Semen Trigonellae alleviates LPS-induced depressive behavior via enhancing the abundance of Ligilactobacillus spp.

The rising incidence rate of depression presents a substantial threat to human well-being. Semen Trigonellae (ST), the dried mature seeds of Trigonella foenum-graecum L., has a long-standing traditional reputation for alleviating anxiety and hopelessness. However, the anti-depressant mechanism of ST remains poorly understood. This study aimed to assess ST's anti-depressant, as well as explore its potential mechanism from a gut microbial aspect. The Kunming mice were challenged by lipopolysaccharide (LPS) to induce depression-like behavior and then orally administrated with aqueous extract of ST. The behavioral test, and hippocampal and serum biochemical indicators were detected to assess anti-depressant effect of ST. We utilized full-length 16S rRNA gene sequencing to investigate how ST influences gut microbiota modulation. Administration of ST mitigated LPS-induced depression-like behaviors. ST reversed the decrease in hippocampal 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels while reducing serum levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Microbial analysis revealed that administration of ST markedly shifted the gut microbiota structure, dramatically and dose-dependently increased the abundance of Ligilactobacillus murinus and Ligilactobacillus animalis. Experimentally, oral administration of live L. murinus and L. animalis to LPS-challenged mice yielded similar effects to ST in ameliorating depression, elevating 5-HT and BDNF, and reducing proinflammatory cytokines. These findings provide evidence that ST is a promising medical food for the management of depression, in which modulation of the gut microbiota, particularly enhancing the abundance of Ligilactobacillus plays an important role.