Neuroprotective effects of Xiao-Xu-Ming decoction against ischemic neuronal injury in vivo and in vitro

Xiao-Xu-Ming decoction (XXMD) has long been employed clinically to treat stroke in traditional Chinese Medicine. To investigate the neuroprotective effects of XXMD in vivo and in vitro stroke models and determine involved mechanisms. 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. 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 24 h after reoxygenation. Our results clearly demonstrated that XXMD is neuroprotective and appears to influence deleterious pathological processes that are activated after the onset of ischemia.