Speaker
Description
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with complex pathogenesis. Globally, the number of UC cases has reached 5 million, posing a significant threat to public health and imposing a substantial economic burden worldwide. There is currently a lack of highly effective and accessible clinical medications. Our previous studies have demonstrated that oxidized berberine (OBB) shows promising potential in the intervention and treatment of UC. Single-cell analyses revealed that OBB significantly upregulates the expression of kallikrein Klk1 in fibroblasts and modulates the bradykinin receptor B1R, thereby regulating the inflammatory polarization of macrophages and exerting therapeutic effects. Metagonomics and targeted metabolomics showed that OBB exerted anti-inflammatory effects by regulating the metabolism of prostaglandin E2(PGE2), an arachidonic acid-derived metabolite associated with Akkermansia muciniphila (AKK), in a synergistic manner. Accordingly, we supposed that OBB targeted the Klk1-B1R axis to simultaneously repair the intestinal epithelial barrier and modulated immune responses. We employed cutting-edge interdisciplinary approaches to dissect the pharmacological mechanism of OBB regulating the Klk1-B1R axis; and elucidated the molecular basis of OBB targeting Klk1-B1R axis to modulate macrophage inflammatory polarization; finally, uncovered the molecular mechanisms by which OBB regulates AKK-mediated arachidonic acid metabolism to exert anti-inflammatory effects. The study provided novel and effective therapeutic targets and candidate drug molecules for the treatment of UC.