Oral bioavailability and neuroprotective effect of a novel food-grade formulation of fisetin using fenugreek-galactomannan hydrogel scaffolds

Abstract

Background

Despite the beneficial pharmacological effects, poor oral bioavailability limits the nutritional efficacy of fisetin, a dietary flavonoid. To this end, herein we report the bioavailability and efficacy of an innovative formulation of fisetin using a fenugreek-galactomannan hydrogel scaffold (FF-20).

Methods

In the first phase of the study, female Wistar rats (n = 42) were randomly divided into two groups (n = 21/group) and orally administered with either unformulated (UF) or FF-20 (50 mg/kg b. wt.) and plasma concentration of fisetin was estimated by UPLC-ESI-MS/MS. In the second phase, the relative influence of FF-20 on alcohol-induced neurotoxicity was followed on animals (n = 24) randomized into four groups, Group I – vehicle control, Group II – ethanol treated, Group III – ethanol+ UF, and Group IV – ethanol + FF-20 and treated at 50 mg/kg b. wt. per day for 14 days.

Results

Area under plasma concentration verses time curve showed 9.83-fold enhancement in bioavailability for FF-20, with significantly enhanced pharmacokinetic parameters (*** P < 0.001). Behavior studies revealed significant improvement in reference memory errors, working memory errors, and anxiety among fisetin-treated animals and the improvement was significant in FF-20, compared to UF (* P < 0.05). Neurotransmitters and gene expressions of NMDAR, MAO A&B, and KLF-11 were altered by alcohol treatment; but were restored/improved in FF-20 group. Histopathology of brain tissues also indicated the reversal of alcohol-induced necrosis and tissue damage by FF-20.

Conclusion

FF-20 enhanced the oral bioavailability and significantly alleviated alcohol-induced neurotoxicity in experimental rats.