Affiliation:
1. Department of Physiology, Faculty of Medicine, Eskisehir Osmangazi University, 26040, Eskisehir, Turkey
2. Department of Mathematics and Science Education, Faculty of Education, Kırıkkale University, Yahşihan, 71450, Kırıkkale, Turkey
3. Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir,
Turkey
Abstract
Aims:
Flavonoids naturally exist in plants as secondary metabolites. In this study, the
aim is to determine and compare the theoretical and in vivo chemical activities of 7,8-
dihydroxyflavone (7,8-DHF) and 4'dimethylamino-7,8-dihydroxyflavone (4’-DMA-7,8-DHF),
tyrosine receptor kinase B (TrkB) receptor agonist flavonoid molecules with reported potent neuroprotective
effects.
Methods:
The density functional theory (DFT) (RB3LYP) method was used for the theoretical
chemical analysis. For the in vivo studies, 6-month-old Wistar rats were used in two groups
(n=8). 7,8-DHF and 4’-DMA-7,8-DHF (5 mg/kg) were administered intraperitoneally (ip) to
each group. Then, plasma samples were collected by carotid catheterization, and brain samples
by the microdialysis technique were collected simultaneously for 12 h from awake rats. The level
of 7,8-DHF and 4’-DMA-7,8-DHF in blood and brain samples were analyzed and their pharmacokinetics
were determined.
Results:
Theoretical calculations show that 7,8-DHF is slightly more stable than 4’-DMA-7,8-
DHF. The in vivo pharmacokinetic results show that the maximum concentration of 7,8-DHF was
about 48 ng/mL, whereas it was only 8 ng/mL for 4’-DMA-7,8-DHF.
Conclusion:
Our results suggest that the 4'-DMA-7,8-DHF is more unstable and is more prone to
binding to TrkB than 7,8-DHF. On the other hand, the in vivo pharmacokinetic results show that
7,8-DHF is more stable than 4’-DMA-7,8-DHF when it is applied systemically at therapeutic
concentrations.
Funder
Eskisehir Osmangazi University Scientific Research Projects Committee
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Molecular Medicine,Biochemistry,Biophysics