The study investigated puerarin, a flavonoid from Pueraria lobata, for its antidepressant effects through the gut–liver–brain axis. Puerarin improved depression-related behavioral changes while helping restore gut microbiota balance, particularly by increasing beneficial Lactobacillaceae and Lactobacillus and reducing potentially harmful bacterial groups. It also improved intestinal and liver health and reduced LPS, AST, and ALP, indicating better gut and hepatic homeostasis. In the brain, puerarin increased 5-HT and BDNF and reduced inflammatory signaling through the TLR4/MYD88/NF-κB pathway, linking improved gut and liver function with reduced neuroinflammation. Overall, puerarin may support mental health by regulating gut microbiota, liver function, neurotransmitters, and neuroinflammation, highlighting its potential as a natural bioactive.
