Neuroprotective effects of xiao-xu-ming decoction against ischemic neuronal injury in vivo and in vitro.
BACKGROUND
Xiao-Xu-Ming decoction (XXMD) has long been employed clinically to treat stroke in traditional Chinese Medicine.


OBJECTIVE
To investigate the neuroprotective effects of XXMD in vivo and in vitro stroke models and determine involved mechanisms.


METHODS
Two models (four-vessel occlusion in adult Wistar rats and oxygen-glucose deprivation primary cultured neurons) were employed to mimic ischemia-reperfusion damage, in vivo and in vitro, respectively. The effects of XXMD were investigated with respect to neuronal damage, activity of caspase-3 and expression of Bcl-2 in CA1 region of hippocampus after ischemia. The cognitive ability was measured 7 days after ischemia/reperfusion by using Morris water maze.


RESULTS
Oral administration of XXMD significantly increased the density of neurons that survived in the CA1 region of hippocampus on the 3rd and 7th day after transient global ischemia was induced in a dose-dependent manner. XXMD ameliorated severe deficiencies in spatial cognitive performance induced by transient global ischemia. Inhibition of caspase-3 activity and up-regulation of Bcl-2 expression were induced in the high dose of XXMD-treated rats after ischemia. In oxygen-glucose deprivation model, both XXMD extract and drug-containing serum prepared from blood of high dose of XXMD-treated rats inhibited apoptotic neuronal death at 24h after reoxygenation.


CONCLUSIONS
Our results clearly demonstrated that XXMD is neuroprotective and appears to influence deleterious pathological processes that are activated after the onset of ischemia.
Zhu
Xin-Hong
XH
Department of Neurobiology, Southern Medical University, 1023S Shatai Road, Guangzhou 510515, China.
Li
Shu-Ji
SJ
Hu
Hong-Hai
HH
Sun
Li-Rong
LR
Das
Manas
M
Gao
Tian-Ming
TM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C548754:xiao-xu-ming; D053148:Caspase 3