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.
Yoon
Sung-Ryul
SR
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Jo
Young-Jun
YJ
Yang
Shulong
S
Kim
Yun-Bae
YB
Nam
Sang-Yoon
SY
Kim
Hyoung-Chun
HC
Hong
Jin Tae
JT
Oh
Ki-Wan
KW
D000284:Administration, Oral; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000517:prevention & control*; D031957:Ziziphus / Q000737:chemistry*
D000470:Alkaloids; D000927:Anticonvulsants; D002712:Chlorides; D010456:Peptides, Cyclic; C523394:Sanjoinine A; D007608:Kainic Acid; D002118:Calcium