Arctigenin, a natural ERβ ligand occurring in edible burdock, accelerates focal adhesion disassembly of colon epithelial cells via enhancing autophagic degradation of paxillin to facilitate mucosal healing in ulcerative colitis

Abstract

Burdock is consumed as a vegetable in the Asian region and is also used in medicinal dishes or health soups. Our previous studies demonstrated that arctigenin, a natural agonist of estrogen receptor β (ERβ) occurring in burdock, can promote colonic mucosal healing in the context of ulcerative colitis (UC). Whether and how arctigenin intervenes in focal adhesion disassembly, a critical step for migration and wound healing of colon epithelial cells, were examined within this research. The results showed that arctigenin substantially accelerated focal adhesion disassembly and therefore facilitated migration and wound healing of colonic epithelial cells. Mechanistically, arctigenin reduced excitatory amino acid transport to specifically enhance autophagic degradation of paxillin, thereby accelerating focal adhesion disassembly through an ERβ-dependent pathway. In colitis-induced mice, ERβ knockout significantly attenuated promotion of colonic mucosal healing by arctigenin. These findings indicate that arctigenin is a promising mucosal healing promoter, which functions by accelerating focal adhesion disassembly in an ERβ-dependent manner.