No abstract

− This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through γ-aminobutyric acid (GABA) receptor Cl -channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and Cl -sensitive fluorescence probe were used to detect the expression of GABA A receptor subunits and Cl -influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 µM) increased Cl -influx in primary cultured cerebellar granule cells, and selectively increased the GABA A receptor α-subunit expression, but had no effect on the abundance of β or γ-subunits. Chronic treatment with 20 µM honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through GABA A receptor Cl -channel activation.

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.