Differences and Mechanisms of Combined Use of "Raw and Fried Ziziphi Spinosae Semen" in Anmeidan and Its Disassembled Prescriptions in Improving Anxiety and Cognitive Impairment in Insomnia Rat Model Based on Serum Metabolomics
10.13422/j.cnki.syfjx.20242336
- VernacularTitle:基于血清代谢组学探讨安寐丹“生熟酸枣仁”同用及拆方改善失眠大鼠焦虑与认知障碍的差异及机制
- Author:
Kang SUN
1
;
Bo XU
1
;
Zijing YE
1
;
Miao ZHU
1
Author Information
1. Ministry of Education Engineering Research Centre of Chinese Medicine Protection Technology and New Product Development for Elderly Brain Health， Hubei University of Chinese Medicine， Wuhan 430065， China
- Publication Type:Journal Article
- Keywords:
Anmeidan;
combined use of "raw and fried Ziziphi Spinosae Semen";
insomnia;
anxiety;
cognitive impairment;
metabolomics
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(10):36-43
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the differences in efficacy and endogenous metabolic mechanisms of Anmeidan with combined use of raw and fried Ziziphi Spinosae Semen and its disassembled prescriptions in treating anxiety and cognitive impairment in insomnia rats. MethodsSixty rats were randomly divided into six groups （n=10 per group）： blank group， model group， suvorexant group （30 mg·kg-1）， Anmeidan group （9.09 g·kg-1）， Anmeidan with absence of raw Ziziphi Spinosae Semen group （7.38 g·kg-1）， and Anmeidan with absence of fried Ziziphi Spinosae Semen group （7.38 g·kg-1）. An insomnia model was constructed by intraperitoneal injection of para-chlorophenylalanine （PCPA）， followed by gavage administration of Anmeidan or its disassembled prescriptions. Anxiety levels were assessed using the open field test， while cognitive ability was evaluated via the novel object recognition test. The pathological morphology of hippocampal neurons was examined using electron microscopy. Serum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for principal component analysis， metabolic profiling， identification of differential metabolites， and metabolic pathway analysis. ResultsCompared with the blank group， the model group exhibited significantly increased exercise mileage， exercise time， and the ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones exhibited a marked increase （P<0.05， P<0.01）， while the novel object recognition index significantly decreased （P<0.05）. Compared with the model group， the Anmeidan and suvorexant groups showed significantly reduced exercise mileage and exercise time （P<0.01）. The ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones decreased （P<0.05）， and a significant increase in the novel object recognition index （P<0.01）. However， the disassembled prescription groups showed no significant improvement in open field test and novel object recognition test indices. Electron microscopy revealed that the Anmeidan group improved the pathological morphology of hippocampal neurons in insomnia rats. Metabolomics analysis identified 10 potential differential metabolites associated with Anmeidan's therapeutic effects， involving metabolic pathways related to phenylalanine and tryptophan biosynthesis and metabolism， as well as the serotonergic pathway. ConclusionThe combined use of raw and fried Ziziphi Spinosae Semen in Anmeidan is more effective than its disassembled prescriptions in alleviating anxiety and cognitive impairment in PCPA-induced insomnia rats. The underlying mechanism may be associated with metabolic pathways related to phenylalanine， tryptophan， and serotonin.
