Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis.
Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis.
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冬凌草叶水提取物：形成纳米颗粒，靶向 P-选择素，抑制血栓形成
DOI：
10.2147/ijn.s91316
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发表时间：
2015
影响因子：
8
通讯作者：
Peng S
中科院分区：
文献类型：
--
作者：
Wang Y;Tang J;Zhu H;Jiang X;Liu J;Xu W;Ma H;Feng Q;Wu J;Zhao M;Peng S
冬凌草热水提取物传统上被用作抗血栓药物。为了探讨其抗血栓作用及其机制，本研究进行了一系列的体内外实验。体外血小板聚集实验表明，冬凌草叶水提物(AERL)对凝血酶、花生四烯酸、二磷酸腺苷和血小板活化因子诱导的血小板聚集的半数抑制浓度范围为0.12~1.43 mg/mL。AERL抑制大鼠血栓形成的最小有效口服剂量为25 mg/kg。体外和体内作用均与AERL浓度依赖地抑制sP-选择素释放有关。在水中，AERL形成纳米颗粒，其大小取决于浓度。将高效液相色谱-光电二极管阵列检测器/(−)电喷雾电离串联质谱仪鉴定的5个核苷酸、21个酚酸和4个二萜类化合物对接到P-选择素的活性部位，预测迷迭香酸是其抗血栓活性成分。在流式细胞仪分析中，1μM迷迭香酸有效地抑制花生四烯酸激活的血小板释放sP-选择素。在大鼠模型中，口服迷迭香酸5 mg/kg可有效抑制血栓形成。
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.