WeiNaiAn capsule attenuates intestinal mucosal injury and regulates gut microbiome in indomethacin-induced rat

Indomethacin, as a non-steroidal anti-inflammatory drugs, is widely used in the clinic. However, it can cause severe injury to the gastrointestinal tract and the incidence is increasing. It has become an essential clinical problem in preventing intestinal damage. Teprenone has been reported to have a significant positive effect on intestinal mucosal lesions, but long-term use of teprenone can elicit adverse reactions. WeiNaiAn capsule is a traditional Chinese medicine formulation used widely in the treatment of gastric and duodenal mucosal injury. However, how WNA protects against intestinal mucosal injury and its mechanism of action are not known. In this study, WeiNaiAn capsule or Teprenone treatment improved the intestinal mucosal pathological score and antioxidant level in indomethacin-induced rats. 16S rRNA sequence data showed WeiNaiAn capsule reverted the structure community and replenished the beneficial bacteria. Furthermore, fingerprint analysis revealed multiple components of WeiNaiAn capsule, including calycosin glucoside, ginsenoside Rg1, ginsenoside Rb1, taurocholic acid sodium, formonetin, and calycosin glucoside. The components of WeiNaiAn capsule promoted the wound healing of the epithelial cell in vitro. Moreover, the components of WeiNaiAn capsule inhibited the protein expressions of phosphoinositide 3-kinase /protein kinase B /mammalian target of rapamycin in hydrogen peroxide or lipopolysaccharides-induced cell model. In conclusion, WeiNaiAn capsule improves intestinal mucosal injury by regulating cell migration, enhancing antioxidant activity, and promoting the structure of the bacterial community homeostasis, the multiple targets provide the parameters for the treatment in the clinic.