Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the Drosophila melanogaster model organism is hugely popular in sleep-related
drug screening studies. Seven-day-old virgin D. melanogaster was used to establish the
sleep deprivation model by repeated light stimulation at night. Using PySolo activity monitoring system and Drosophila activity as indices, the effective fractions of Zhi-Zi-Hou-Po decoction (
ZZHPD) for
insomnia were screened; the content of monoamine
neurotransmitters dopamine (DA), 5-hydroxyindole-3-acetic
acid (5-HIAA),
Homovanillic acid (HVA), and
5-hydroxytryptamine (5-HT) in the brain of D. melanogaster were determined by high-performance liquid chromatography-electro-chemical detection. The herb-compound-target-disease target network were further constructed through network pharmacology to identify the potential targets and pathways of
ZZHPD in the intervention of
insomnia. Finally, the molecular docking method was used for evaluating the binding characteristics of important compounds from
ZZHPD with related targets. The results showed that a certain dose of
ZZHPD and its
petroleum ether,
dichloromethane,
ethyl acetate, and
n-butanol fractions could improve sleep. The
dichloromethane fraction from
ZZHPD extracts showed the best anti-
insomnia effect among all extracts. It can also reduce the content of DA and HVA in the brain of D. melanogaster and increase
5-HT and
5-HIAA levels. The network pharmacology showed that the main active ingredients in
ZZHPD included
magnolol,
honokiol,
hesperidin, and so forth. According to the screening conditions, there were 71 targets and the result of KEGG enrichment analysis revealed that 73 pathways were associated with
insomnia, which were primarily involved in inflammatory response, central
neurotransmitter regulation, and apoptosis to relieve
insomnia. The molecular docking results clarified that
naringenin and
apigenin have an intimate relationship with GABAA
receptor, histamine H1,
orexin receptor type 2, and
interleukin-6. The mechanism of relieving
insomnia is the result of the interaction of multi-components, multi-targets, and multi-pathways, which provides a certain theoretical basis for the treatment of
insomnia and related diseases as well as clinical research.