Chrysanthemum morifolium extract protects HT22 cells from oxidative stress and enhances sleep via GABAergic modulation: contribution of luteolin‐7‐glucoside

BACKGROUND Chrysanthemum morifolium has long been utilized in traditional medicine for its antioxidant and sedative properties, yet its potential in sleep regulation and neuroprotection against oxidative stress remains underexplored. This study investigates the antioxidant and sleep‐enhancing effects of C. morifolium extract (CE) in HT22 hippocampal neuronal cells and animal models, focusing on its bioactive component, luteolin‐7‐glucoside (L‐7‐G) and the underlying molecular mechanisms. RESULTS CE exhibited potent antioxidant activity, significantly reducing reactive oxygen species and malondialdehyde levels while improving cell survival under oxidative stress. It upregulated antioxidant enzyme expression and activated the Nrf2/HO‐1 pathway, effects linked to L‐7‐G. In pentobarbital‐induced sleep models, CE increased sleep duration by up to 1.41‐fold compared to controls, with L‐7‐G showing similar efficacy. Electroencephalography revealed enhanced δ‐wave activity and prolonged non‐rapid eye movement (NREM) sleep with CE treatment. In a caffeine‐induced insomnia model, CE reduced wake time, restored NREM sleep, and counteracted sleep disturbances by enhancing δ‐wave activity. Mechanistic analysis showed CE upregulated GABA A and 5‐HT 1A receptor expression, with its sleep‐promoting effects partially mediated through GABA A receptor interactions. CONCLUSION CE, particularly through L‐7‐G, exhibits significant potential as a natural agent for reducing oxidative stress and enhancing sleep quality, offering a promising avenue for managing sleep disorders.