Untargeted metabolomics based prediction of therapeutic potential for apigenin and chrysin

Flavonoids belong to the polyphenol superfamily and present in our foods derived from natural sources including fruits and vegetables. Apigenin and Chrysin, prominent flavonoids have been demonstrated to have systemic benefits. Our previous work was first to establish the impact of apigenin and chrysin on cellular transcriptome. In the current study, we have revealed the ability of apigenin and chrysin to alter cellular metabolome based on untargeted metabolomics. Based on our metabolomics data, both these structurally related flavonoids demonstrate diverging and converging properties. Apigenin demonstrated the potential to possess anti-inflammatory and vasorelaxant properties through the upregulation of alpha-linolenic acid and linoleic acid metabolism intermediates. Chrysin on the other hand exhibited abilities to inhibit protein and pyrimidine synthesis along with downregulation of gluconeogenesis pathways based on the metabolites obtained. These metabolic effects were due to the impact of chrysin to modulate L-alanine metabolism and urea cycle. On the other hand, both the flavonoids demonstrated converging effects by their ability to downregulate metabolites involved in cholesterol biosynthesis and uric acid synthesis namely 7-dehydrocholesterol and xanthosine respectively. Our work could provide understanding regarding the various therapeutic potential of these naturally occurring flavonoids which are food constituents to treat metabolic complications in conditions like obesity, diabetes, cancer, and cardiovascular diseases. Further investigation of these natural agents for targeted diseases using whole animal and translational approaches will validate their therapeutic ability and help in curbing an array of metabolic complications.