Sanjoinine A isolated from Semen Zizyphi Spinosi protects against kainic acid-induced convulsions

These experiments were performed to know whether sanjoinine A, a component of the alkaloid fraction of Semen Zizyphi Spinosi, acts as an anti-convulsive agent in the kainic acid (KA)-induced experimental convulsion model and whether these effects are mediated by decreased intracellular calcium. Oral administration of sanjoinine A (4 and 8 mg/kg) increased the survival rate and latency of convulsion onset, and decreased the seizure scores and the weight loss induced by intraperitoneal (i.p.) injection of KA (50 mg/kg) in mice. In addition, sanjoinine A protected against neuronal damage and apoptosis in the hippocampus after KA administration, as analyzed by using immunohistochemistry and TUNEL assay. Sanjoinine A also significantly blocked seizure-form electroencephalogram alterations induced by KA. Moreover, in cultured rat neuronal cells, sanjoinine A inhibited KA-induced cell death, as measured by propidium iodide detection. Sanjoinine A also increased intracellular chloride and inhibited the elevation of intracellular calcium induced by KA. Sanjoinine A, therefore protects against KA-induced convulsions by increasing intracellular chloride and reducing intracellular calcium levels.