Pomolic Acid Isolated from the Leaves of Licania pittieri Inhibits ADP-and Epinephrine-Induced Platelet Aggregation and has Hypotensive Effect on Rats

Estrada, Omar; Alvarado-Castillo, Claudia; Fernandez, AC; López, Miguel Ángel Ramírez; Romero-Vecchione, Eduardo; Vasquez, J Cabezas; Méndez, José D.; Conde, Diego; Cardozo, Alfonso

doi:10.2174/157340709789054786

Cited by 12 publications

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“…In the present study, none of the flavonoids isolated from L. cruegeriana had cardiovascular effects in SHR and only two triterpenoids 5 and 6 showed significant reduction in MABP (60.1% and 17.2% respectively) inducing an elevation in HR (11.0% and 41.2% respectively) as shown in Table 1. A simple structure–activity relationship analysis of these data would suggest that when triterpenoids increase their oxidation state by introducing a hydroxyl group, it seems to be sufficient to significantly increase their hypotensive properties, which is in concordance with what is reported for triterpenoids such as pomolic acid [23] and ursolic acid [24]. On the other hand, one flavonoid (compound 3 ) and three triterpenoids (compounds 4 , 5 and 6 ) were able to inhibit the aggregation of human platelets induced by AA, collagen and ADP as shown in Table 2.…”

Section: Discussionsupporting

confidence: 86%

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

et al. 2014

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Three new lupane-type triterpenoids: 6β,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6β,30-dihydroxybetulinic acid (5) and 6β-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, including IR, ESIMS, 1D-and 2D-NMR experiments, as well as by comparison of their spectral data with those of related compounds. All compounds were evaluated in vivo for their effects on the mean arterial blood pressure (MABP) and heart rate (HR) of spontaneously hypertensive rats (SHR) and also in vitro for their capacity to inhibit the human platelet aggregation. None of the isolated flavonoids 1-3 showed cardiovascular effects on SHR and among the isolated triterpenoids 4-9 only 5 and 6 produced a significant reduction in MABP (60.1% and 17.2%, respectively) and an elevation in HR (11.0% and 41.2%, respectively). Compounds 3, 4, 5 and 6 were able to inhibit human platelet aggregation induced by ADP, collagen and arachidonic acid with different selectivity profiles.

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Section: Discussionsupporting

confidence: 86%

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

et al. 2014

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“…In a noteworthy study, it is reported that PA proved to be a potent inhibitor of epinephrine-induced human platelet aggregation (IC 50 20 nM) [30]. These were the first results to show the anti-aggregating effects of PA, suggesting its potential role in cardiovascular therapy.…”

Section: +mentioning

confidence: 86%

“…Therefore, it may be possible to elucidate the effect of PA on epinephrine-induced platelet activation, assuming that PA does not influence serotonin-induced PSC. Estrada et al [30] also reported that PA does not affect aggregation induced by several agonists (e.g. platelet-activating factor, collagen, U46619 (a thromboxane A 2 analogue) and arachidonic acid).…”

Section: +mentioning

confidence: 98%

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Plant extracts inhibit ADP-induced platelet activation in humans: their potential therapeutic role as ADP antagonists

