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

Introduction

The intestinal tract is the main site of digestion and absorption of nutrients (Assimakopoulos et al., 2018, Liang et al., 2023). Despite the protective barrier provided by the mucosa, ingested materials (such as inappropriate drugs) and microbial pathogens can induce oxidative injury and gastrointestinal inflammatory responses involving the epithelium and immune/inflammatory cells (Bhattacharyya et al., 2014). With the anti-inflammatory, analgesic, and antipyretic effects, non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, are widely used in the clinic. Strikingly, NSAIDs can cause intestinal damage and ulcers and the incidence is increasing (Scheiman, 2016). 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 because it increases the vascular endothelial growth factor (VEGF) content, reduces the damage caused by free radicals, and suppresses the expression of proteinase-activated receptor (PAR)1 and PAR2 (Wu et al., 2019, Chao et al., 2021). Thus, teprenone is often selected as a drug for the study of injury to and repair of the gastrointestinal mucosa. Nevertheless, long-term use of teprenone can elicit adverse reactions such as headache, rash, constipation, abdominal distension, diarrhoea, nausea, and abdominal pain.

Traditional Chinese medicine (TCM) formulations have been widely used in the management of gastrointestinal disease due to their definite efficacy and few side effects in the clinic. As a longstanding TCM formulation produced by Guangzhou Zhongyi Pharmaceutical Industry (Guangzhou, China) and used against gastric disease, WeiNaiAn (WNA) capsule (patent number: ZL200510037077.7) has been approved by the National Medical Products Administration of China (Z44020043). It is composed of Huang Qi (Astragalus mongholicus Bunge), San Qi (Panax notoginseng (Burkill) F. H. Chen), Ren Shen (Talinum paniculatum (Jacq.) Gaertn), Zhen Zhu (Pearl layer powder) and Niu Huang (Calculus bovis). An increasing volume of research has indicated that WNA capsule has a therapeutic effect on duodenal ulcers (Wang, 2017, Shi, 2019). Zeng and colleagues revealed that WNA capsules are safe and efficacious in the treatment of ulcerative colitis (UC) (Zeng MC, 2016), suggesting that WNA capsules may play a positive role in the repair of intestinal mucosal injury. However, the molecular mechanisms need to be explored in depth. In this study, we evaluated the influence of WNA on the intestinal injury rat model induced by indomethacin and explored the possible protective mechanisms in vivo and in vitro.

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