Protective effect and mechanisms of action of Mongolian medicine Sulongga-4 on pyloric ligation-induced gastroduodenal ulcer in rats

摘要

BACKGROUND Sulongga-4(SL-4)is a herbal formula used in traditional Mongolian medical clinics for the treatment of peptic ulcers and gastroenteritis,even though its pharmacological mechanism has not been well characterized.AIM To evaluate the protective effect and identify the mechanisms of action of SL-4 on gastroduodenal ulcer induced by pyloric ligation(PL)in rats.METHODS PL was performed to induce gastric and duodenal ulcers in rats,which were then treated with oral SL-4(1.3,2.6,or 3.9 g/kg per day)for 15 d.PL-induced gastroduodenal ulceration.Therapeutic effects were characterized by pathological and histological evaluations and inflammatory indicators were analyzed by enzyme-linked immunosorbent assay.Microarray analyses were conducted to identify gene expression profiles of gastroduodenal tissue in PL rats with or without SL-4 treatment.The candidate target genes were selected and verified by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RESULTS SL-4 decreased histopathological features in the PL-induced ulcerated rats.SL-4 significantly (P < 0.05) decreased expression of tumor necrosis factor-α,interleukin (IL)-1β, IL-6, endotoxin, platelet-activating factor, and increasedprostaglandin E2 and epidermal growth factor in ulcer tissue. Microarray analysiswas used to identify a panel of candidate target genes for SL-4 acting on PLinducedulceration. Genes included some complement and coagulation cascadeand retinol metabolism pathways that are closely associated with inflammatoryresponses and gastric mucosal protective mechanisms. qRT-PCR showed thataltered expression of the selected genes, such as CYP2b2, UGT2b1, A2m, andMASP1 was consistent with the microarray results.CONCLUSIONSL-4 exerts protective effects against PL-induced gastroduodenal ulcers viareducing inflammatory cytokines and elevating expression of gastric acidinhibitory factors. Downregulation of CYP2b2 and UGT2b1 genes in retinolmetabolism and upregulation of A2m and MASP1 genes in the complement andcoagulation cascades pathways are possibly involved in SL-4-mediated protectionagainst gastroduodenal ulcer.