<i>Semen Trigonellae</i> alleviates LPS‐induced depressive behavior via enhancing the abundance of <i>Ligilactobacillus</i> spp.

Abstract

Abstract 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.