Pharmacokinetic and Permeation Studies in Rat Brain of Natural Compounds Led to Investigate Eugenol as Direct Activator of Dopamine Release in PC12 Cells

Eugenol, cinnamaldehyde and D-limonene, the main components of natural essential oils, are endowed with antioxidant and anti-inflammatory properties which allow them to induce beneficial effects on intestinal, cardiac and neuronal levels. In order to characterize their pharmacokinetic profiles and aptitude to permeate in the central nervous system after intravenous and oral administration to rats, new analytical procedures, easily achievable with HPLC-UV techniques, were developed. The terminal half-lives of these compounds range from 12.4 +/- 0.9 (D-limonene) and 23.1 +/- 1.6 min (cinnamaldehyde); their oral bioavailability appears relatively poor, ranging from 4.25 +/- 0.11% (eugenol) to 7.33 +/- 0.37% (cinnamaldehyde). Eugenol evidences a marked aptitude to permeate in the cerebrospinal fluid (CSF) of rats following both intravenous and oral administrations, whereas cinnamaldehyde appears able to reach the CSF only after intravenous administration; limonene is totally unable to permeate in the CSF. Eugenol was therefore recruited for in vitro studies of viability and time-/dose-dependent dopamine release in neuronal differentiated PC12 cells (a recognized cellular model mimicking dopaminergic neurons), evidencing its ability to increase cell viability and to induce dopamine release according to a U-shaped time-course curve. Moreover, concentration-response data suggest that eugenol may induce beneficial effects against Parkinson's disease after oral administration.

Automated summary

Eugenol, cinnamaldehyde, and D-limonene, the main components of natural essential oils, have antioxidant and anti-inflammatory properties and can have beneficial effects on the intestine, heart, and nervous system. New analytical procedures were developed to study their pharmacokinetics and ability to penetrate the central nervous system in rats. Eugenol showed the highest permeability in the cerebrospinal fluid (CSF), while cinnamaldehyde could only reach the CSF through intravenous administration and limonene had no ability to penetrate the CSF. Eugenol also increased cell viability and induced dopamine release, suggesting potential beneficial effects against Parkinson's disease after oral administration.