Oxymatrine improves L-arginine-induced acute pancreatitis related intestinal injury via regulating AKT/NFkB and claudins signaling

Oxymatrine (OMT) plays a significant role in chemical agents induced intestinal injury. However, its functional role in L-arginine (Arg) induced acute pancreatitis (AP) following intestinal injury and the corresponding molecular mechanism are unclear to our knowledge. We investigate OMT function in Arg induced AP following intestinal injury in vivo and vitro. OMT (4 mg/ml) decreased Arg (from 100 to 600 µM) induced IEC-6 cells growth in dose-dependent manner and inhibited Arg induced the increase of pAKT, bcl2, and the decrease of Bax. Meanwhile, OMT inhibited Arg (600 µM) induced the increase of pro-inflammatory cytokines TNF-a, IL-6, IL-1β, and NFkBp65 and the decrease of anti-inflammatory cytokine IL-10 expression. Moreover, the change of tight junction proteins claudins 1–4 expression induced by Arg was also reversed by OMT. Consistent with the results in vitro, OMT (50 mg/kg) inhibited Arg (250 mg/100 g) induced AP following intestinal injury in vivo. In detail, OMT resisted Arg induced inflammatory histology of both pancreas and intestine and inhibited Arg induced the change of pAKT, Bax, bcl2, TNF-a, IL-6, IL-1β, IL-10, NFkBp65, claudin 1–4 expression. Moreover, OMT inhibited Arg induced NFkBp65 and ICAM-1 expression in vivo by IHC. Oxymatrine improves Arg-induced acute pancreatitis following intestinal injury via inhibiting AKT/NFkB and claudins signaling.