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

O.      Estrada; C.      Alvarado-Castillo; A.   Z.   Fernandez; M.      Lopez; E.      Romero-Vecchione; J.      Vasquez; J.      Mendez; D.      Conde; A.      Cardozo

Abstract

Several Chrysobalanaceae family members are considered medicinal plants in South America and their infusions have been widely used to treat several diseases, such as diabetes and hypertension. Methanolic extract from the leaves of Licania pittieri (Chrysobalanaceae), has previously shown hypotensive effect in anaesthetized normotensive rats. The aim of this study was to identify the compounds present in the methanolic extract of L. pittieri that could be responsible for the hypotensive effect. Bioactivity-guided fractionation of this extract was done by monitoring the changes induced on mean arterial blood pressure and heart rate on normotensive rats, which led to the isolation of three known compounds identified by NMR spectroscopy methods as pomolic acid, quercetin and astilbin. Pomolic acid (0.4 mg/kg, i.v.) diminished mean arterial blood pressure (24.1 %) for more than 45 minutes and also heart rate (38.7 %), while quercetin and astilbin (4 mg/Kg each, i.v.) showed a weak and transient hypotensive effect. In addition, the observation of nose bleeding in pomolic acid-treated rats led us to investigate its effects on hemostasis. Pomolic acid proved to be a potent inhibitor of the aggregation of human platelets induced by ADP and Epinephrine, exhibited IC50 values close to 60 nM and 20 nM, respectively. In contrast, pomolic acid did not inhibit human platelet aggregation induced by PAF, collagen, U46619 (thromboxane analogue), TRAP or arachidonic acid. These results showed for the first time the hypotensive and platelet anti-aggregating effects of pomolic acid and suggested its potential role in cardiovascular therapy.

Keywords: Licania pittieri, triterpenoids, pomolic acid, flavonoids, cardiovascular screening, platelets