Metabolomic fingerprinting of Cissampelos sympodialis Eichler leaf extract and correlation with its spasmolytic activity

Abstract

Ethnopharmacological relevanceCissampelos sympodialis Eichler (Menispermaceae) is popularly used in northeastern Brazil for the treatment of respiratory diseases such as bronchitis and asthma. Despite many pre-clinical pharmacological studies, the compounds mediating the anti-asthma activity of polar extracts of Cissampelos sympodialis leaves have not been definitively identified. Aim of the studyAim of the study: The aim of the study was to investigate the correlation between the bioactivity of polar extracts prepared from the leaves of C. sympodialis and the chemical composition using a 1H-NMR-based metabolomics approach. Material and methodsThe metabolic profile of the leaf polar extract during different phenological stages of the plant was investigated using 1H NMR spectroscopy while simultaneously screening for spasmolytic activity using guinea-pig tracheal preparations. The content of the alkaloids previously implicated in the bioactivity of Cissampelos sympodialis was determined by HPLC. ResultsPCA analysis of the 1H NMR data discriminated the extracts from different plant phenological stages. The contents of the major alkaloids decrease (from 2 ± 0.32 μg/mL for warifteine and 1 ± 0.14 μg/mL for methylwarifteine) to undetectable levels from 90 (CsL90 extract) and 120 (CsL120) days onwards for warifteine and methylwarifteine, respectively. All six extracts relaxed the trachea pre-contracted with carbachol, but the CsF210 extract was more potent (EC50 = 74.6 ± 7.9 μg/mL) compared to both CsL90 extracts and CsL180 in the presence of functional epithelium. PLS regression analysis of 1H-NMR spectral data demonstrated that the spasmolytic activity was better correlated with signals for flavonol derivatives. ConclusionsOur data challenge the idea that warifteine and methylwarifteine mediate the spasmolytic activity of the polar extract of C. sympodialis leaves.