Akebia trifoliata pericarp extract ameliorate inflammation through NF-κB /MAPKs signaling pathways and modify gut microbiota

Akebia trifoliata fruit, a popular edible berry in Asian, are widely consumed as daily fruits or functional foods. Our previous study found several bioactives from Akebia trifoliata pericarp extract (APE), and preliminary investigated their anti-inflammatory activity. However, the underlying mechanism of APE behind the observed anti-inflammatory effects are still unknown. Thus, the bioactive profiles and anti-inflammatory mechanism of APE were investigated by a combination of chemical assays, UPLC-LTQ-Orbitrap-MS technique, LPS-induced RAW264.7 cells and DSS-induced mice model. The results showed that the phenolic acids and terpenoids were major bioactives of APE, which could inhibit the production of NO and PGE2 by blocking the expression of iNOS and COX-2 in RAW264.7 cells as well as reduce the expression of TNF-, IL-6, IL-1, and suppress the phosphorylation of p-65, IκB and MAPKs (p38, ERKs, JNKs) proteins both in vitro and in vivo. Furthermore, APE treatment could regulate gut microbiota by increasing the richness of Rikenellaceae, Lactobacillaceae and reducing that of Lachnospiraceae and Ruminococcaceae. Summarily, these findings clearly demonstrated that APE mitigated inflammation by restraining the production of cytokines through NF-κB and MAPKs signal pathways, and altering gut microbiota, which could be a potential functional food for the treatment and prevention of inflammatory bowel disease.