Cinnamon is an aromatic bark derived from the Cinnamomum verum tree, used in various food products and traditional herbal medicines. It adds flavors to snacks, cereals, hot chocolates, and teas. Cinnamon bark typically contains cinnamon oil (1-4%), trans-cinnamaldehyde (65-80%), eugenol (5-10%), and trans-cinnamic acid (5-10%). This cinnamon oil contains many compounds, mainly cinnamaldehyde. This cinnamon oil helps to manage blood circulation, liver function, and blood glucose regulation. The health effects of cinnamon oil and cinnamaldehyde are well explained in many studies. However, there is limited scientific evidence available regarding how the body absorbs these compounds, how they are metabolized, and how they interact with human xenobiotic receptors in the liver and intestinal systems, which are important for their effectiveness and safety. These aspects are explained in a recent study published in Food Chemistry: Molecular Sciences.
This study assessed the bioaccessibility of cinnamaldehyde by using simulated gastric fluids and simulated intestinal fluids. The fasted state simulated gastric fluid (FaSSGF) had a pH of 1.65, and the fed state simulated gastric fluid (FeSSGF) had a pH of 4.52. The fasted state simulated intestinal fluid (FaSSIF) had a pH of 6.45, and the fed state simulated intestinal fluid (FeSSIF) had a pH of 4.92. Key metabolic parameters like metabolic half-life (T1/2) and intrinsic clearance (CLint) were assessed by using human liver S-9 fraction and human liver microsomes (HLMs). Additionally, the interaction of cinnamic acid, cinnamaldehyde, and cinnamon oil with PXR and aryl hydrocarbon receptor (AhR) human xenobiotic receptors was studied by using human hepatic (HepG2) and intestinal (LS174T) cellular models. This study employed several methods, such as cytochrome P450 (CYP) inhibition assay, cell viability assay, luciferase reporter gene assay for PXR activation, AhR reporter gene assay, and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis.
This study found that cinnamaldehyde concentrations were 270 ± 20 μg/mL in FaSSGF and 300 ± 30 μg/mL in FeSSGF. In simulated intestinal fluids, concentrations were 320 ± 30 μg/mL in FaSSIF and 320 ± 40 μg/mL in FeSSIF. These results suggest that cinnamaldehyde exhibits similar stability and bioaccessibility in both fed and fasted states under intestinal and gastric conditions.
Cinnamaldehyde (>90%) was metabolized in 10 mins with a T1/2 of 4.84 ± 0.05 min and CLint of 143.30 ± 0.12 mL/min/kg in the presence of HLMs. Cinnamaldehyde was metabolized similarly to that of HLMs during liver S-9 fraction-mediated metabolism, with a T1/2 of 1.97 ± 0.07 minutes and a CLint of 358.32 ± 14 mL/min/kg. In the presence of HLMs, negative controls showed no significant change in the stability of cinnamaldehyde and cinnamic acid after 120 minutes of incubation time, whereas the positive control (testosterone) reported a T1/2 of 19.30 ± 0.11 minutes and a CLint of 35.83 ± 0.10 mL/min/kg. The stability of cinnamaldehyde was similar when the liver S9 fraction was treated with cinnamon oil.
A 100 μg/mL concentration of cinnamic acid, cinnamon oil, and cinnamaldehyde had a marginal effect on cell viability. Cinnamon oil and cinnamaldehyde concentration did not affect the activity of PXR in HepG2 cells, whereas cinnamic acid increased this activity in a dose-dependent manner, showing >3-fold activation at the highest concentration of 20 μg/mL. In LS174T cells, cinnamaldehyde had no inductive effect on PXR, whereas both cinnamic acid and cinnamon oil activated >3-fold at 20 μg/mL. Additionally, cinnamon oil dose-dependently activated AhR in human AhR-receptor cells (12.82-fold at 20 μg/mL), but cinnamaldehyde and cinnamic acid did not affect AhR. The activities of CYP1A2 and CYP2C9 were mildly inhibited by cinnamon oil and cinnamaldehyde.
In conclusion, cinnamaldehyde derived from cinnamon oil is highly bioaccessible and rapidly metabolized into cinnamic acid. It exhibits moderate activation of the PXR and AhR, and weak inhibition of CYP1A2 and CYP2C9. Hence, although limited use of cinnamon extract may have health advantages, long-term use may increase the risk of herb-drug interactions. Further clinical research will be needed to investigate this hypothesis.
