wang
Simple SummaryAcorus tatarinowiiSchott (ATS) is a plant-based medicine that has been used historically to manage epilepsy, but its exact mechanisms are still not fully understood. This lack of clarity limits its use in clinical treatments. To explore how ATS might help prevent epilepsy, we used a rat model with chronic epilepsy induced by pentylenetetrazole (PTZ). We analyzed the brain’s chemical makeup using a technique called UPLC/MS and identified key differences with statistical methods like PCA and OPLS-DA. We also looked at the gut bacteria using 16S rRNA sequencing. Our results showed that giving ATS orally (50 mg/kg) significantly improved seizure latency and pathology in epileptic rats. Important factors included changes in ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and gut flora. These findings provide a foundation for further research into ATS’s potential as an epilepsy treatment.As a phytotherapeutic agent with historical applications in epilepsy management,Acorus tatarinowiiSchott (ATS) remains pharmacologically enigmatic, particularly regarding its pathophysiological mechanisms. This knowledge gap significantly hinders the clinical application of ATS-based treatments. To explore the potential of ATS in combating epileptogenesis, we utilized a pentylenetetrazole (PTZ)-induced chronic epilepsy rat model. Brain metabolomic analysis was performed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS). Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were performed for screening differential metabolites. Gut microbiota composition was analyzed through 16S rRNA gene sequencing and examined using Spearman correlation analysis. The results show that oral ATS (50 mg/kg) significantly improved the seizure latency and pathology of rats with epilepsy. Ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and intestinal flora were crucial for ATS’s ability to counteract epilepsy. The therapeutic effects of ATS against epilepsy were investigated with brain metabolomics and gut microbiota analysis, providing the basis for further comprehensive research.
研究领域:
神经科学
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药理学
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代谢组学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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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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PubMed
高影响因子
危险品化学品经营许可证（带存储）