Quercetin and Kaempferol as Multi-Targeting Antidiabetic Agents against Mouse Model of Chemically Induced Type 2 Diabetes

Abstract

Finding effective, safe medications that address several aspects of the metabolic condition known as diabetes is an urgent
medical need. The potential of quercetin and kaempferol as multi-targeting antidiabetic agents was examined in this research. Using
pharmacokinetic and docking software (AutoDock Vina 1.1.2), the druggability and binding affinities towards several antidiabetic
targets were investigated for both drugs. According to our research, quercetin and kaempferol have good ADMET (absorption,
distribution, metabolism, excretion, and toxicity) profiles and follow Lipinski's rule of five. In comparison to metformin, the positive
control, both compounds exhibited stronger binding affinities for C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium-glucose cotransporter-1 (SGLT-1). Kaempferol reduced α-amylase activity (in vitro) to a degree of 37.43 ± 0.42% and quercetin to a degree of
20.30 ± 0.49. In diabetic mice caused by streptozotocin-nicotinamide (STZ-NA), their oral supplementation led to a substantial decrease
in blood glucose levels (p < 0.001), an improvement in lipid profile (p < 0.001), and an enhancement in total antioxidant status (p <
0.01). In addition, the growth of cancer cells Huh-7 and HepG2 was considerably reduced by both compounds (p < 0.0001), but the
viability of the non-cancer Vero cell line was unaffected. Finally, compared to metformin, quercetin and kaempferol had stronger
binding affinities to a variety of targets. Both compounds show promise for future research in diabetes treatment due to their antidiabetic
capabilities in vitro and in vivo, as well as their anticancer activity. Maybe since they both target the same receptors, the two medications
did not work together synergistically.