Abstract
<title>Abstract</title> <p> <italic>Terminalia arjuna</italic> bark ethanolic extract and its bioactive compound, arjunetin, possess diverse therapeutic properties, including anti-inflammatory, anti-diabetic, anti-cancer, anti-malarial, and anti-viral activities. This study developed a novel solvent extraction-based method for isolating arjunetin from <italic>T. arjuna</italic> bark, achieving 95% purity without column chromatography. The isolated arjunetin and direct ethanolic extract (DEE) were evaluated for anti-inflammatory, anti-diabetic, anti-cancer, and cytotoxic activities. Arjunetin demonstrated significant anti-inflammatory activity by reducing nitric oxide production in LPS-stimulated cells, while the ethanolic extract showed 42.4% inhibition at 100 µg/mL. In anti-diabetic assays, arjunetin (0.730–2.289 µg/mL) induced a dose-dependent enhancement of glucose uptake. Similarly, the direct ethanolic extract (DEE) significantly improved glucose utilization in differentiated 3T3-L1 adipocytes, increasing glucose uptake from 56.81% in the insulin-treated control to 72.33% at 100 µg/mL. These findings suggest that both arjunetin and DEE exert potent insulin-sensitizing effects by enhancing insulin-mediated glucose transport, highlighting their promising therapeutic potential for diabetes management. Arjunetin exhibited potent anticancer activity against MCF-7 cells with an IC₅₀ of 10.807 µg/mL, whereas the extract showed cytotoxicity against MDA-MB-231 cells (IC₅₀ 84.316 µg/mL). Cytotoxicity studies on Vero cells indicated lower toxicity of the extract toward normal cells. These findings validate the traditional medicinal use of <italic>T. arjuna</italic> and highlight arjunetin as a promising therapeutic candidate for inflammation, cancer, and diabetes management. </p>