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Bupleurum chinense DC. is a traditional Chinese medicine with a long medicinal history and is often used as the main ingredient in prescription drugs for epilepsy. The aerial parts of B. chinense DC. have similar efficacy and composition to B. chinense DC. Therefore, we speculated that the aerial parts of B. chinense DC. could be used in the treatment of epilepsy. Polysaccharides from the aerial parts of B. chinense DC. were selected to explore their therapeutic effects on epilepsy and their potential mechanism of action. The study is aimed at clarifying the antiepileptic effects of the polysaccharides from the aerial parts of B. chinense DC. and their potential underlying mechanisms. The chemical profile of the aerial parts of B. chinense DC. polysaccharides (ABP) was characterized by FT-IR spectrum and HPLC chromatogram. To determine the therapeutic effects of ABPs on epilepsy, we established a kainic acid- (KA-) induced rat model of epilepsy, and through H&E staining, Nissl staining, immunohistochemistry, biochemical analysis, ELISA, and Western blot analysis, we explored the mechanisms underlying the therapeutic effects of ABPs on epilepsy. The monosaccharide content of ABP included galacturonic acid (45.19%), galactose (36.63%), arabinose rhamnose (12.13%), and mannose (6.05%). Moreover, the average molecular weight of ABP was 1.38 × 10 3  kDa. ABP could improve hippocampal injuries and neuronal function in the KA-induced epilepsy rat model. ABP significantly inhibited oxidative stress in the hippocampus of KA-induced rats. More importantly, ABP could regulate TREM2 activation in the PI3K/Akt/GSK-3 β pathway to inhibit neuronal apoptosis, including increasing the expression of superoxide dismutase and lactate dehydrogenase and decreasing the expression of malondialdehyde. The current study defined the potential role of ABP in inhibiting the development of epilepsy, indicating that ABP could upregulate TREM2 to alleviate neuronal apoptosis, by activating the PI3K/Akt/GSK-3 β pathway and oxidative stress in epilepsy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Xiaomao Li et al.)