title: Screening of direct thrombin inhibitors from Radix Salviae Miltiorrhizae by a peak fractionation approach.
abstract: Thrombin plays a significant role in thromboembolic disease. In this work, a peak fractionation approach combined with an activity assay method was used to screen direct thrombin inhibitors from Radix Salviae Miltiorrhizae (RSM), a famous herbal remedy for the treatment of cardiovascular diseases in China. A total of 91 fractions were collected from the RSM extract, and 19 fractions out of them showed thrombin inhibitory effects with dose-effect relationship. Among them, three compounds were unambiguously identified as 15, 16-dihydrotanshinone I, cryptotanshinone and tanshinone IIA with IC50 values of 29.39, 81.11 and 66.60μM, respectively. The three compounds were reported with direct thrombin inhibition activities for the first time and their ligand-thrombin interactions were explored by a molecular docking research. These results may contribute to explain the medical benefit of RSM for the prevention and treatment of cardiovascular diseases.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China. Electronic address: chenj2002@gmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D045784:Abietanes / Q000032:analysis; D000475:Alkenes / Q000032:analysis; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D018517:Plant Roots / Q000737:chemistry; D059808:Polyphenols / Q000032:analysis; D011955:Receptors, Drug / Q000737:chemistry; D015203:Reproducibility of Results; D027561:Salvia miltiorrhiza / Q000737:chemistry*
chemical_list: D045784:Abietanes; D000475:Alkenes; D000991:Antithrombins; D059808:Polyphenols; D011955:Receptors, Drug; C568740:salvianolic acid; C021751:tanshinone
keywords: High-throughput screening; Peak fractionation; QTOF mass spectrometry; Radix Salviae Miltiorrhizae; Thrombin inhibitor