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

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.

Exploring the molecular mechanism of Nux Vomica in treating ischemic stroke using network pharmacology and molecular docking methods

“…[ 45 ] PTGS2 encodes COX-2, a rate-limiting enzyme for the arachidonic acid metabolism of prostaglandins, its expression increases in response to cerebral ischemia, which promotes inflammatory responses and exacerbates neurological damage in the brain. [ 46 ] Stigmasterol can down-regulate PTGS2 expression by inhibiting the NF-κB pathway, which can promote cell proliferation, migration, and angiogenesis, and reduce inflammation and cell apoptosis, thereby decreasing neural damage after cerebral ischemia. [ 47 ]…”

“…[45] PTGS2 encodes COX-2, a rate-limiting enzyme for the arachidonic acid metabolism of prostaglandins, its expression increases in response to cerebral ischemia, which promotes inflammatory responses and exacerbates neurological damage in the brain. [46] Stigmasterol can down-regulate PTGS2 expression by inhibiting the NF-κB pathway, which can promote cell proliferation, migration, and angiogenesis, and reduce inflammation and cell apoptosis, thereby decreasing neural damage after cerebral ischemia. [47] GO enrichment analysis revealed that NV is mainly involved in BP such as the acetylcholine receptor signaling pathway, cellular response to acetylcholine, postsynaptic signal transduction, serotonin receptor signaling pathway, and neurotransmitter receptor activity.…”

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

“…L-isoleucine, sebacic acid, and allantoin were identified as potential pharmacodynamic biomarkers related to the efficacy of this TCM. Similarly, LC-MS-based metabolomics of peripheral blood mononuclear cells (PBMCs) was used to investigate the antidepressant mechanism of Chaigui granules [115]. Their antidepressant effects were attributed to improved immune function and regulation of the purine metabolic pathway in PBMCs.…”