Gastrodia elata polysaccharide alleviates depression via gut microbiota modulation and Keap1-Nrf2/BDNF-TrkB pathway activation

Oxidative stress plays a key role in the onset and development of depression, involving dysregulation of intestinal flora and abnormal cell signaling pathways. Gastrodia elata polysaccharide (GEP) presents great potential in neuroprotection and antidepressant effects. However, the specific mechanism underlying its neuroprotective effect remains unclear. This study elucidates how GEP alleviates depression in mice induced by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). This study investigated the effects of GEP on intestinal flora composition and cell signaling pathways. Additionally, the study investigated its effects in an vitro LPS-induced PC12 cell model. Results indicated that GEP pretreatment effectively mitigated CUMS- and LPS-induced depressive behavior in mice. 16S rRNA sequencing results showed that GEP significantly altered gut microbiota composition in the CUMS model, reduced the Firmicutes/Bacteroidota ratio and increased microbial diversity. Western blotting and qRT-PCR revealed the role of GEP in regulating the Keap1-Nrf2/BDNF-TrkB signaling pathway in vivo and in vitro. Our findings provide insights into the potential mechanisms underlying the neuroprotective effects of GEP while establishing a solid foundation for future utilization of GEP.