Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis

Yuji Wang,1 Jingcheng Tang,1 Haimei Zhu,1 Xueyun Jiang,1 Jiawang Liu,1 Wenyun Xu,1 Haiping Ma,1 Qiqi Feng,1 Jianhui Wu,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of...

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Autores principales:	Wang Y, Tang J, Zhu H, Jiang X, Liu J, Xu W, Ma H, Feng Q, Wu J, Zhao M, Peng S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8df00ac3a0404f9ca565df3249528546
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spelling	oai:doaj.org-article:8df00ac3a0404f9ca565df32495285462021-12-02T00:20:48ZAqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis1178-2013https://doaj.org/article/8df00ac3a0404f9ca565df32495285462015-11-01T00:00:00Zhttps://www.dovepress.com/aqueous-extract-of-rabdosia-rubescens-leaves-forming-nanoparticles-tar-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yuji Wang,1 Jingcheng Tang,1 Haimei Zhu,1 Xueyun Jiang,1 Jiawang Liu,1 Wenyun Xu,1 Haiping Ma,1 Qiqi Feng,1 Jianhui Wu,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing 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; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan 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. Keywords: R. rubescens, sP-selectin, antithrombotic ingredient Wang YTang JZhu HJiang XLiu JXu WMa HFeng QWu JZhao MPeng SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6905-6918 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang Y Tang J Zhu H Jiang X Liu J Xu W Ma H Feng Q Wu J Zhao M Peng S Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
description	Yuji Wang,1 Jingcheng Tang,1 Haimei Zhu,1 Xueyun Jiang,1 Jiawang Liu,1 Wenyun Xu,1 Haiping Ma,1 Qiqi Feng,1 Jianhui Wu,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing 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; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan 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. Keywords: R. rubescens, sP-selectin, antithrombotic ingredient
format	article
author	Wang Y Tang J Zhu H Jiang X Liu J Xu W Ma H Feng Q Wu J Zhao M Peng S
author_facet	Wang Y Tang J Zhu H Jiang X Liu J Xu W Ma H Feng Q Wu J Zhao M Peng S
author_sort	Wang Y
title	Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
title_short	Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
title_full	Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
title_fullStr	Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
title_full_unstemmed	Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis
title_sort	aqueous extract of rabdosia rubescens leaves: forming nanoparticles, targeting p-selectin, and inhibiting thrombosis
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/8df00ac3a0404f9ca565df3249528546
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Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis

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