KaiXinSan (KXS) improved motor activity and sleep status in insomniac rats.
KXS alleviated hippocampal neuronal damage in the rat model.
ELISA analysis indicated that KXS increased levels of serotonin and GABA while decreasing dopamine and norepinephrine levels.
KXS reduced inflammatory markers including TNF-α, IL-6, IL-1β, and reactive oxygen species.
and transcriptomics suggested that KXS may regulate serotonin synapse and TNF signaling pathways.
KXS reversed abnormal metabolism of arachidonic acid and tryptophan in insomniac rats.
Active components of KXS showed strong binding affinity to proteins that may upregulate 5-HTR1A and GABAA expression while inhibiting TNF-α and IL-6 expression.
Simplified
BACKGROUND: KaiXinSan (KXS) is a classic Chinese herbal compound used for treating and related mental disorders. Modern medical studies have shown that KXS can treat depression, Alzheimer's disease, memory loss, and other conditions. In addition, the effect of KXS in treating insomnia has been confirmed in clinical applications and animal experiments. However, the mechanism by which KXS treats insomnia remains unclear. The purpose of this study is to evaluate the impact of KXS on insomnia and explore its mechanism.
METHODS: A rat insomnia model was established using p-chlorophenylalanine (PCPA). Pharmacodynamic evaluation was performed via animal behavioral assessments, ELISA detection of biochemical indicators, and pathological tissue observation. The key mechanisms of KXS in treating insomnia were clarified through an integrated approach combining serum pharmacochemistry, , transcriptomics, and metabolomics. These mechanisms were further validated by molecular docking, in vivo, and in vitro experiments.
RESULTS: KXS improved motor activity and sleep status in insomniac rats and alleviated hippocampal neuronal damage. ELISA analysis showed that KXS increased levels of 5-HT and GABA while reducing DA and NE levels in rats. Additionally, KXS decreased levels of TNF-α, IL-6, IL-1β, and ROS. Using UPLC-Q-Orbitrap MS/MS technology, 169 chemical components and 39 blood- enterable components of KXS were identified. Results from network pharmacology and transcriptomics indicated that KXS treats insomnia by regulating serotonin synapse and TNF signaling pathways. Furthermore, KXS reversed abnormal arachidonic acid and tryptophan metabolism in insomniac rats. Molecular docking, immunohistochemistry, and Western blotting showed that active components of KXS exhibited strong binding affinity to relevant proteins, upregulating 5-HTR1A and GABAA protein expression while inhibiting TNF-α and IL-6 protein expression. Cell experiments confirmed that KXS medicated serum reduced LPS induced neuronal damage and inflammatory responses in neural cells.
CONCLUSIONS: KXS treats insomnia by regulating serotonin synapse signaling pathways and inflammatory responses, and influencing arachidonic acid and tryptophan metabolism.
Key numbers
5-HT levels increased
Increase in 5-HT Levels
KXS treatment improved 5-HT levels in insomniac rats.
TNF-α and IL-6 decreased
Decrease in Inflammatory Markers
KXS reduced TNF-α and IL-6 levels in serum.
Movement distance increased
Improvement in Motor Activity
KXS treatment led to greater movement distance compared to the control group.
Full Text
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Declarations. Ethics approval and consent to participate: This study was approved by the Animal Ethics Committee of Shaanxi University of Traditional Chinese Medicine for the humane care of animals (Clinical trial number: SUCMDL20240613001, SUCMDL20240902001). And it complied with all the regulations of animal experimentation ethics. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests.
PubMed
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