In-vivo and in-vitro studies on the effect of Huang-Lian-Jie-Du-Tang on nimodipine transport across rat blood-brain barrier.
Huang-Lian-Jie-Du-Tang (HLJDT), an aqueous extract of Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae (3:2:2:3) is an important multi-herb remedy in traditional Chinese medicine (TCM). The aim of this study was to evaluate the effect of HLJDT on nimodipine transport across rat blood-brain barrier (BBB). It was found that in-vivo the brain concentrations of nimodipine significantly increased when rats were pretreated with HLJDT. In-vitro, the serum of HLJDT-treated rats increased the accumulation of nimodipine in primary cultured rat brain microvessel endothelial cells (rBMECs) and decreased the expression of P-glycoprotein (P-gp) on rBMECs. Our previous study showed that the peak concentration of baicalin and berberine in rats after administration of HLJDT was 5 mug mL(-1) and 10 ng mL(-1), respectively. This study showed that 5 mug mL(-1) baicalin significantly increased the accumulation of nimodipine in rBMECs, while 10 ng mL(-1) berberine had no effect on the accumulation of nimodipine in rBMECs. Both the in-vivo and in-vitro experimental findings indicated that HLJDT pretreatment may alter the transport of nimodipine across rat BBB.
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.
Dong Mei
DM
Zhang
Zhen Wei
ZW
He
Xiao Dong
XD
Liu
Yang
Y
Li
Lin
L
Xie
Guang Ji
GJ
Wang
Li
L
Liu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000493:pharmacokinetics; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009553:Nimodipine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020112:Rhodamine 123 / Q000378:metabolism / Q000493:pharmacokinetics; D044967:Serum
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C045607:huang-lien-chieh-tu-tang; D020112:Rhodamine 123; D009553:Nimodipine