In vitro anticoagulant activity of selected medicinal plants: potential interactions with warfarin and development of new anticoagulants

Abstract

Objectives Warfarin is the most widely used anticoagulant in the world, but it has several limitations including its narrow therapeutic range, need for dose adjustment and high potential for interactions. The simultaneous use of other drugs or even medicinal plants and certain foods could interfere with its therapeutic activity. In this context, this study aims to investigate the in vitro anticoagulant potential and phytochemical constitution of 17 plants selected from a previous clinical cross-sectional study (2014), that investigated the habits of plant utilization among patients taking warfarin. Methods Ethanol extracts and essential oils were evaluated, in vitro, as to their effect in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Four species that presented aPTT >50 s were selected for phytochemical evaluation. Results Thirteen of the 17 plants selected demonstrated a significant anticoagulant effect in at least one of the evaluated parameters. Citrus sinensis (PT=14.75 and aPTT=53.15), Mentha crispa (aPTT=51.25), Mikania laevigata (PT=14.90 and aPTT=52.10), and Nasturtium officinale (aPTT=50.55) showed greater anticoagulant potential compared to normal plasma pool (PT=12.25 and aPTT=37.73). Chemical profiles of these four species were obtained, and certain compounds were identified: rosmarinic acid from M. crispa and isoorientin from N. officinale. Conclusions Thus, the results of this study could be a useful indicator for clinical practice towards the possibility of interaction between these plants and anticoagulants, although further clinical research is needed taking into consideration the limitations of in vitro studies. These findings also suggest that further research into the action of these plants could be of real clinical value in identifying potential alternative anticoagulant therapies.

Anticoagulant and antiplatelet activity of aqueous extracts of Citrus sinensis and Lippia alba: interactions and potential for the development of antithrombotics

“…Thus, the ethanolic extract of both species is more interesting for the potential development of an antithrombotic. Furthermore, these results reinforce the possibility of interaction of these medicinal plants with antithrombotics demonstrated in previous studies that were carried out only with the ethanolic extracts of these species [2,3]. Therefore, it is important to emphasize that the infusion and decoction of these species should be used with caution by patients using anticoagulants and/ or antiaggregants.…”

“…2). Both classes of substances have been linked to anticoagulant, antiplatelet and also anti-inflammatory activities [3,[5][6][7]19]. This, together with the in-vitro results of coagulation and platelet aggregation tests, corroborate to the potential of these medicinal plants for the development of antithrombotics.…”

Molecular Interaction Studies and Phytochemical Characterization of Mentha pulegium L. Constituents with Multiple Biological Utilities as Antioxidant, Antimicrobial, Anticancer and Anti-Hemolytic Agents

“…At 75 μg/mL of M. pulegium extract, PT and APTT were at 26.7 s and 67.8 s, respectively. Recently Leite et al [ 53 ] studied the anticoagulant activity of numerous plants, among which Mentha crispa (APTT = 51.25) showed greatest anticoagulant potential. Ku and Bae [ 54 ] suggested that the inhibition of intrinsic and common pathways was associated with the prolongation of APTT, while the inhibition of the extrinsic coagulation pathway was associated with the prolongation of PT.…”

Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

“…VEGF is commonly expressed in astrocytes, neurons, and endothelial cells (Hayashi et al, 1997;Margaritescu et al, 2011). and can play a neuroprotective role in ischemic stroke (Shim and Madsen, 2018).…”

“…However, VEGF can also increase BBB permeability by destroying the TJ protein of the BBB (Argaw et al, 2009). During cerebral ischemia or trauma, immunohistochemistry showed that expression of the VEGF protein was up-regulated (Sköld et al, 2005;Margaritescu et al, 2011). The VEGF monoclonal antibody, bevacizumab, has been shown to reduce brain edema and improve symptoms caused by radiation-induced brain necrosis in patients undergoing brain tumor resection (Fraum et al, 2011).…”