Down-regulation of P-glycoprotein expression contributes to an increase in Danshensu accumulation in the cerebral ischemia/reperfusion brain.

Abstract

P-glycoprotein (P-gp) plays a key role in the distribution and elimination of many clinically important therapeutic substances. P-gp inhibition is capable of increasing the concentration of various drugs in the brain. Danshensu is a main hydrophilic constituent of Salvia miltiorrhiza Bunge which is used traditionally to treat cerebrovascular diseases. In the present study, the effects of cerebral ischemia/reperfusion on the transport of Danshensu in the brain were observed by assaying the concentration at 15, 30 and 60 min after cerebral ischemia/reperfusion in the brain of rats. Furthermore, the expression of P-gp in the brain was also measured. Results showed that Danshensu concentrations in the ischemic hemisphere significantly increased compared to those in the non-ischemic hemisphere and the brain of the sham group. P-gp expression was inhibited by cerebral ischemia/reperfusion to some extent, and down-regulated much more by Danshensu treatment. The findings indicate that the down-regulation of P-gp expression induced by both cerebral ischemia/reperfusion and Danshensu treatment contributes to the increase of Danshensu accumulation in the brain.

• Authors: Yating Chong, Tian Wang, Wenyan Wang, Leiming Zhang, Chong Li, Pengfei Yu, Hongsheng Wang, Fenghua Fu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 5 Issue 3 Pg. 812-6 (03 2012) ISSN: 1791-3004 [Electronic] Greece
• PMID: 22134431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Drugs, Chinese Herbal
• Lactates
• 3,4-dihydroxyphenyllactic acid

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Animals
• Brain (metabolism)
• Chromatography, High Pressure Liquid
• Down-Regulation
• Drugs, Chinese Herbal (analysis, metabolism, therapeutic use)
• Lactates (analysis, metabolism, therapeutic use)
• Male
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Salvia miltiorrhiza (chemistry)
• Spectrometry, Mass, Electrospray Ionization