Interaction Metabolomics to Discover Synergistic Constituents of Magnolia officinalis

Abstract Identifying combinations of molecules responsible for the biological activity of mixtures has long been a challenge for researchers in the natural products sciences. Recently, interaction metabolomics was described as a strategy for overcoming this problem. Herein, we sought to demonstrate how interaction metabolomics might be employed to identify a synergist from a sample that was not known to contain one at the onset of the study. The test case employed was an extract from the bark of the plant Magnolia officinalis, which contains the antimicrobial lignans magnolol (1) and honokiol (2). The extract was subjected to several rounds of chromatographic purification, and a set of sub-fractions were spiked with a sub-inhibitory concentration of magnolol and analyzed by liquid chromatography coupled to mass spectrometry (LC−MS). In parallel, the antimicrobial activity of the fractions was tested against a clinically relevant strain of methicillin-resistant Staphylococcus aureus (MRSA). Using interaction metabolomics, we identified a fatty acid (3, coriolic acid) from one of the fractions that synergistically enhances the antimicrobial activity of magnolol against MRSA. This study demonstrates an approach that can employed by other researchers seeking to identify synergists in biologically active natural product extracts.