Exploring beetroot (Beta vulgaris L.) for diabetes mellitus and Alzheimer's disease dual therapy: in vitro and computational studies

Abstract

This study explored the flavonoid-rich extract of beetroot (Beta vulgaris L.) for type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) dual therapy by using in vitro and molecular simulation studies. Flavonoid-rich extracts of B. vulgaris fruit were evaluated for their antidiabetic and anti-alzheimic activities. Molecular docking and dynamic simulation were performed to identify potential bioactive flavonoids with dual therapeutic effects on T2D and AD. Flavonoid-rich extracts of B. vulgaris fruit (IC₅₀ = 73.062 ± 0.480 μg mL⁻¹) had moderate activity against α-amylase compared to the standard acarbose (IC₅₀ = 27.104 ± 0.270 μg mL⁻¹). Compared with acarbose, flavonoid-rich extracts of B. vulgaris fruit had appreciable activity against α-glucosidase (IC₅₀ = 17.389 ± 0.436 μg mL⁻¹) (IC₅₀ = 37.564 ± 0.620 μg mL⁻¹). For AChE inhibition, flavonoid-rich extracts of B. vulgaris fruit exhibited (p < 0.0001) inhibitory activity (IC₅₀ = 723.260 ± 5.466 μg mL⁻¹), albeit weaker than that of the standard control, galantamine (IC₅₀ = 27.950 ± 0.122 μg mL⁻¹). Similarly, flavonoid-rich extracts of B. vulgaris fruit showed considerable (p < 0.0001) inhibitory effects on BChE (IC₅₀ = 649.112 ± 0.683 μg mL⁻¹). In contrast, galantamine (IC₅₀ = 23.126 ± 0.683 μg mL⁻¹) is more potent than the extracts of B. vulgaris fruit. Monoamine oxidase (MAO) activity increased in FeSO₄-induced brain damage. In contrast, flavonoid-rich extracts of B. vulgaris fruit protected against Fe²⁺-mediated brain damage by suppressing MAO activity in a concentration-dependent manner. HPLC-DAD profiling of the extracts identified quercetrin, apigenin, rutin, myricetin, iso-quercetrin, p-coumaric acid, ferulic acid, caffeic acid, and gallic acid. Molecular docking studies revealed quercetrin, apigenin, rutin, iso-queretrin, and myricetin were the top docked bioactive flavonoids against the five top target proteins (α-amylase, α-glucosidase AchE, BchE, and MAO). Molecular dynamic simulations revealed that the complexes formed remained stable over the course of the simulation. Collectively, the findings support the prospect of flavonoid-rich extracts of B. vulgaris root functioning as a dual therapy for T2D and AD.