Herbal formula FBD extracts prevented brain injury and inflammation induced by cerebral ischemia-reperfusion

The aim of this work was to verify neuroprotective and anti-inflammatory properties of FBD, a herbal formula composed of Poria cocos, Atractylodes macrocephala and Angelica sinensis, in ICR mice subjected to repetitive 10 min of common carotid arteries occlusion followed 24 h reperfusion. Intragastrical pretreatment with supercritical carbon dioxide extract (FBD-CO(2), 37.5 mg/kg) twice daily for 3.5 d, significantly reduced Evans Blue influx, neuron specific enolase (NSE) efflux, brain infarction (all p<0.05), also inhibited polymorphonuclear leukocytes (PMNs) infiltration (p<0.001), suppressed secretion of tumor necrosis factor (TNF)-alpha in blood (p<0.05), interleukin (IL)-1beta and IL-8 in brain (both p<0.01), and down-regulated cerebral expression of phosphor-IkappaB-alpha and phosphor-nuclear factor kappa-B (NF-kappaB), whether coupled with aqueous extract (FBD-H(2)O, 150 mg/kg) or not. Moreover, FBD-CO(2) (0.1-10 microg/ml) inhibited 0.1 microM phorbol myristate acetate-evoked oxidative burst in rat PMNs, 20 ng/ml TNF-alpha-triggered PMNs adhesion to ECV304 endothelial cells, and PMNs neurotoxicity to PC12 neuron-like cells as well as NSE release (IC(50) 1.30, 0.98, 0.24 and 0.82 microg/ml, respectively). Our study demonstrated that FBD-CO(2) prevented brain ischemia/reperfusion injury, at least in part, by limiting PMNs infiltration and neurotoxicity mediated by TNF-alpha, IL-1beta and IL-8, via inhibition on NF-kappaB activation.