Antidepressant Effects and Mechanisms of the Total Iridoids of Valeriana jatamansi on the Brain-Gut Axis.

Valeriana jatamansi is widely used in Chinese folk medicine and contains iridoids as important active ingredients. The brain-gut axis describes a complex bidirectional system between the central nervous system and the gastrointestinal tract. Herein, we evaluated the antidepressant effects of total iridoids of Valeriana jatamansi (TIV) and preliminarily investigated the effects of gut microbiota on their antidepressant effects using a chronic, unpredictable mild-stress mouse model. Mice were given 5.7, 11.4, or 22.9 mg/kg TIV for 1 week. Fluoxetine (2.6 mg/kg) served as a positive control. Body weight was measured, and behavioral tests including SPT and TST were applied. Colon pathology was assessed through hematoxylin-eosin staining. Additionally, levels of serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), substance P (SP) and corticotropin-releasing factor (CRF) in the hippocampus and colon were measured by ELISA. In addition, 16SrRNA gene sequencing was performed to explore changes in intestinal microbiota richness and diversity. Our results demonstrated that the model group showed significant depression-like behavior, while the fluoxetine group showed improved depression-like symptoms; after administration, TIV increased body weight, sucrose solution consumption, and ameliorated depression-like behaviors. The overall cell degeneration in colons also improved. In addition, TIV modulated the levels of 5-HT, NE, SP, and CRF expression in the hippocampus and colon. The diversity and richness of gut microbes increased compared to the model group. We therefore conclude that the antidepressant effects of TIV may be related to gut flora structures and regulation of 5-HT, NE, SP, and CRF in the brain and intestine.