Arisaema Cum Bile possesses significantly antiepileptic effects through regulation of PI3K/Akt/Nrf2 signaling pathways

Abstract

This paper intended to study the mechanism and active ingredients of ACB anti-epilepsy. The antiepileptic activity of ACB validated in PTZ kindled rats, ACB could increase the seizure latency and reduce seizure duration, attenuate spatial learning and memory deficits, improve hippocampus neuronal damage and regulate unbalanced neurotransmitters. Furthermore, network pharmacology and molecular docking analysis predicted four potential active compounds, in addition, PI3K/Akt signal pathway may be the main signal pathway of ACB anti-epilepsy. In vitro, ACB greatly increased the vitality and reduced apoptosis of PC12 cells exposed to H2O2. Additionally, ACB elevated Bcl-2 and downregulated C-caspase-3 and Bax proteins expression. Importantly, ACB improved the phosphorylation of PI3K and Akt in H2O2-stimulated PC12 cells, and stimulated the nuclear transfer of Nrf2. These findings indicated that ACB has effective on antiepileptic by activating of the PI3K/Akt/Nrf2 pathway to reduce oxidative stress and neuronal cell apoptosis.