Cyclic helix B peptide alleviates liver fibrosis via attenuating ROS-mediated pyroptosis

Liver fibrosis, a reversible yet potentially progressive condition leading to cirrhosis, arises from chronic liver injury caused by factors such as viral hepatitis, alcohol, or fatty liver disease, necessitating effective treatments. Moreover, cyclic helix B peptide (CHBP) was designed to maintain erythropoietin (EPO) activity and protect tissue from the adverse effects of EPO. This study explored CHBP as a therapeutic candidate, focusing on its ability to mitigate oxidative stress and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome-mediated pyroptosis. In vitro experiments using AML12 cells and cocultured PHPCs and PHSCs demonstrated that CHBP reduced ROS levels, suppressed NLRP3 inflammasome activation, and decreased the levels of pyroptosis-related proteins, while CHBP also attenuated inflammation and lipid accumulation. In vivo, CHBP treatment improved liver histology, decreased serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels, and reduced collagen deposition in a mouse model of CCl₄-induced liver fibrosis. These findings indicate that CHBP alleviates liver fibrosis by targeting ROS-driven oxidative stress and the NLRP3 inflammasome pathway, highlighting its potential as a novel therapeutic agent for liver fibrosis.