ABSTRACT
<p><b>OBJECTIVE</b>To explore the effects and molecular mechanisms of the combination between total Astragalus extract (TAE) and total Panax notoginseng saponins (TPNS) against cerebral ischemia-reperfusion injury.</p><p><b>METHODS</b>C57BL/6 mice were randomly divided into sham-operated group, model group, TAE (110 mg/kg) group, TPNS (115 mg/kg) group, TAE-TPNS combination group and Edaravone (4 mg/kg) group, treated for 4 days, then, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery (CCA) ligation for 20 min followed by reperfusion for 1 and 24 h.</p><p><b>RESULTS</b>TPNS could increase adenosine triphosphate (ATP) level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate (ADP) contents and Na-K-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinase1/2 (p-JNK1/2), cytochrome C (Cyt C), cysteine aspartic acid-specific protease (Caspase)-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone.</p><p><b>CONCLUSION</b>The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To investigate effect of the four kinds of active fractions extracted from Buyang Huanwu Decoction (BYHWD) on caspase expression in rats after focal cerebral ischemic reperfusion.</p><p><b>METHODS</b>The focal cerebral ischemia/reperfusion model rats were established by middle cerebral artery occlusion for 2 hrs followed with reperfusion for 46 hrs. Before and at 12th, 24th and 36th hour after cerebral ischemia, the rats were administered with alkaloid, glycoside, polysaccharide and aglycone from BYHWD respectively, and nimodipine was given as control medicine to observe the effect of them on protein expression of caspase-1, caspase-3 and caspase-8 using immunohistochemical method.</p><p><b>RESULTS</b>Protein expression of caspase-1 and caspase-3 increased in the injured lateral brain tissue after cerebral ischemia/reperfusion. Caspase-1 expression were observed mainly in choroids, while caspase-3 expression in hippocampus, cortex and medulla. All the four kinds of active fractions from BYHWD could inhibit caspase-1 expression, while nimodipine couldn't. Caspase-3 expression in hippocampus and medulla could be inhibited by alkaloid, that in hippocampus, cortex and medulla could be inhibited by glycoside and aglycone, and that in hippocampus and medulla by nimodipine, however, polysaccharide showd no effect on it. As for caspase-8 expression, no effect on it was shown in all groups.</p><p><b>CONCLUSION</b>Alkaloid, glycoside, polysaccharide and aglycone from BYHWD could relieve the inflammatory reaction occurred after cerebral ischemia/reperfusion by inhibiting caspase-1 expression to decrease production of inflammatory cytokine. Alkaloid, glycoside and aglycone could reduce neuronal apoptosis by inhibiting caspase-3 expression to antagonize the delayed neuronal death after cerebral ischemia. The 4 kinds of active fractions may be the main material basis for BYHWD in preventing ischemia/reperfusion cerebral injury.</p>