Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury

Danhong injection （DHI）, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery ocdusion, and evaluated the potential mechanisms under-lying its effects. Pretreatment with DHI （0.9 and 1.8 mL/kg） resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upreg-ulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI （1.8 mL/kg） administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.

Psoraleae induces hepatotoxicity by affecting bile acid balance

Buguzhi(Psoraleae fructus),the seed of Psoralea corylifolia Linn,is used to treat osteoporosis,nephritis,vitiligo and other diseases.However,long-term routine or overdose of Psoraleae fructus may lead to hepatotoxicity and become a major obstacle of its clinical usage.Psoralen was a key active component of Psoraleae fructus,and a main cause of Psoraleae fructus toxicity.This research was to investigate the hepatotoxicity of psoralen and whether it’s related with bile acid imbalance.Methods:C57BL/6 mice were randomly divided into 4 groups(n=10).Psoralen(20 mg/kg,40 mg/kg and 80 mg/kg)was administrated intragastrically once every day and control group with equivalent water until 4 weeks.Results:The results showed that psoralen caused an increase in liver coefficient and the injury of hepatocytes microstructure of mice.It also inhibited cell viability of HepG2 cells.Mice treated with psoralen exerted liver total bile acid increased while serum total bile acid decreased,which indicated that psoralen-induced liver injury may partly associate with cholestasis.For further study of liver transporters,high dose of psoralen inhibited the expression of some important hepatic efflux transporters(including BSEP,p-gp and ABCG5)in vivo and in vitro.Conclusion:We provide evidence for the first time that psoralen may induce cholestatic hepatotoxicity for the bile acid retention by inhibition on bile acid export pumps.

Simultaneous Determination of Pinoresinol Di-gluco-pyranoside and Pinoresinol Glucoside in Rat Plasma by HPLC-tandem MS/MS for Pharmacokinetic Study

Objective Pinoresinol di-glucopyranoside（PDG） is one of the main active lignans of Eucommiae Cortex considered to be a high-quality antihypertensive drug. In this study the pharmacokinetic process of PDG and its primary in vivo metabolite pinoresinol glucoside（PG） in the portal and jugular vein were surveyed and evaluated simultaneously. Methods A sensitive high-performance liquid chromatography coupled with tandem quadruple mass spectrometry（HPLC-MS/MS） method and sample preparation protocol were developed and validated in method of selectivity, sensitivity, precision, stability, and extraction recovery for the simultaneous determination of PDG and its primary metabolite PG in rat plasma. The double intubation technique was used to simultaneously collect blood from common jugular vein and hepatic portal vein after single ig administration of PDG. Results Using this method, the quantification linearity ranges of PDG and PG in rat plasma were both 0.05-100 ng/mL. This method was successfully applied to the evaluation of the absolute oral bioavailability of PDG and determination of the pharmacokinetic properties of PDG and PG after ig administration of single dose in rats. The bioavailability of PDG at common jugular vein was 51.3% compared to that of 91.6% at hepatic portal vein. Conclusion We conclude that liver is the major conversion site of PDG to PG.