[Dingzhi Pills alleviate LPS-induced depression-like behavior in mice by modulating metabolism and neuroplasticity]

Dingzhi Pills, a traditional Chinese medicine(TCM) formula, is frequently employed in clinical settings for treating depression, yet its treatment mechanism remains poorly understood. This study investigates the efficacy of Dingzhi Pills in mitigating depression and delineates the associated metabolic pathways. The chemical constituents of Dingzhi Pills were identified by ultra-fast liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UFLC-Q-TOF-MS/MS). The optimal dose for treating depression in mice was determined via a mouse model of behavioral despair. Furthermore, a lipopolysaccharide(LPS)-induced depression model was established in mice and used to validate the results of pharmacological and metabolomic analyses. The results indicated that Dingzhi Pills ameliorated depression-like behaviors in mice, attenuated the LPS-induced rises in levels of inflammatory cytokines, and suppressed the activities of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), thus reducing the glutamate level. Additionally, Dingzhi Pills enhanced the expression of brain-derived neurotrophic factor(BDNF), tyrosine receptor kinase B(TrkB), mammalian target of rapamycin(mTOR), and glutamate A1(GluA1). Metabolomic profiling of the brain tissue revealed 46 unique metabolites, which served as candidate biomarkers for the antidepressant effect of Dingzhi Pills. Collectively, the data demonstrate that Dingzhi Pills alleviates depression by modulating inflammatory responses, the AMPA/BDNF/TrkB/mTOR signaling pathway, the biosynthesis of valine, leucine, and isoleucine, and the metabolism of 2-oxycarboxylic acid, providing scientific evidence for the antidepressant effect of Dingzhi Pills.