Safranal alleviates pentetrazole-induced epileptic seizures in mice by inhibiting the NF-κB signaling pathway and mitochondrial-dependent apoptosis through GSK-3β inactivation.

Autor: Yan J; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, 310014, China., Li T; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China., Ji K; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China., Zhou X; Department of Pharmacology, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310014, China., Yao W; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Department of Pharmacology, School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, China., Zhou L; Department of Pharmacology, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310014, China., Huang P; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, 310014, China. Electronic address: huangping@hmc.edu.cn., Zhong K; Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Department of Pharmacology, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310014, China. Electronic address: zker12er@zju.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Oct 28; Vol. 333, pp. 118408. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.jep.2024.118408
Abstrakt: Ethnopharmacological Relevance: Saffron, a traditional Chinese medicine, is derived from Crocus sativus L. stigmas and has been reported to possess neuroprotective properties and potentially contribute to the inhibition of apoptosis and inflammation. Safranal, a potent monothyral aldehyde, is a main component of saffron that has been reported to have antiepileptic activity. However, the specific mechanism by which safranal suppresses epileptic seizures via its antiapoptotic and anti-inflammatory properties is unclear.
Aim: To evaluate the effect of safranal on seizure severity, inflammation, and postictal neuronal apoptosis in a mouse model of pentetrazole (PTZ)-induced seizures and explore the underlying mechanism involved.
Materials and Methods: The seizure stage and latency of stage 2 and 4 were quantified to assess the efficacy of safranal in mitigating PTZ-induced epileptic seizures in mice. Electroencephalography (EEG) was employed to monitor epileptiform afterdischarges in each experimental group. The cognitive abilities and motor functions of the mice were evaluated using the novel object recognition test and the open field test, respectively. Neurons were quantified using hematoxylin and eosin staining. Additionally, bioinformatics tools were utilized to predict the interactions between safranal and specific target proteins. Glycogen synthase kinase-3β (GSK-3β), mitochondrial apoptosis-related proteins, and inflammatory factor levels were analyzed through western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations in brain tissue were assessed by ELISA.
Results: Safranal decreased the average seizure stage and increased the lantency of stage 2 and 4 seizures in PTZ-induced epileptic mice. Additionally, safranal exhibited neuroprotective effects on hippocampal CA1 and CA3 neurons and reduced hyperactivity caused by postictal hyperexcitability. Bioinformatics analysis revealed that safranal can bind to five specific proteins, including GSK-3β. By promoting Ser9 phosphorylation and inhibiting GSK-3β activity, safranal effectively suppressed the NF-κB signaling pathway. Moreover, the findings indicate that safranal treatment can decrease TNF-α and IL-1β levels in the cerebral tissues of epileptic mice and downregulate mitochondrial apoptosis-related proteins, including Bcl-2, Bax, Bak, Caspase 9, and Caspase 3.
Conclusion: Safranal can suppress the NF-κB signaling pathway and mitochondrial-dependent apoptosis through GSK-3β inactivation, suggesting that it is a promising therapeutic agent for epilepsy treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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