Exploring the potential antidepressant mechanisms of puerarin: Anti-inflammatory response via the gut-brain axis

Puerarin has been shown to have a good antidepressant effect, and our previous study found that it can remedy stress-induced dysbiosis. However, its gut microbiota-related mechanism has not been fully elucidated. Therefore, this study aimed to investigate the potential link between puerarin on gut microbiota and inflammatory responses in depressed rats.A chronic unpredictable mild stress (CUMS) rat model of depression was established, open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST) were used to evaluate its antidepressant effect. 16S rRNA sequencing was performed to identify the rat fecal microflora. At the same time, inflammatory cytokines, colonic histopathological changes, and brain-derived neurotrophic factor (BDNF), nuclear factor kappa-B (NF-κB), inhibitor a of NF-κB (IκB-α) protein expression were detected.Puerarin attenuated CUMS-induced depressive-like behavior and gut microbiota dysregulation in rats, significantly reducing the abundance of harmful bacteria such as Desulfovibrio, Verrucomicrobiae, and Verrucomicrobia. In addition, puerarin can also reduce the pro-inflammatory factors and increase the level of anti-inflammatory factors in depressed rats, improve the damaged colon tissue, enhance the expression of BDNF and IκB-α in the hippocampus and inhibit the expression of NF-κB.Direct evidence that puerarin improves depressive-like behaviors via gut microbiota is lacking.The underlying mechanism of puerarin's antidepressant-like effect is closely related to the bidirectional communication of the microbiota-gut-brain axis by regulating the inflammatory response.