Metabolomics Based on Peripheral Blood Mononuclear Cells to Dissect the Mechanisms of Chaigui Granules for Treating Depression

Dehua Huang; Liwen Wang; Yanfei Wu; Xuemei Qin; Guanhua Du; Yuzhi Zhou

doi:10.1021/acsomega.1c06046

Metabolomics Based on Peripheral Blood Mononuclear Cells to Dissect the Mechanisms of Chaigui Granules for Treating Depression

ACS Omega. 2022 Mar 7;7(10):8466-8482. doi: 10.1021/acsomega.1c06046. eCollection 2022 Mar 15.

Authors

Dehua Huang^{1

2}, Liwen Wang^{1

2}, Yanfei Wu³, Xuemei Qin^{1

2}, Guanhua Du^{1

2

4}, Yuzhi Zhou^{1

2}

Affiliations

¹ Modern Research Center for Traditional Chinese Medicine, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, 92 Wucheng Road, Xiaodian District, Taiyuan 030006, Shanxi, P. R. China.
² Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, 92 Wucheng Road, Xiaodian District, Taiyuan 030006, Shanxi, P. R. China.
³ Department of Traditional Chinese Medicine, First Hospital of Shanxi Medical University, Yingze District, Taiyuan 030001, Shanxi, China.
⁴ Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xicheng District, Beijing 100050, P. R. China.

Abstract

Chaigui granules were a traditional Chinese medicine (TCM) preparation with antidepressant effects derived from a famous antidepressant prescription. It was of great significance to clarify the antidepressant mechanism of Chaigui granules for the clinical application of this drug. In this study, a chronic unpredictable mild stress (CUMS) depression model was successfully established, and behavioral indicators were used to evaluate the antidepressant effect. Second, the CD4+, CD8+, and CD4+/CD8+ levels were detected in peripheral blood. Meanwhile, the amount of inflammatory cytokines was determined in serum. Correspondingly, LC/MS-based peripheral blood mononuclear cell (PBMC) metabolomics was used to investigate vital metabolic pathways participating in the antidepressive effects of Chaigui granules. Finally, bioinformatics technology was further employed to discover the potential antidepressant mechanism of Chaigui granules regulating the immune system. The results suggested that the administration of Chaigui granules significantly improved CUMS-induced depressive symptoms. Chaigui granules could improve immune function by regulating T lymphocyte subsets, increasing anti-inflammatory cytokine levels of IL-2 and IL-10, and reducing pro-inflammatory cytokine levels of TNF-α, IL-1β, and IL-6. In addition, metabolomics results of PBMCs showed that Chaigui granules improved 14 of the 25 potential biomarkers induced by CUMS. Metabolic pathway analyses indicated that purine metabolism was the critical metabolic pathway regulated by Chaigui granules. Furthermore, correlation analysis indicated that 13 key biomarkers were related to immune-related indicators. The metabolite-gene network of 13 key biomarkers was investigated by using bioinformatics. The investigation showed that 10 targets (5'-nucleotidase ecto; 5'-nucleotidase, cytosolic IB; 5'-nucleotidase, cytosolic II; etc.), mainly belong to the purine metabolism, might be potential targets for Chaigui granules to exert their antidepressant effects by improving immune function impairment. Together, our results suggested that Chaigui granules might exert antidepressant effects by improving immune function and regulating the purine metabolic pathway in PBMCs. This work used PBMCs metabolomics as an entry point to study the antidepressant mechanism of Chaigui granules, which provided a new way to elucidate the mechanism of a traditional Chinese medicine prescription.