Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde

Cinnamon is one of the oldest known spices used in various food delicacies and herbal formulations. Cinnamaldehyde is a primary active constituent of cinnamon and substantially contributes to the food additive and medicinal properties of cinnamon. This report deals with cinnamaldehyde bioaccessibility, metabolic clearance, and interaction with human xenobiotic receptors (PXR and AhR). Results showed the bioaccessibility of cinnamaldehyde was 100 % in both fasted and fed-state gastric and intestinal fluids. Upon incubation with human liver microsomes (HLMs) and human liver S-9 fraction, cinnamaldehyde (alone or in cinnamon oil) rapidly oxidized into cinnamic acid. Cinnamon oil dose-dependently activated AhR in human AhR-reporter cells, but cinnamaldehyde and cinnamic acid did not affect AhR. In addition, cinnamon oil and cinnamic acid dose-dependently activated PXR in human hepatic (HepG2) and intestinal (LS174T) cells. Both cinnamon oil and cinnamaldehyde inhibited the catalytic activity of CYP2C9 and CYP1A2. Our findings indicated that cinnamaldehyde (alone or in cinnamon oil) possesses high bioaccessibility and adequate metabolic stability. Hence, while controlled ingestion of cinnamon-containing foods or supplements may have beneficial effects but overconsumption could induce PXR or AhR-dependent herb-drug interactions (HDIs) which can bring deleterious effects on human health, particularly in individuals with chronic health conditions.