Modified Shenqi compound alleviated constipation and inflammation in diabetic mice by regulating the miR-23a-3p/Nrf2 axis.

Abstract

Constipation is a prevalent gastrointestinal complication in patients with diabetes mellitus (DM), characterized by infrequent bowel movements and difficulty in defecation. Modified Shenqi Compound (MSQC), a traditional Chinese medicine (TCM) formulation, has demonstrated therapeutic efficacy against DM; however, its mechanisms in alleviating diabetic constipation remain unclear. This study investigates the effects and underlying mechanisms of MSQC in a mouse model of diabetic constipation. Diabetic mice with constipation were treated with MSQC, and various parameters including constipation symptoms, intestinal mucosal damage, inflammatory response, gut microbiota composition, and oxidative stress were evaluated. Additionally, miR-23a-3p antagomir was used to investigate the role of the miR-23a-3p/Nrf2 axis in mediating the effects of MSQC. The results showed that MSQC administration significantly ameliorated constipation symptoms, attenuated intestinal mucosal damage, and reduced inflammatory responses. Moreover, MSQC modulated the gut microbiota profile, notably decreasing the abundance of Cryptobacteroides while increasing that of Faecalibaculum, Vagococcus_B. In addition, MSQC inhibited intestinal oxidative stress via upregulating miR-23a-3p, which in turn promoted the expression of its downstream target, Nrf2. Crucially, the co-administration of a miR-23a-3p antagomir reversed the therapeutic benefits of MSQC, counteracting its improvements on constipation symptoms, intestinal mucosal injury, and inflammation. In conclusion, MSQC effectively alleviates diabetic constipation through a multi-targeted mechanism involving the activation of the miR-23a-3p/Nrf2 antioxidant pathway, reinforcement of the intestinal barrier, suppression of inflammation, and restoration of gut microbial homeostasis. Our findings provide a mechanistic basis for the clinical application of MSQC in treating diabetic constipation.