Schaftoside Suppresses Pentylenetetrazol-Induced Seizures in Zebrafish via Suppressing Apoptosis, Modulating Inflammation, and Oxidative Stress

Abstract

The lack of disease-modifying therapeutic strategies against epileptic seizures has caused a surge in preclinical research focused on exploring and developing novel therapeutic candidates for epilepsy. Compounds from traditional Chinese medicines (TCMs) have gained much attention for a plethora of neurological diseases, including epilepsy. Herein, for the first time, we evaluated the anticonvulsive effects of schaftoside (SS), a TCM, on pentylenetetrazol (PTZ)-induced epileptic seizures in zebrafish and examined the underlying mechanisms. We observed that SS pretreatments significantly suppressed seizure-like behavior and prolonged the onset of seizures. Zebrafish larvae pretreated with SS demonstrated downregulation of <i>c-fos</i> expression during seizures. PTZ-induced upregulation of apoptotic cells was decreased upon pretreatment with SS. Inflammatory phenomena during seizure progression including the upregulation of interleukin 6 (<i>IL-6</i>), interleukin 1 beta (<i>IL-1β</i>), and nuclear factor kappa-light-chain-enhancer of activated B cells (<i>NF-κB</i>) were downregulated upon pretreatment with SS. The PTZ-induced recruitment of immunocytes was in turn reduced upon SS pretreatment. Moreover, SS pretreatment modulated oxidative stress, as demonstrated by decreased levels of catalase (<i>CAT</i>) and increased levels of glutathione peroxidase-1a (<i>GPx1a</i>) and manganese superoxide dismutase (<i>Mn-SOD</i>). However, pretreatment with SS modulated the PTZ-induced downregulation of the relative enzyme activity of CAT, GPx, and SOD. Hence, our findings suggest that SS pretreatment ameliorates PTZ-induced seizures, suppresses apoptosis, and downregulates the inflammatory response and oxidative stress, which potentially protect against further seizures in zebrafish.