Ziziphi Spinosae semen extract ameliorates insomnia by regulating hypothalamic GABA/Glu balance and gut microbiota Lactobacillus johnsonii

Ziziphi Spinosae Semen (ZSS) is a notable seed food recognized for its sedative and sleep-promoting effects. ZZS improved sleep status and cognitive ability, and attenuated neuronal damage in the PCPA-induced insomnia rats. ZSS improved hypothalamic GABA/Glu balance by elevating GABA levels and GABA/Glu ratio, while lowering Glu levels. ZSS significantly increased expression of GAD67, GABRA1, and GABRG2, and decreased expression of GluR1, NMDAR1, and mGluR5. Notably, L. johnsonii emerged as one of the most significantly enriched microbial species following ZSS treatment, and administration of L. johnsonii showed effects similar to ZSS in improving GABA/Glu balance. Finally, anti-insomnia effects of ZSS were transferable to recipients through fecal microbiota transplantation, while ZSS treatment failed to ameliorate insomnia with depleted gut microbiota. This research validated the anti-insomnia effects of ZSS, along with its regulatory effects on GABA/Glu balance and gut microbiota, offering potential benefits for its utilization in the functional food sector. • ZSS regulated GABA/Glu balance. • ZSS modulated gut microbiota, notably increasing L. johnsonii . • L. johnsonii promoted GABA/Glu balance, exhibiting similar effects of ZSS. • FMT and gut microbiota depletion confirmed the importance of gut microbiota in ZSS treatment of insomnia.