title: Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis.
abstract: The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography-photodiode array detector/(-)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 μM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis.
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Tang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jiawang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Wenyun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Ma
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China ; Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000737:chemistry; D053630:Depsides / Q000737:chemistry; D005434:Flow Cytometry; D062385:Hydroxybenzoates / Q000737:chemistry; D037602:Isodon / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D019007:P-Selectin / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy*; D000097123:Rosmarinic Acid
chemical_list: D000244:Adenosine Diphosphate; D016718:Arachidonic Acid; D002934:Cinnamates; D053630:Depsides; D062385:Hydroxybenzoates; D019007:P-Selectin; D010936:Plant Extracts; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin; D000097123:Rosmarinic Acid; C017616:phenolic acid
keywords: R. rubescens; antithrombotic ingredient; sP-selectin