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Hemerocallis citrina  Baroni (HC) is an edible plant in Asia, and it has been traditionally used for sleep-improvement. However, the bioactive components and mechanism of HC in sleep-improvement are still unclear. In this study, the sleep-improvement effect of HC hydroalcoholic extract was investigated based on a caffeine-induced insomnia model in  Drosophila melanogaster  ( D. melanogaster ), and the ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI-Orbitrap-MS) and network pharmacology strategy were further combined to screen systematically the active constituents and mechanism of HC in sleep-improvement. The results suggested HC effectively regulated the number of nighttime activities and total sleep time of  D. melanogaster  in a dose-dependent manner and positively regulated the sleep bouts and sleep duration of  D. melanogaster . The target screening suggested that quercetin, luteolin, kaempferol, caffeic acid, and nicotinic acid were the main bioactive components of HC in sleep-improvements. Moreover, the core targets (Akt1, Cat, Ple, and Sod) affected by HC were verified by the expression of the mRNA of  D. melanogaster . In summary, this study showed that HC could effectively regulate the sleep of  D. melanogaster  and further clarifies the multi-component and multi-target features of HC in sleep-improvement, which provides a new insight for the research and utilization of HC.

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Study on the Sleep-Improvement Effects of Hemerocallis citrina Baroni in Drosophila melanogaster and Targeted Screening to Identify Its Active Components and Mechanism