基于皮质代谢组学探讨柴胡-白芍药对慢性不可预测性温和应激大鼠的抗抑郁作用
Antidepressant effect of Radix bupleuri - Radix paeoniae alba herb pair on chronic unpredictable mild stress rats based on cortical metabolomics.
作者信息
Cai Kanglin, Chen Xinyu, Cao Yongkai, Ran Liangdi, Bu Qinpeng, Hu Dajun, Feng Zhitao, Cao Meiqun
机构信息
The Second People's Hospital Affiliated to Three Gorges University, Yichang Second People's Hospital, Yichang, Hubei, 443000, China.
College of Medicine and Health Science of China Three Gorges University, Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Three Gorges University, Yichang, Hubei, 443002, China.
出版信息
BMC Complement Med Ther. 2025 May 10;25(1):168. doi: 10.1186/s12906-025-04898-8.
OBJECTIVE
Depression is a serious mental disorder, and its incidence rate has increased rapidly. Radix Bupleuri (root of Bupleurum chinensis DC. BR)-Radix Paeoniae Alba (root of Paeonia lactiflora Pall. PRA) herb pair has been historically used for treating depression in Traditional Chinese Medicine (TCM) while the mechanisms need to be fully revealed.
METHODS
The effects of the BR-PRA herb pair were investigated using a rat model of chronic unpredictable mild stress (CUMS). First, the depressive-like behavior of rats was evaluated by open field test (OFT), elevated plus-maze test (EMP), and forced swimming test (FST). Secondly, histomorphological changes in the CA1 and CA3 regions of the hippocampus were analyzed by hematoxylin-eosin, nissl, and Golgi staining. Ultra high-performance liquid chromatograph tandem quadrupole mass spectrometry (UHPLC-QTRAP-MS/MS) was performed to reveal potential antidepressant mechanisms.
RESULTS
Following CUMS exposure, rats displayed depressive-like behavior, and neuronal death in the hippocampal region was observed. Consequently, these abnormal changes were reversed by BR-PRA herb-pair intervention. A total of 26 different metabolites related to depression were identified by metabolomics, mainly involving eleven metabolic pathways of pentose phosphate pathway, purine metabolism, and amino sugar and nucleotide sugar metabolism. BR-PRA herb-pair improved four metabolites, including homocitrulline, N-acetyllysine, corticosterone, and N-acetylglutamate. It also may affect the development of depression by interfering with the hypothalamus-pituitary-adrenal axis (HPA axis), amino acid metabolism related to lysine and glutamate, and modulation of oxidative stress.
CONCLUSION
BR-PRA herb-pair alleviated depressive-like behavior in CUMS rats, recovered hippocampus damage, and regulated cerebral cortex metabolism, which may be related to the HPA axis, amino acid metabolism related to lysine and glutamate, and modulation of oxidative stress.
CLINICAL TRIAL NUMBER
Not applicable.
目的
抑郁症是一种严重的精神障碍，其发病率迅速上升。柴胡-白芍药对在传统中医中一直用于治疗抑郁症，但其作用机制尚需充分揭示。
方法
采用慢性不可预测轻度应激（CUMS）大鼠模型研究柴胡-白芍药对的作用。首先，通过旷场试验（OFT）、高架十字迷宫试验（EMP）和强迫游泳试验（FST）评估大鼠的抑郁样行为。其次，通过苏木精-伊红染色、尼氏染色和高尔基染色分析海马CA1和CA3区的组织形态学变化。采用超高效液相色谱串联四极杆质谱（UHPLC-QTRAP-MS/MS）揭示潜在的抗抑郁机制。
结果
CUMS暴露后，大鼠表现出抑郁样行为，并观察到海马区神经元死亡。因此，柴胡-白芍药对干预可逆转这些异常变化。代谢组学共鉴定出26种与抑郁症相关的不同代谢物，主要涉及磷酸戊糖途径、嘌呤代谢、氨基糖和核苷酸糖代谢等11条代谢途径。柴胡-白芍药对改善了4种代谢物，包括高瓜氨酸、N-乙酰赖氨酸、皮质酮和N-乙酰谷氨酸。它还可能通过干扰下丘脑-垂体-肾上腺轴（HPA轴）、与赖氨酸和谷氨酸相关的氨基酸代谢以及氧化应激调节来影响抑郁症的发展。
结论
柴胡-白芍药对减轻了CUMS大鼠的抑郁样行为，恢复了海马损伤，调节了大脑皮层代谢，这可能与HPA轴、与赖氨酸和谷氨酸相关的氨基酸代谢以及氧化应激调节有关。
临床试验编号
不适用。
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