The Extract from the Stem and Leaf of Paeonia lactiflora Pall Has Demonstrated an Anti-Oxidative Stress Effect in Alleviating Diarrhea by Regulating the Gut-Liver Axis

This study investigated the preventive effects and mechanisms of <i>Paeonia lactiflora</i> pall stem and leaf extract (PLE) on oxidative stress-induced diarrhea in broilers, using a Diquat (DQ)-induced model. Results indicated that PLE significantly improved growth performance, increased average daily gain (ADG), reduced feed-to-gain ratio (F/G), and enhanced liver and kidney indices. PLE alleviated DQ-induced oxidative stress diarrhea by reducing the diarrhea rate by 63.84%, upregulating mRNA expression of <i>MUC2</i>, <i>Claudin-1</i>, <i>ZO-1</i>, and <i>Occludin</i>, and decreasing AST and ALT activities in serum. Additionally, PLE increased levels of CAT, SOD, GSH-Px, and GSH while reducing PCO and MDA levels in serum, intestine, and liver tissues. Furthermore, PLE increased acetic acid content and decreased propionic acid, butyric acid, and isobutyric acid contents. PLE also altered gut microbiota by up-regulated Bacteroidetes and <i>Barnesiella</i> and down-regulated Firmicutes and <i>unclassified_o__Eubacteriales</i>. Network pharmacology suggested that PLE acts via the PI3K-Akt-Nrf2 pathway, confirmed by up-regulated mRNA expression of PI3K, AKT, Nrf2, NQO1, and HO-1, and down-regulated Keap1 in intestinal and liver tissues. Correlation analysis revealed significant associations between <i>Barnesiella</i> and <i>unclassified_o__Eubacteriales</i> with short-chain fatty acids and PI3K-Akt-Nrf2 pathway-related genes. Thus, PLE prevents and alleviates oxidative stress-induced diarrhea in broilers by modulating the PI3K-Akt-Nrf2 pathway, regulating gut microbiota, and influencing short-chain fatty acids.