Objective: This study investigated the alleviating effect of Micromeria biflora on hindgut mucosal damage in rats with type 1 diabetes.
Materials and Methods: 7-week-old male Sprague-Dawley rats were randomly divided into a control group (NC, n=15), a diabetic rat group (DC, n=15), and a Micromeria biflora treatment group (MbT, n=15, 300 mg/kg/day for 21 days). Changes in prostaglandin E2 (PGE2) concentration, cyclooxygenase-2 (COX-2) activity, and gene and protein expression of related signaling pathway components in the caecal mucosa were detected using enzyme-linked immunosorbent assay (ELISA), PCR, and Western blot, respectively.
Results: Compared with the DC group, M. biflora treatment significantly increased mRNA expression levels of CCND2 (1.4-fold, p<0.05) and MKI67 (1.9-fold, p<0.05), and increased protein expression of CCND2 (1.7-fold, p<0.05) and Sox9 (1.6-fold, p<0.05). It elevated β-defensin protein levels (40% increase, p<0.05) and interleukin-10 (IL-10) content (60% increase, p<0.05), and enhanced COX-2 activity (35% increase, p<0.05) as compared to the DC group. Treatment also increased local PGE2 content (75% increase, p<0.05) and membrane prostaglandin receptor 4 (EP4) levels (2.3-fold, p<0.05) as compared to the DC group. Furthermore, it upregulated epidermal growth factor receptor (EGFR) mRNA expression (1.5-fold, p<0.01) and increased protein abundances of phosphorylated CREB (pCREB) (2.0-fold, p<0.05) and phosphorylated AKT (pAKT) (1.8-fold, p<0.05) as compared to the DC group. No significant change in phosphorylated ERK (pERK) was observed.
Conclusion: M. biflora ameliorates diabetic hindgut injury by specifically activating the PGE2/EP4 signaling axis, evidenced by increased COX-2 activity (35%), PGE2 synthesis (75%), and EP4 receptor levels. This activation drives downstream phosphorylation of CREB and AKT, ultimately promoting epithelial proliferation and enhancing mucosal barrier function.