Antihyperglycemic effect, antioxidant and dipeptidyl peptidase 4 inhibitory potential of Pteridium acquilinum flavonoids rich extract

The current therapeutic agents for diabetes provide glycemic control but not without adverse effects, necessitating the investigation of safe and effective alternatives. This research investigated the potential of a flavonoid-rich extract of Pteridium aquilinum (PAFRE) in the treatment of diabetes, employing an integrated in silico, in vitro, and in vivo approach. The DPP4 inhibitory potential of PAFRE was studied using an in vitro and in silico model, while the antihyperglycemic effect of PAFRE was studied in an alloxan-induced diabetic rat model. Thirty albino rats randomly assigned to five groups were used and given different treatments: Group 1, normal control; Group 2, diabetes control; Groups 3 and 4, diabetic rats treated with 100 mg/kg b.w. and 200 mg/kg b.w. of PAFRE, respectively; Group 5, diabetic rats treated with glibenclamide (5 mg/kg b.w.) for 14 days. The compounds of PAFRE identified by GC-MS were docked for inhibitory potential against DPP-4 using AutoDock in PyRx and Discovery Studio. In vitro assays revealed that PAFRE possesses potent inhibitory activity against DPPH and DPP-4. The in silico molecular docking supported these findings, showing high binding affinity of identified phytocompounds to the active site of DPP-4, comparable to that of a standard inhibitor (Alogliptin). An in vivo study showed that PAFRE administration significantly (p < 0.05) reduced fasting blood glucose, modulated antioxidant enzyme activities (SOD, CAT, GPx), and suppressed lipid peroxidation (MDA), thereby mitigating oxidative stress while attenuating dyslipidemia, liver enzyme dysfunction, and renal damage. These findings suggest that PAFRE exhibits antidiabetic effects by attenuating oxidative stress and inhibiting DPP-4 activity, highlighting P. aquilinum flavonoids as promising candidates for the development of natural therapeutics for managing diabetes mellitus.