Fufang Gaoziban Pian alleviates anxiety and depression-like behavior in mice via the gut-brain axis: Involvement of the estrogen signaling pathway

Background/Objective

Fufang Gaoziban Pian (FGZBP) is a Uyghur patent Chinese medicine, and it has been shown to improve depressive symptoms. However, its impact on co-morbidity of anxiety and depression, as well as its exploration of the potential mechanisms, have not been probed in sufficient depth. This research explored the impacts of FGZBP on anxiety and depression-like behaviors, along with its underlying mechanisms in mice exposed to a stress model.

Research design/Methodology

In this study, mice with chronic unpredictable mild stress were treated with different doses of FGZBP. The ultrastructure of hippocampal synapses was assessed via transmission electron microscopy, and physiological changes in brain and intestinal tissues were evaluated using staining. Simultaneously, the modulatory effects of the FGZBP on brain and colonic transcriptions were assessed by RNA sequencing of brain and colon tissues, and potential mechanisms were explored. Additionally, inflammatory markers and candidate metabolites in serum and brain tissue were analyzed using RT-qPCR and ELISA, using 16 s rRNA sequence to test changes of intestinal microbiome.

Results

The results demonstrated that the high-dose FGZBP effectively alleviated depressive and anxious behaviors. It ameliorated brain histological and intestinal damage, upregulated the expression of genes linked with the estrogen receptor pathway in CUMS mice. Thereby reversing microglial activation, diminishing the secretion of pro-inflammatory mediators, and raising the expressions of BDNF and PSD-95, which was achieved by the high-dose FGZBP. Simultaneously, the high-dose FGZBP dysregulated the intestinal microecological disturbances and alleviated colonic oxidative stress and physiological changes induced by CUMS.

Conclusion

In summary, our findings suggested that the FGZBP reversed inflammation and oxidative stress in CUMS mice by regulating estrogen signaling pathways via the gut-brain axis, thereby reducing depressive and anxious behaviors.