title: P‑glycoprotein inhibition increases the transport of dauricine across the blood‑brain barrier.
abstract: Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. The aim of the present study was to investigate the role of P‑glycoprotein in the transport of dauricine across the blood‑brain barrier by pre‑treatment with the P‑glycoprotein inhibitor verapamil. Sprague Dawley rats were divided into a verapamil group (pretreated with verapamil at a dose of 20 mg/kg) and a control group (pretreated with the same volume of normal saline). After 90 min, the animals were injected intravenously with dauricine (10 mg/kg). At 15, 30 and 60 min after dauricine administration, the levels of dauricine in the blood and brain were detected by high‑performance liquid chromatography. Compared with the control group, the dauricine concentration in the brains of the rats in the verapamil group was significantly increased. Furthermore, the brain‑plasma ratio of dauricine in the rats pretreated with verapamil was significantly higher than that of the animals in the control group. However, there was no difference identified between dauricine levels in the plasma of the verapamil and the control groups. The results indicated that dauricine is able to pass the blood‑brain barrier, and that P‑glycoprotein has an important role in the transportation of dauricine across the blood‑brain barrier.
authors.affiliation: Key Laboratory of Chinese Materia Medica of Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Dong
authors.affiliation: Key Laboratory of Chinese Materia Medica of Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.affiliation: Key Laboratory of Chinese Materia Medica of Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chinese Materia Medica of Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Bingyou
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory of Chinese Materia Medica of Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China.
authors.forename: Gao-Wa
authors.initials: GW
authors.lastname: Eerdun
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D044182:Benzylisoquinolines / Q000032:analysis / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008297:Male; D031603:Menispermum / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines / Q000032:analysis / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D044182:Benzylisoquinolines; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; C035934:dauricine; D014700:Verapamil