Antidepressant effect of Radix bupleuri - Radix paeoniae alba herb pair on chronic unpredictable mild stress rats based on cortical metabolomics.

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.