title: Pentamethylquercetin (PMQ) reduces thrombus formation by inhibiting platelet function.
abstract: Flavonoids exert both anti-oxidant and anti-platelet activities in vitro and in vivo. Pentamethylquercetin (PMQ), a polymethoxylated flavone derivative, has been screened for anti-carcinogenic and cardioprotective effects. However, it is unclear whether PMQ has anti-thrombotic effects. In the present study, PMQ (20 mg/kg) significantly inhibited thrombus formation in the collagen- epinephrine- induced acute pulmonary thrombosis mouse model and the ferric chloride-induced carotid injury model. To explore the mechanism, we evaluated the effects of PMQ on platelet function. We found that PMQ inhibited platelet aggregation and granule secretion induced by low dose agonists, including ADP, collagen, thrombin and U46619. Biochemical analysis revealed that PMQ inhibited collagen-, thrombin- and U46619-induced activation of Syk, PLCγ2, Akt, GSK3β and Erk1/2. Therefore, we provide the first report to show that PMQ possesses anti-thrombotic activity in vivo and inhibited platelet function in vitro, suggesting that PMQ may represent a potential therapeutic candidate for the prevention or treatment of thrombotic disorders.
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Ming-Lu
authors.initials: ML
authors.lastname: Liang
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Xing-Wen
authors.initials: XW
authors.lastname: Da
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Ao-Di
authors.initials: AD
authors.lastname: He
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Guang-Qiang
authors.initials: GQ
authors.lastname: Yao
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Ji-Zhou
authors.initials: JZ
authors.lastname: Xiang
authors.affiliation: 1] Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China [2] The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Zhang-Yin
authors.initials: ZY
authors.lastname: Ming
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: C548139:3,3',4',5,7-pentamethylquercetin; D010975:Platelet Aggregation Inhibitors; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011794:Quercetin; D013917:Thrombin