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Kheir M.M.,Laboratory of Pharmaceutical Science | Kheir M.M.,University of Michigan | Wang Y.,Laboratory of Pharmaceutical Science | Hua L.,Laboratory of Pharmaceutical Science | And 4 more authors.
Food and Chemical Toxicology | Year: 2010

The aim of this study was to investigate the LD50 (median lethal dosage) of berberine (BBR) through three different routes of injection in mice: intravenous (IV) injection, intraperitoneal (IP) injection, and intragastric (IG) oral administration. The concentration of BBR in blood from their IG doses (10.4, 20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different injections were analyzed by high-performance liquid chromatography (HPLC). The LD50 of BBR from IV and IP injections is 9.0386 and 57.6103 mg/kg, respectively; but no LD50 was found in the IG group. A significant difference in bioavailability was observed between the different routes. Furthermore, the concentration of BBR in the blood from different IG doses was also significantly different. However, we discovered an interesting phenomenon indicating that the absorption of BBR by oral administration has a limit, therefore, explaining the difficulty in obtaining an LD50 of BBR for IG injection. From the analysis of BBR content in blood after various administrations, we hypothesized that not only does the concentration of BBR in blood contribute to its acute toxicity, but also the routes of administration may be an important facet that affects this toxicity evaluation. © 2010 Elsevier Ltd. All rights reserved.

Li H.,Laboratory of Pharmaceutical Science | Chen Y.,Laboratory of Pharmaceutical Science | Lei F.,Laboratory of Pharmaceutical Science | Hu J.,Laboratory of Pharmaceutical Science | And 4 more authors.
Zhongguo Zhongyao Zazhi | Year: 2010

Objective: To investigate brazilein's role in energy metabolism of cerebral ischemia-reperfusion in mice. Method: Fourty mice were randomly divided into the sham group, ischemia group, brazilein 5 mg·kg-1 group and brazilein 10 mg·kg-1 group, each with ten cases. Cerebral ischemia model was the built. Mice were injected with brazilein three days before the operation, then they were killed. Cerebrum homogenate was prepared for the detecting of ATP, ADP, AMP and lactic acid by HPLC, expressions of MCT1 and MCT2 in mRNA level by RT-PCR. Result: The lactic acid in cerebrum increased sharply 20 minutes after cerebral ischemia and decreased 1 hour after reperfusion, then returned to the normal level 24 hours after reperfusion. The charge of energy decreased significantly at the beginning of the ischemia-reperfusion, and the charge restored 1 hour after reperfusion though it was still much lower than the normal level at the time point of 24 hours. Moreover, MCT1 and MCT2 upregulated accompanied with the increase of lactate, MCT2 mRNA enhanced in brazilein 5 mg·kg-1 group (P < 0.05) while both the two factors increased in brazilein 10 mg· kg-1 group (P < 0.01). Conclusion: Brazilein might protect neurons by changing the charge of energy.

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