With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in
insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce
insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and
neurotransmitters in the hippocampus of
insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential
biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and
gamma aminobutyric acid(
GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of
glucose(Glu)(except low-dose CNG). Among them,
estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential
biomarkers related to
insomnia. MetPA analysis showed 4 metabolic pathways of
estazolam in intervening
insomnia and 3 metabolic pathways of high-dose CNG in intervening
insomnia, involving
purine metabolism,
glycerophospholipid metabolism,
histidine metabolism, and
caffeine metabolism. CNG can alleviate
insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.