Pharmacokinetics and biodistribution of eriocitrin in rats

Authors: FERREIRA, PAULA S. - Universidade Estadual Paulista (UNESP); Manthey, John; NERY, MARINA S. - Universidade Estadual Paulista (UNESP); CESAR, THAIS B. - Universidade Estadual Paulista (UNESP)

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2021
Publication Date: 2/3/2021
Citation: Ferreira, Paula S., Manthey, J.A., Nery, Marina S., Cesar, Thais B. 2021. Pharmacokinetics and biodistribution of eriocitrin in rats. Journal of Agricultural and Food Chemistry. 10.1021. https://doi.org/10.1021/acs.jafc.0c04553.
DOI: https://doi.org/10.1021/acs.jafc.0c04553

Interpretive Summary: A summary of the vibrational energies in the IR spectra of eriocitrin metabolites are shown in Table 2, and gives further evidence of their proposed structures. The presence of glucuronic acid substituents in all of metabolites of eriocitrin were confirmed by the presence of hydroxy groups (OH), exhibited by broad, intense peaks after 3000 cm-1. Also, vibrations from 2956 to 2847 cm-1 indicated the presence of glucuronic acid substituents due to the presence of alkanes (C-H), primarily due CH2 groups in the middle ring of the flavanone. The aromatic ketonic carbonyl groups (C=O) from flavanone skeleton were represented by the presence of peaks between 1609 and 1642 cm-1. Furthermore, the presence of aromatic vibrations (C=C) and of aliphatic and conjugated ethers (C-O) were confirmed by peaks from 1500 to 1580 cm-1, and peaks from 1060 to 1291 cm-1, respectively.21-23 The 1H NMR spectra of the glucuronidated metabolites (Table 3) are consistent with the identifications given to these compounds. The 1H NMR spectrum indicated ERD-7-O-Gluc and ERD-3'-O-gluc had an eriodictyol as their aglycone. The dH signals from H-2', H-5' and H-6' in these compounds are characteristic of the 3,4-disubstituted B-ring of eriodictyol, while the absence of dH signals from H-3' and H-4' at the analyzed range suggest OH substitutes at these positions. hERD-7-O-Gluc, hERD-4'-O-gluc, HESP-7-O-Gluc, and HESP-3'-O- gluc presented similar dH signals from H-2', H-5' and H-6', whereas the -OCH3 signals at H-4', characteristic of homoeriodictyol and hesperetin were observed at their spectrum. The multiplets around 3.20 ppm from H-2", H-3" and H-4" were also observed for the 6 compounds, suggesting the presence of glucuronidation. Interpretations of the aromatic proton resonances are based on earlier published NMR spectra of eriocitrin, eriodictyol, homoeriodictyol, and hesperetin,24,25 and running NMR of authentic standards.

Technical Abstract: Eriocitrin plays a role in the reduction of oxidative stress and inflammation linked to the development of diabetes mellitus and atherosclerosis. We investigated the pharmacokinetics and distribution of eriocitrin metabolites in rats orally administered with eriocitrin. Plasma, urine and organs were collected at 12 different time-points from 0 to 24 hours, and analyzed by HPLC-PDA-MS. For the first time the metabolism and distribution of orally administered eriocitrin were shown. Nine metabolites of eriocitrin were identified in rat urine, and seven in various tissues (eriodictyol, homoeriodictyol, hesperetin and glucuronidated metabolites), and preliminary identifications of these metabolites are suggested. Overall, eriocitrin metabolites were widely distributed in the rat tissues, where homoeriodictyol and homoeriodictyol-7-O-glucuronide were the major metabolites. The half-lives of the metabolites in plasma were between 3 and 3.2 hours and the total bioavailability of eriocitrin was less than 1 %.