通讯机构:
[Cheng, QZ ; Ding, H ] W;Wuhan Polytech Univ, Coll Med & Hlth Sci, 68 Xuefu South Rd, Wuhan 430023, Hubei, Peoples R China.;Wuhan Univ, Sch Pharmaceut Sci, 185 Donghu Rd, Wuhan 430072, Hubei, Peoples R China.
关键词:
Epilepsy;Luteolin;Neuronal apoptosis;Neuroinflammation;TLR4/I kappa B alpha/NF-kappa B pathway
摘要:
Epilepsy represents a prevalent neurological disorder in the population, and the existing antiepileptic drugs (AEDs) often fail to adequately control seizures. Inflammation is recognized as a pivotal factor in the pathophysiology of epilepsy. Luteolin, a natural flavonoid extract, possesses anti-inflammatory properties and exhibits promising neuroprotective activity. Nevertheless, the precise molecular mechanisms underlying the antiepileptic effects of luteolin remain elusive. In this study, we established a rat model of epilepsy using pentylenetetrazole (PTZ) to induce seizures. A series of behavioral experiments were conducted to assess behavioral abilities and cognitive function. Histological techniques, including HE staining, Nissl staining, and TUNEL staining, were employed to assess hippocampal neuronal damage. Additionally, Western blotting, RT-qPCR, and ELISA were utilized to analyze the expression levels of proteins involved in the TLR4/I kappa B alpha/NF-kappa B signaling pathway, transcription levels of apoptotic factors, and levels of inflammatory cytokines, respectively. Luteolin exhibited a dosedependent reduction in seizure severity, prolonged the latency period of seizures, and shortened seizure duration. Furthermore, luteolin prevented hippocampal neuronal damage in PTZ-induced epileptic rats and partially restored behavioral function and learning and memory abilities. Lastly, PTZ kindling activated the TLR4/I kappa B alpha/ NF-kappa B pathway, leading to elevated levels of the cytokines TNF-alpha, IL-6 and IL-1 beta, which were attenuated by luteolin. Luteolin exerted anticonvulsant and neuroprotective activities in the PTZ-induced epileptic model. Its mechanism was associated with the inhibition of the TLR4/I kappa B alpha/NF-kappa B pathway, alleviating the immuneinflammatory response in the post-epileptic hippocampus.
摘要:
<jats:p><jats:bold>Background:</jats:bold> Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine.</jats:p><jats:p><jats:bold>Methods:</jats:bold> FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug.</jats:p><jats:p><jats:bold>Results:</jats:bold> FSSO-loaded CS-AL NPs (212.1 ± 5.2nm, 45.1 ± 6.2mV) had a well-defined spherical shape with prolonged drug release and good storage within 4weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104mg/kg) group.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.</jats:p>
摘要:
Nowadays, an effective teaching platform is an important factor in the distance education. In the paper, the structure and functional modules of the teaching platform system based on web technology is studied comprehensively, and these functional modules of the teaching platform is introduced in detail. And the implementation process of the main technical and design principles is generated in the paper. The platform has some function of management and teaching in the education based on multi-layer structure.