Pure Total Flavonoids From Citrus Ameliorate NSAIDs-Induced Intestinal Mucosal Injury via Regulation of Exosomal LncRNA H19 Expression

Abstract

Non-steroid anti-inflammatory drugs (NSAIDs) are widely used in the clinic because of their excellent antipyretic, anti-inflammatory, and analgesic effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. How to balance the use and side effects of NSAIDs is an urgent clinical problem. Elucidating the mechanism related to disrupting the intestinal mucosal barrier caused by NSAIDs and achieving targeted drug prevention or treatment is the key. In the study, we investigated the mechanism of exosomal lncRNA H19 in the intestinal mucosal barrier injury associated with NSAIDs and the intervention of pure total flavonoids from Citrus (PTFC). Results showed that IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest protective autophagy levels and intestinal mucosal mechanical barrier function disturbance. By contrast, though the IEC-6 cells co-cultured with the exosomes extracted from rats receiving early prevention with PTFC still exhibited a certain inhibition of autophagy and disturbance of intestinal mucosal mechanical barrier function, both were significantly better. The prevention effect was proportional to the concentration of PTFC administered. Exosomal lncRNA H19 is the critical RNA in the above mechanism, which regulates protective autophagy and intestinal mucosal mechanical barrier function.