N-(3',4'-dimethoxycinnamonyl) anthranilic acid alleviates severe acute pancreatitis by inhibiting intestinal barrier...

Severe acute pancreatitis (SAP) can affect intestinal barrier with a high mortality. To date, effective therapies for SAP are still in urgently need. The purpose of this study was to investigate the role of anthranilic acid active synthetic derivative, N-(3',4'-dimethoxycinnamonyl) anthranilic acid (3,4-DAA), in intestinal barrier dysfunction of SAP. In this study, SAP mice model was induced by caerulein combined with lipopolysaccharide (LPS). SAP mice were pretreated with 3,4-DAA orally. Histological structures of pancreatic and intestinal tissues were observed via hematoxylin-eosin (H&E) staining. Pancreas myeloperoxidase (MPO), serum lipase, and amylase were detected using corresponding kits. Western blot analysis and reverse transcription and quantitative PCR (RT-qPCR) were employed to determine the levels of inflammatory factors in both pancreatic and intestinal tissues. Moreover, the levels of intestinal barrier-related proteins, NLRP3 inflammasome and NF-κB pathway were examined by western blot analysis. Result revealed that 3,4-DAA significantly attenuated pancreas and intestine damage, inhibited the release of inflammatory factors and intestinal barrier dysfunction. Moreover, the expression of NLRP3 and phospho-NF-κB p65 in pancreatic and intestinal tissues was notably suppressed by 3,4-DAA. To sum up, these results demonstrated that 3,4-DAA could ameliorate SAP, partly attributing to the inhibition of intestinal barrier dysfunction and the release of inflammatory factors. These findings may provide a new mechanism support for 3,4-DAA application in the clinical treatment of SAP.