Mass spectrum oriented metabolomics for evaluating the efficacy and discovering the metabolic mechanism of Naoling Pian for insomnia

Insomnia is an accompanying symptom of many diseases and is closely associated with neurodegenerative diseases. Naoling Pian (NLP) is a patented Chinese medicine mainly used to treat insomnia. To evaluate the sedative and hypnotic effects of NLP and its modulatory effects on biological metabolites and metabolic pathways, rats with p-chlorophenylalanine (PCPA)-induced insomnia were given different doses of NLP by oral gavage for seven days. Diazepam (DZP) served as a positive control. Behavior was measured using the open field test, and neurotransmitter levels in the brain tissue related to sleep were measured using ELISA. The metabolic profiles and biomarkers of PCPA-induced insomnia in rats before and after NLP administration were analyzed using UPLC-Q/TOF-MS combined with multivariate data analysis. The results showed that the levels of 5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, and dopamine in the brain tissue were significantly recovered in the NLP treatment groups, demonstrating similar or even superior therapeutic effects compared to the DZP group. The behavior of the PCPA-model rats partially recovered to normal levels after seven days of treatment. Metabolomics identified 30 metabolites in the urine as potential biomarkers of insomnia, and NLP significantly altered 25 of these, involving 21 metabolic pathways. NLP has a remarkable effect on insomnia, the therapeutic effects of which may be largely due to the rectification of metabolic disturbances. This is the first study of the sedative and hypnotic effects of NLP from a metabolomic perspective.