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

• Published in: British journal of nutrition 2024-07, Vol.132 (1), p.1-12
• Main Authors: Zeng, Xin, Luo, Fei, Cheng, Ya-hong, Gao, Jiefang, Hong, Ding
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Biotechnology; Brain; Brain damage; Brain research; Cell cycle; Cognitive ability; Convulsions & seizures; Epilepsy; Health services; Impairment; Inflammation; Janus kinase 2; Kinases; Laboratory animals; Linolenic acid; Medical research; Memory; Metabolism and Metabolic Studies; Molecular docking; Molecular modelling; Neurological complications; Neurological diseases; Neuroprotection; Patients; Proteins; Seizures; Software; Stat3 protein; Toxicity; Tumor necrosis factor-α
• ISSN: 0007-1145; 1475-2662; 1475-2662
• DOI: 10.1017/S0007114524000989

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.