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Background: The rhizome of Zingiber officinale or ginger shows its potential against oxidative stress, microbial infections, and managing diabetes mellitus. Method: Chemical reagents and plant materials of analytical grade were procured. Aqueous extract of Zingiber officinale rhizome was prepared through maceration. FT-IR, heavy metal detection, UV-VIS spectroscopy, and carbohydrate estimation were performed. Antimicrobial activity against bacterial and fungal strains was evaluated using agar diffusion method. Total polyphenol, flavonoid, and flavonol contents were quantified. Antioxidant activity was assessed using DPPH, reducing power, and FRAP assays. Antidiabetic activity was determined by α-amylase and α-glucosidase inhibition. Cytotoxicity, glucose uptake, and antiglycation assays were conducted on L6 cells. Blood compatibility was tested on human RBCs. Results: The analysis showed total phenolic content (TPC) at 27.9±0.27 mg/g GAE, total flavonoid content (TFC) at 18.4 mg/g QE, and total flavonol content (TFolC) at 41.1±4 mg/g QE. The extract demonstrated potent antioxidant activity with IC50 values of 353 µg/mL (DPPH), 600 µg/mL (H2O2 scavenging), and displayed antidiabetic effects inhibiting α-amylase (IC50=1564.43 µg/mL) and α-glucosidase (IC50=581.4 µg/mL). Cytotoxicity assays yielded an IC50 of 533.3 µg/mL (NRU assay) and highest glucose uptake at 254.74±62.79 µg/mL (L6 cells). The extract showed minimal hemolytic activity (-0.305±0.031%) and high cell viability (99%). In silico docking revealed strong interactions with targeted proteins. Conclusion: In conclusion, the aqueous extract of Zingiber officinale rhizome exhibits diverse pharmacological activities including antioxidant, antimicrobial, antidiabetic, and antiglycation properties, along with notable bio-safety and cytotoxicity profiles.
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