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α-Linolenic acid ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures via down-regulating JAK2/STAT3 pathway

Published online by Cambridge University Press:  22 May 2024

Xin Zeng Open the ORCID record for Xin Zeng [Opens in a new window] ,
Fei Luo ,
Ya-hong Cheng ,
Jiefang Gao  and
Ding Hong
Xin Zeng
Affiliation:
Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, The Second Clinical Medical College of North Sichuan Medical College, Nanchong Central Hospital, Nanchong, People’s Republic of China
Fei Luo
Affiliation:
Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China
Ya-hong Cheng
Affiliation:
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430000 Hubei, People’s Republic of China
Jiefang Gao
Affiliation:
Central Laboratory, the First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, People’s Republic of China
Ding Hong*
Affiliation:
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430000 Hubei, People’s Republic of China
*
*Corresponding author: Ding Hong, email 1298601247@qq.com
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Abstract

Epilepsy ranks fourth among neurological diseases, featuring spontaneous seizures and behavioural and cognitive impairments. Although anti-epileptic drugs are currently available clinically, 30 % of epilepsy patients are still ineffective in treatment and 52 % of patients experience serious adverse reactions. In this work, the neuroprotective effect of α-linolenic acid (ALA, a nutrient) in mice and its potential molecular mechanisms exposed to pentylenetetrazol (PTZ) was assessed. The mice were injected with pentetrazol 37 mg/kg, and ALA was intra-gastrically administered for 40 d. The treatment with ALA significantly reduced the overall frequency of epileptic seizures and improved the behaviour impairment and cognitive disorder caused by pentetrazol toxicity. In addition, ALA can not only reduce the apoptosis rate of brain neurons in epileptic mice but also significantly reduce the content of brain inflammatory factors (IL-6, IL-1 and TNF-α). Furthermore, we predicted that the possible targets of ALA in the treatment of epilepsy were JAK2 and STAT3 through molecular docking. Finally, through molecular docking and western blot studies, we revealed that the potential mechanism of ALA ameliorates PTZ-induced neuron apoptosis and neurological impairment in mice with seizures by down-regulating the JAK2/STAT3 pathway. This study aimed to investigate the anti-epileptic and neuroprotective effects of ALA, as well as explore its potential mechanisms, through the construction of a chronic ignition mouse model via intraperitoneal PTZ injection. The findings of this research provide crucial scientific support for subsequent clinical application studies in this field.

Keywords

α-Linolenic acidEpilepsyJAK2/STAT3 signalling pathwayNeuron apoptosisNeuroinflammationPentylenetetrazol toxicity
Type
Research Article
Information
British Journal of Nutrition , First View , pp. 1 - 12
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

†

These authors contributed equally to this work.

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