Psychedelics have emerged as a promising novel therapeutic approach for major depressive disorder (MDD). Altered activity and structural atrophy of the prefrontal cortex, hippocampus, and limbic struc Show more
Psychedelics have emerged as a promising novel therapeutic approach for major depressive disorder (MDD). Altered activity and structural atrophy of the prefrontal cortex, hippocampus, and limbic structures are associated with depressive disorders. Psilocybin may reverse the loss of synaptic connections and restore the function of these brain regions. In this study, we investigated the effects of psilocybin on rat behavior, hippocampal neurogenesis, expression level of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis activity. Psilocybin administered in two doses (0.6 mg/kg, s.c., 7 days apart) reversed anhedonia in stressed rats, produced antidepressant-like effects in the forced swim test (FST), and exerted anxiolytic activity in the light/dark box (LDB), elevated plus maze (EPM), and open field (OF) tests in stressed animals. Psilocybin induced hippocampal neurogenesis as evidenced by increasing the number of BrdU-positive cells (an exogenous marker of cell proliferation and survival), DCX-positive cells (a marker of immature neurons), and Ki-67-positive cells (an endogenous marker of cell proliferation) in stressed animals. Stress-induced reductions in BDNF expression levels appeared to be associated with normalization of HPA axis activity. These findings underscore the role of psilocybin-induced neuroplasticity in the antidepressant and anxiolytic mechanisms of psychedelics. Show less
Hao-Lin Chu, Nan Sun, Qin Tang+3 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
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 inves Show more
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. Show less