灵芝乙醇提取物可缓解抑郁样行为，并与调节NF-κB/NLRP3相关神经炎症及BDNF/TrkB信号通路有关。

Abstract

Depression is frequently accompanied by immune-inflammatory activation, oxidative stress, and impaired synaptic plasticity. Although antidepressant-like effects of Ganoderma lucidum preparations, including ethanol extracts, have been reported, whether they are accompanied by coordinated changes in microglial NF-κB/NLRP3-related inflammation and BDNF/TrkB-associated synaptic plasticity remains unclear. This study examined behavioral and molecular changes associated with Ganoderma lucidum ethanol extract (GLEE) using chronic unpredictable mild stress (CUMS)- and lipopolysaccharide (LPS)-induced mouse models, together with BV-2 and PC-12 cell assays. In both mouse models, GLEE improved depressive-like behavioral indices. These changes were accompanied by lower peripheral and hippocampal pro-inflammatory cytokines, reduced hippocampal microglial activation, lower DHE fluorescence, and attenuated NF-κB/NLRP3-related protein alterations, together with enhanced BDNF/TrkB/CREB signaling, postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expression, and dendritic spine indices. In BV-2 cells, treatment with GLEE-containing serum was associated with lower inflammatory responses under LPS or LPS/Nigericin stimulation. Conditioned medium from GLEE-containing serum-treated BV-2 cells was also associated with preservation of BDNF, p-TrkB/TrkB, PSD95, and synaptophysin in PC-12 cells. JSH-23 and MCC950 response patterns were consistent with involvement of NF-κB- and NLRP3-related processes, respectively, but did not establish direct target engagement or a complete causal pathway. Collectively, GLEE exhibited antidepressant-like bioactivity as an edible-fungus-derived candidate functional ingredient, supporting further evaluation.