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Integration of chemical fingerprinting and multi-pathway pharmacological validation to evaluate the sleep-promoting efficacy of Ziziphus jujuba leaves from diverse origins

Wang R, Wang F, Li K, Wang X, Yu W, Sang Y

Journal of the science of food and agriculture, 2026

Abstract

Background: Ziziphus jujuba leaves (ZJL) are promising functional food ingredients for sleep support, yet their chemical composition and efficacy vary greatly with geographical origin, hindering quality standardization. This study aimed to systematically evaluate the sleep-promoting potential of ZJL from seven Chinese regions by integrating chemical fingerprinting and multi-pathway pharmacological validation.

Results: Chemical profiling of ZJL from seven regions revealed distinct compositional patterns: Neiqiu County (XN) exhibited the highest flavonoids (64.98 mg g-1) and polyphenols (78.23 mg g-1), Lin County (LL) was enriched in triterpenoid saponins, and Jia County (YJ) accumulated alkaloids. Entropy-weighted scoring of nine sleep-related bioactives ranked XN as the top origin, followed by LL and YJ. In para-chlorophenylalanine (PCPA)-induced insomniac mice, oral administration of ZJL extracts (from XN, LL, and YJ) significantly improved sleep latency and duration. XN-ZJL produced the strongest effects, restoring neurotransmitter balance (elevated γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT), reduced glutamate (Glu) and dopamine (DA)) and normalizing the Glu/GABA ratio. It also suppressed systemic inflammation (lowered tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)), mitigated oxidative stress (increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased malondialdehyde (MDA)), and protected neural structures in the…

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