Valeriana jatamansi jones improves depressive behavior in CUMS mice by modulating vitamin B12-related ileal homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE

Valeriana jatamansi Jones (V. jatamansi) is a traditional Chinese medicine (TCM). It was recorded in Diannan Bencao, Compendium of Materia Medica and some local medical books and was described as useful in treating insomnia, distraction, poor mental health, vomiting and diarrhea.

AIM OF THE STUDY

To investigate whether the antidepressant effect of V. jatamansi may operate through modulating vitamin B12-related ileal homeostasis using a chronic unpredictable mild stress (CUMS) mouse model.

MATERIALS AND METHODS

A CUMS-induced depression model was established in mice for five weeks, after which V. jatamansi extracts were administered for three weeks. At week eight, the forced swimming test and novelty-suppressed feeding test were conducted. H&E staining assessed ileal pathology, while 16S rDNA sequencing analyzed changes in ileal microbiota. Additionally, B12 in serum, cubilin (CUBN) and amnionless (AMN) in ileal tissue, methionine synthase (MS) and homocysteine (Hcy) in the hippocampus were measured using ELISA, and the correlations between them and ileal microbiota were explored.

RESULTS

Mice in the model group exhibited significant depressive behavior. However, after treatment with V. jatamansi, immobility time and feeding latency were improved. H&E staining demonstrated the repairing effect of V. jatamansi on the ileum regarding tissue damage. The alpha and beta diversity of the ileal microbiota were regulated and converged to the normal group. Additionally, V. jatamansi modulated B12, CUBN, AMN, MS, and Hcy levels. Correlation analysis showed that there are certain correlations between a variety of microorganisms and B12-related factors.

CONCLUSION

These findings suggest that the mechanism of V. jatamansi in treating depression may be through repairing depression-associated intestinal damage. This repair process may affect the intestinal absorption and microbial production of B12. By reversing the reduction of serum B12, V. jatamansi ultimately reduces the infiltration of Hcy into the CNS.