Correlation of chemical composition and anticoagulant activity in different accessions of Brazilian Lippia alba (Verbenaceae)

Abstract

IntroductionLippia alba, popularly known as “cidreira” (lemon balm) is used to treat gastrointestinal disorders, anxiety, and insomnia. However, this species is known for its phenotypic plasticity and genome variation, resulting in variation of the chemical composition that can alter the pharmacological effect. This species was identified as one of the most consumed by patients undergoing warfarin treatment and there are no studies on its safety in concomitant use with anticoagulants. MethodsEthanolic extract from 18 different accessions of L. alba was studied for its anticoagulant activity using a thrombin generation test and for its chemical composition using ultra-efficient liquid chromatography-diode array detector. Hierarchical Cluster Analysis and Principal Component Analysis were performed to analyze the relationship between anticoagulant activity and chemical composition of L. alba accessions. ResultsIn the phytochemical analysis it was possible to identify the presence of flavonoids and phenylpropanoids in all L. alba accessions. Sixteen of them (89 %) were able to reduce thrombin formation compared to the control, but there was a large difference in anticoagulant activity between the accessions. Discussion/conclusionIn general, the most active accessions are diploids while tetraploids were less active. All triploid accessions have compound 1, which is rarely found in diploids and tetraploids. Chemometric analyses demonstrate similarity of chemical composition within accessions of the same ploidy (2x, 3x, 4x) and indicate that the anticoagulant activity is due to the synergism between flavonoids and phenylpropanoids. Therefore, it is important that this plant species be used with caution in patients using oral anticoagulants.