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 GABA
A
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.
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