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.
Zhang
Dong Mei
DM
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.
He
Zhen Wei
ZW
Liu
Xiao Dong
XD
Li
Yang
Y
Xie
Lin
L
Wang
Guang Ji
GJ
Liu
Li
L
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