Chitosan-functionalized Ajuga integrifolia-mediated zinc oxide nanoparticles for antidiabetic and anti-inflammatory applications: An integrated In Vitro, In Vivo, and In Silico study.

Diabetes mellitus is a chronic metabolic disease characterized by high blood glucose levels (BGL), while inflammation is an adaptive physiological response which is triggered by adverse conditions, including infection and tissue damage. In the present study, Ajuga integrifolia (AI) mediated zinc oxide nanoparticles (AI-ZnO NPs) were prepared and functionalized with chitosan (CS). The synthesized AI-ZnO and CS-ZnO NPs were characterized using advanced techniques. UV-Visible spectroscopic analysis showed a prominent peak of AI-ZnO at 361 nm, which blue-shifted to 347 nm with CS coating. Functional groups were identified using Fourier transform infrared spectroscopy (FTIR), while particle morphology and size were characterized using field-emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS). X-ray Diffraction (XRD) confirmed the hexagonal wurtzite structure. Laminin, AMP-activated protein kinase (AMPK), Islet Amyloid Polypeptide (IAPP), and alpha-glucosidase were docked with chitosan, yielding distinct binding energies as well as varying interaction residues, interaction types, and distances. The in vitro antidiabetic and anti-inflammatory assays showed considerable potential, with inhibition ranging from 12.1 ± 2.01% to 89.46 ± 0.77%. The in vivo antidiabetic and anti-inflammatory experiments were performed in a murine model. BGL increased markedly from the normal baseline (95 mg/dl) to about 224 mg/dl within 24 h of alloxan administration. 40 mg/kg of CS-ZnO showed the highest potential, lowering the BGL to 121 ± 2 mg/dl. The ear edema decreased from 0.35 mm to 0.26 mm with 40 mg/kg of CS-ZnO. The histopathological images also confirmed the medicinal potential of the test samples, which may serve as alternative medicinal agents in the future.