ABSTRACT
OBJECTIVE@#The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study.@*METHODS@#Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.@*RESULTS@#Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed.@*CONCLUSION@#In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.
ABSTRACT
Objective To investigate the effect and significance of microglia/macrophage activation prior to cerebral ischemic preconditioning (CIP) in regulating toll-like receptors 2 (TLR2)/nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in early stage after ischemic brain injury in rats.Methods Thirty healthy male SD rats were selected and divided into normal control group,sham operation group,ischemia group,intervention group and treatment group according to random number table,with six rats per group.A rat model of focal permanent cerebral infarct was established by occlusion of middle cerebral artery (MCAO).CIP was performed by local ischemia-reperfusion.Minocycline was used to inhibit microglia/macrophage activation after CIP.Features of microglia/macrophage activation after CIP were detected by immunofluorescence; mRNA expressions of predominant factors (NF-κB inhibitor α,IκB-α;tumor necrosis factor α,TNF-α) of TLR2/NF-κB inflammatory signaling pathway in parietal cerebral cortex by in situ hybridization method; death rate by Kaplan-meier survival curves; neurological deficits by a 5-point neurological scale; brain infarct size by triphenyl tetrazolium chloride (TTC) staining.Results Microglia/macrophage started activation at one hour after cerebral ischemic injury in preconditioning group and presented a significant increase at 12 hours.Speed and range of activation were higher in preconditioning group than in ischemic group.IκB-α mRNA in preconditioning group started expression at one hour.TNF-α mRNA in preconditioning group remained a low expression in 12 hours and had a significantly lower peak value as compared with that in ischemic group (P ＜ 0.05).CIP increased rat survival rate significantly,improved nerve function and reduced infarction size when compared with the ischemia group (P ＜ 0.05).Minocycline inhibited nerve protection by CIP significantly (P ＜0.05).Conclusion CIP induces rapid activation of microglia/macrophage in early period of rat cerebral ischemic injury and provides brain protection probably via inhibition of TLR2/NF-κB activity and inflammatory overreaction to cerebral ischemia.