Diabetes mellitus (T2DM) is a multifaceted metabolic
disorder with
no definite treatment. In silico characterization can help to explain
the interaction between molecules and predict 3D structures. The aim
of the present study was to evaluate the hypoglycemic activities of
the hydro-methanolic extract of Cardamine hirsuta in a rat model. In vitro antioxidant and α-amylase inhibitory
assays were evaluated in the present study. Phyto-constituents were
quantified using RP-UHPLC-MS analysis. Molecular docking of compounds
into the binding site of different molecular targets, i.e., tumor
necrosis factor (TNF-α), glycogen synthase kinase 3 β
(GSK-3β), and AKT, was carried out. Acute toxicity model, in
vivo antidiabetic effect, and the influence on biochemical and oxidative
stress parameters were also investigated. T2DM was induced in adult
male rats by streptozotocin using a high-fat diet model. Three different
doses (125, 250, and 500 mg/kg BW) were orally gavaged for 30 days.
Mulberrofuran-M and quercetin3-(6″caffeoylsophoroside) have
demonstrated remarkable binding affinity toward TNF-α and GSK-3β,
respectively. 2,2-Diphenyl-1-picrylhydrazyl and α-amylase inhibition
assay exhibited IC50 values of 75.96 and 73.66 μg/mL, respectively.
In vivo findings exhibited that 500 mg/kg body weight (BW) dose of
the extract significantly decreased the blood glucose level, improved
biochemical parameters as well as oxidative stress by reduction of
lipid peroxidation, and increased high-density lipoproteins. Moreover,
activities of glutathione-s-transferase, reduced glutathione, superoxide
dismutase were enhanced, and cellular architecture in the histopathological
examination was restored in treatment groups. The present study affirmed
the antidiabetic activities of mulberrofuran-M and quercetin3-(6″caffeoylsophoroside)
present in the hydro-methanolic extract of C. hirsuta, possibly due to the reduction in oxidative stress and α-amylase
inhibition.