Puerarin also reduced LPS, AST and ALP levels, improved damaged colon and liver tissues, inhibited neuroinflammatory damage mediated by the TLR4/MYD88/NF-κB signaling pathway, and up-regulated the levels of 5-HT and BDNF in the prefrontal cortex of the mice, thereby reversing CRS-induced depressive-like behaviors in depressed mice.<h4>Conclusion</h4>Puerarin can improve CRS-induced depression in mice by regulating the gut-liver-brain axis and its related molecules. Here, NFKB1 is linked to major depressive disorder.