title: Inhibitory effect of salvianolate on human cytochrome P450 3A4 in vitro involving a noncompetitive manner.
abstract: Salvianolic acid B (Sal B), which is purified from Danshen, is a popular herb extract. Sal B has anti-oxidative, anti-inflammatory, anti-hypoxic, anti-arteriosclerotic and anti-apoptotic properties. This substance can also ameliorate brain injury or neurodegenerative diseases. The listed drug Salvianolate, which contains a substantial amount of Sal B, has been used for the treatment of coronary heart disease. Our present work aimed to evaluate the inhibitory effect of salvianolate on seven cytochrome P450 isoforms (CYP450), namely, CYP1A2, CYP2A6, CYP2E1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, in human liver microsomes (HLMs) and recombinant enzymes through high-performance liquid chromatography (HPLC) assay. Salvianolate have a potent inhibitory effect on CYP3A4 activity with IC50 values of 1.438 (HLMs) and 3.582 (recombinant cDNA-expressed CYP3A4) mg/L, respectively. Salvianolate strongly dose, but not time-dependently decreased CYP3A4 activity in HLMs. The typical Lineweaver-Burk plots showed that Salvianolate inhibited CYP3A4 activity noncompetitively, with a Ki value of 2.27 mg/L in HLMs. Other CYP450 isoforms are not markedly affected by Salvianolate. These findings indicate that salvianolate may be involved in potential drug interactions when co-administrated with CYP3A4 substrates.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha 410008, P. R. China ; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics Changsha 410078, P. R. China.
authors.forename: Chong-Zhen
authors.initials: CZ
authors.lastname: Qin
authors.affiliation: Shanghai Green Valley Pharmaceutical Co., Ltd. Shanghai 201203, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha 410008, P. R. China ; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics Changsha 410078, P. R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha 410008, P. R. China ; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics Changsha 410078, P. R. China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Mao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha 410008, P. R. China ; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics Changsha 410078, P. R. China.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
keywords: CYP3A4; Salvianolate; drug-drug interaction; human liver microsomes; noncompetitive inhibition