Protective effects of 4‐geranyloxy‐2,6‐dihydroxybenzophenonel on DSS‐induced ulcerative colitis in mice via regulation of cAMP/PKA/CREB and NF‐κB signaling pathways

Abstract Hypericum sampsonii Hance has traditionally been used to treat enteritis and diarrhea. As one of the main benzophenones isolated from H. sampsonii , 4‐geranyloxy‐2,6‐dihydroxybenzophenonel (4‐GDB) has been shown to possess anti‐inflammatory effects. However, the therapeutic effect and potential mechanisms of 4‐GDB in ulcerative colitis (UC) remain unclear. This study aimed to evaluate the role of 4‐GDB in UC using a dextran sulfate sodium‐induced colitis mouse model. Intragastric administration of 4‐GDB (20 mg/kg/day) for 8 days significantly attenuated colonic injury, reduced the expression of inflammatory mediators, and improved colonic barrier function in mice with colitis. Furthermore, in vivo and in vitro experiments indicated that 4‐GDB could activate cAMP/PKA/CREB and inhibit the NF‐κB pathway. Collectively, 4‐GDB may be a potential agent for treating UC by regulating the cAMP/PKA/CREB and NF‐κB pathways.