Palmatine attenuates LPS‐induced neuroinflammation through the PI3K/Akt/NF‐κB pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2023, Volume and Issue: 38(1)

Published: Oct. 10, 2023

Abstract To investigate the key molecular mechanisms of palmatine for treatment neuroinflammation through modulation a pathway using docking, dynamics (MD) simulation combined with network pharmacology, and animal experiments. Five alkaloid components were obtained from traditional Chinese medicine Huangteng literature mining. Molecular docking MD acetylcholinesterase used to screen palmatine. At level, mice injected LPS intracerebrally cause neuroinflammatory model, Morris water maze experiment was performed examine learning memory mice. Anxiety levels tested autonomous activity behavior open field elevated HE staining Niss on brain tissue sections observe morphological lesions apoptosis; serum examined inflammatory factors TNF‐α, IL‐6, IL‐1β; Western blot detect protein expression. The expression PI3K/AKT/NFkB signaling pathway‐related proteins by blot. results pharmacology showed that screening activation containing PI3K/Akt/NFkB exerts antineuroinflammatory effects. Results behavioral experiments Pal enhanced in model mice, improved anxiety behavior, significantly damage caused neuroinflammation. could alleviate nucleus tissue. Palmatine IL‐1β. SOD, MDA, CAT, ACH, ACHE hippocampus improved. administration ameliorated LPS‐induced pathway.

Language: Английский

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A meta-analysis of the changes in the Gut microbiota in patients with intractable epilepsy compared to healthy controls

Journal of Clinical Neuroscience, Journal Year: 2024, Volume and Issue: 120, P. 213 - 220

Published: Jan. 29, 2024

Language: Английский

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Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: March 6, 2024

Abstract Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, thorough understanding intricate neural circuits vital development targeted therapies enhancement clinical outcomes. This review begins with an exploration historical evolution techniques used in studying related to epilepsy. It then provides extensive overview diverse employed this domain, discussing their fundamental principles, strengths, limitations, as well application. Additionally, synthesis multiple unveil complexity summarized. Finally, also presents associated epileptic circuits. By providing critical assessment methodologies study circuits, seeks enhance these techniques, stimulate innovative approaches unraveling epilepsy's complexities, ultimately facilitate improved treatment translation Graphical

Language: Английский

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Pharmacological elevation of glutathione inhibits status epilepticus-induced neuroinflammation and oxidative injury

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103168 - 103168

Published: April 24, 2024

Glutathione (GSH) is a major endogenous antioxidant, and its depletion has been observed in several brain diseases including epilepsy. Previous studies our laboratory have shown that dimercaprol (DMP) can elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting biosynthetic enzyme inhibit neuroinflammation vitro. Here we determined 1) role cysteamine as new mechanism by which DMP increases biosynthesis 2) ability to neuronal injury rat kainate model depleted time- concentration- dependent manner cell free system. To guide vivo administration DMP, pharmacokinetic profile was plasma, liver, brain. The results confirmed DMP's cross blood-brain-barrier. Treatment rats with (30mg/kg) liver hippocampus associated increased GCL activity these tissues. levels were significantly (20%) 1h after 30 mg/kg administration. Following once daily, marked attenuation seen SE model. SE-induced inflammatory markers cytokine release, microglial activation, death attenuated treatment. Taken together, highlight importance restoring redox status rescue post epileptogenic insults.

Language: Английский

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The aging brain and late onset drug-refractory epilepsies

Seizure, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

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