Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions

摘要

Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric glial cells(EGCs),with decreased glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.