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

Cissampelos 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 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.

The 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.

PCA 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.

Our data challenge the idea that warifteine and methylwarifteine mediate the spasmolytic activity of the polar extract of C. sympodialis leaves.