Ultrasound-Optimized Extraction and Multi-Target Mechanistic Analysis of Antioxidant and Hypoglycemic Effects of Amomum villosum Essential Oil

<i>Amomum villosum</i>, a medicinal and edible plant, has shown promise in improving digestive health; however, the mechanisms underlying its antioxidant and hypoglycemic effects remain unclear. This study aimed to optimize the extraction of <i>A. villosum</i> essential oil (AVEO) and elucidate its bioactive potential. Ultrasound-assisted extraction yielded 3.84% AVEO under optimal conditions. Gas chromatography-mass spectrometry combined with SwissADME analysis identified nine active components, including bornyl acetate, (-)-Spathulenol, and (-)-Pogostol. In vitro assays demonstrated potent α-glucosidase inhibition (IC₅₀: 0.99 mg/mL) and strong free radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (IC₅₀: 0.87 mg/mL), hydroxyl (IC₅₀: 0.18 mg/mL), and superoxide anion radicals (IC₅₀: 0.01 mg/mL). A significant positive correlation was observed between its antioxidant and hypoglycemic activities. Network pharmacology identified 11 core targets involved in oxidative stress and glucose metabolism, with functional enrichment pointing to the PPAR and steroid hormone signaling pathways. Molecular docking confirmed stable binding affinities of bornyl acetate, (-)-spathulenol, and (-)-pogostol to JAK2, NCOA2, and PPARA via hydrogen bonding and hydrophobic interactions. These findings provide a mechanistic basis for the dual antioxidant-hypoglycemic effects of AVEO and support its potential application in the development of functional foods and natural therapeutics targeting metabolic disorders.