Protective effects of jujube seed extract against oxidative stress in HT22 cells and its sleep-promoting action through GABAergic receptors

Seok Hyun Chung ^a,b, Hyeongyeong Kim ^a,b, Singeun Kim ^c, Pan-Young Jeong ^c, Hyowon Lee ^a,b,*

^a Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, the Republic of Korea

^b Transdisciplinary Major in Learning Health Systems, Department of Healthcare Sciences, Graduate School, Korea University, Seoul 02841, the Republic of Korea

^c Life Science Research Institute, NOVAREX Co., Ltd., Cheongju 28220, the Republic of Korea

Jujube seed extract (JSE), rich in polyphenols and flavonoids, exhibits neuroprotective and sleep-enhancing properties. In vitro, JSE protected HT22 cells against oxidative stress by activating the Nrf2/HO-1 pathway and upregulating antioxidant enzymes. In vivo, JSE increased non-REM sleep and delta wave activity in pentobarbital- and caffeine-induced sleep models. Spinosin contributed to these effects. Long-term JSE administration upregulated GABAA, GABAB, and 5-HT1A receptors in brain tissue. These findings suggest that JSE offers dual benefits in mitigating oxidative stress and promoting sleep through antioxidant defense and neurotransmitter modulation, supporting its potential as a natural therapeutic agent.