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.

Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors

“…The remaining eight tested components, including salvianolic acid D (33.5 ± 8.6% inhibition), were weakly inhibiting or inactive. Another Danshen component, rosmarinic acid, was previously shown to be more potent in antagonizing thrombin-induced than ADP-induced platelet aggregation 30 . Our results confirmed that it is indeed a weak ligand of the P2Y 12 receptor (31.6 ± 6.2% inhibition at 100 µM).…”

A Dual-Targeting Ruthenium Nanodrug that Inhibits Primary Tumor Growth and Lung Metastasis by the PARP/ATM Pathway

“…We determined the self-assembly properties and protein binding characteristics to evaluate its targeting characteristics. 2b remained stable for 96 h (44), and the size of 2b was 50-100 nm, which was more favorable for targeting tumors than ligand 2 based on the EPR effect (45). In addition, 2b could strongly bind to TF (27).…”

A dual-targeting ruthenium nanodrug that inhibits primary tumor growth and lung metastasis via the PARP/ATM pathway

“…The nanoscale self-assembly properties of small molecule drugs are important in tumor-targeting therapy [ 49 , 50 ], and drug delivery systems based on TF/TFR are important [ 51 ]. The dual-targeting nanoscale self-assembled ruthenium complex 2b was designed to compensate for the shortcomings of low solubility and poor targeting of carbolines.…”