Jagroop

2013

Purinergic Signalling

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Adenosine diphosphate (ADP) plays a pivotal role in platelet activation. Platelet hyperactivity is associated with vascular disease and also has a key role in haemostasis and thrombosis. ADP activates platelets through three purinoceptor subtypes, the G q -coupled P2Y 1 receptor, G icoupled P2Y 12 receptor and P2X 1 ligand-gated cation channel. Platelet ADP purinergic receptors are therefore suitable targets for antiplatelet drugs. Thienopyridines such as clopidogrel and ticlopidine, as well as other ADP receptor antagonists like prasugrel, ticagrelor, cangrelor and elinogrel have demonstrated clinical benefits via the inhibition of the selective purinergic ADP receptor, P2Y 12 . However, they still have limitations in their mode of action and efficacy, like increased risk of bleeding. Thus, the ongoing pursuit to develop newer and more effective antiplatelet agents continues. There is a growing interest in the purinergic antiplatelet properties exhibited by plant extracts. This article considers the following: pomolic acid isolated from Licania pittieri, brazilin isolated from the heartwood of Caesalpinia sappan L, phylligenin isolated from the twigs of Muraltia vulpina , bark oil of Gonystylus velutinus , seed and bark extracts from Aesculus hippocastanum L . and red wine phenolics and catechins isolated from green tea. Moreover, the method used to investigate platelet purinergic receptors should be considered, since using a more sensitive, highresolution platelet sizer can sometimes detect platelet variations when the light transmission method was not able to do so. The exact mechanisms by which these plant extracts work need further investigation. They all however inhibit ADP-induced activation in human platelets. This could explain, at least in part, the protective effect of plant extracts as antiplatelet agents.

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“…Platelet aggregation was monitored using Born’s turbidimetric method [ 16 ]. Inhibition experiments were done as described earlier [ 17 ] by incubating the platelets with different A. purpurea samples, norpurpureine and purpureine for 10 min before stimulation with the agonists: 10 μM ADP, 1 μg/ml collagen (in PRP) and 0.075 U/ml thrombin (in WP). DMSO was used as a vehicle at a final concentration less than 0.25% in all the cases.…”

Section: Methodsmentioning

confidence: 99%

The norpurpureine alkaloid from Annona purpurea inhibits human platelet activation in vitro

et al. 2018

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BackgroundThe leaves of Annona purpurea have yielded several alkaloids with anti-aggregation activities against rabbit platelets. This is promising in the search for agents that might act against platelets and reduce the incidence of cardiovascular diseases. Since significant differences in platelet function have been reported between human and animal platelets, a study focusing on the effect of A. purpurea extracts against human platelet activation is necessary.MethodsThe compounds in an A. purpurea ethanolic extract underwent bio-guided fractionation and were used for in vitro human platelet aggregation assays to isolate the compounds with anti-platelet activity. The bioactive compounds were identified by spectroscopic analysis. Additional platelet studies were performed to characterize their action as inhibitors of human platelet activation.ResultsThe benzylisoquinoline alkaloid norpurpureine was identified as the major anti-platelet compound. The IC50 for norpurpureine was 80 μM against platelets when stimulated with adenosine 5′-diphosphate (ADP), collagen and thrombin. It was pharmacologically effective from 20 to 220 μM. Norpurpureine (220 μM) exhibited its in vitro effectiveness in samples from 30 healthy human donors who did not take any drugs during the 2 weeks prior to the collection. Norpurpureine also gradually inhibited granule secretion and adhesion of activated platelets to immobilized fibrinogen. At the intra-platelet level, norpurpureine prevented agonist-stimulated calcium mobilization and cAMP reduction. Structure–activity relationship analysis indicates that the lack of a methyl group at the nitrogen seems to be key in the ability of the compound to interact with its molecular target.ConclusionNorpurpureine displays a promising in vitro pharmacological profile as an inhibitor of human platelet activation. Its molecular target could be a common effector between Ca2+ and cAMP signaling, such as the PLC-PKC-Ca2+ pathway and PDEs. This needs further evaluation at the protein isoform level.Electronic supplementary materialThe online version of this article (10.1186/s11658-018-0082-4) contains supplementary material, which is available to authorized users.

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Pomolic Acid Isolated from the Leaves of Licania pittieri Inhibits ADP-and Epinephrine-Induced Platelet Aggregation and has Hypotensive Effect on Rats

Cited by 12 publications

References 0 publications

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

Plant extracts inhibit ADP-induced platelet activation in humans: their potential therapeutic role as ADP antagonists

The norpurpureine alkaloid from Annona purpurea inhibits human platelet activation in vitro

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