Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway.
OBJECTIVE
Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure.


METHODS
PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1β and TNF-α were then determined.


RESULTS
In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1β and TNF-α expression. In hippocampal neurons exposed to PTZ, p-mTOR and p-70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa.


CONCLUSIONS
SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway.
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
Ming
M
Ye
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
Yong-Feng
YF
Bi
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
Li
L
Ding
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
Wei-Wei
WW
Zhu
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China. Electronic address: gaowei@suda.edu.cn.
Wei
W
Gao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole; D010766:Phosphorylation / Q000187:drug effects; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D009828:Oleanolic Acid; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; C025759:saikosaponin D; D020123:Sirolimus; D010433:Pentylenetetrazole
Anticonvulsant; Epilepsy; Hippocampus; Radix bupleuri; mTOR