Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren Decoction.
10.19540/j.cnki.cjcmm.20211204.701
- Author:
Jia-Xing LIU
1
;
Jia-Han LI
1
;
Chen-Hui DU
2
;
Yan YAN
1
Author Information
1. Modern Research Center for Traditional Chinese Medicine, Shanxi University Taiyuan 030006, China Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University Taiyuan 030006, China Key Laboratory of Effective Substances Research and Utilization in Traditional Chinese Medicine of Shanxi Province Taiyuan 030006, China.
2. Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine Taiyuan 030619, China.
- Publication Type:Journal Article
- Keywords:
PCPA;
Suanzaoren Decoction;
UPLC-Q-TOF-MS/MS;
differential metabolites;
insomnia;
metabonomics
- MeSH:
Animals;
Chromatography, High Pressure Liquid/methods*;
Drugs, Chinese Herbal;
Hypothalamo-Hypophyseal System;
Metabolomics/methods*;
Pituitary-Adrenal System;
Rats;
Sleep Initiation and Maintenance Disorders/drug therapy*;
Tandem Mass Spectrometry
- From:
China Journal of Chinese Materia Medica
2022;47(6):1632-1641
- CountryChina
- Language:Chinese
-
Abstract:
Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1β and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.
