To explore the efficacy and possible mechanism of Xingpi Capsule (醒脾胶囊) in the treatment of functional dyspepsia (FD).

Sixty SPF grade rats were randomly divided into normal group, model group, low-dose Xingpi Capsule group［0.135 g/ (kg·d) ］, high-dose Xingpi Capsule group［0.54 g/ (kg·d) ］and domperidone group［3 mg/ (kg·d) ］, with 12 rats in each group. Except for the normal group, which was given 0.2 mL of 2% sucrose by gavage, the other groups were used to prepare the functional dyspepsia rat models by gavage with iodoacetamide for 6 consecutive days. Then the rats were normally fed until the 8th week. Starting from the 8th week, the normal group and the model group were given the same volume of distilled water by gavage, while the treatment groups were given the corresponding medication by gavage for one week. The macroscopic signs, gastric emptying rate, small intestine propulsion rate, serum levels of vasoactive intestinal peptide (VIP) and substance P (SP) were detected by using enzyme-linked immunosorbent assay (ELISA). The morphology of gastric and duodenal tissues were observed using hematoxylin eosin staining (HE). The ZO-1 protein expression was observed using immunohistochemistry method. The mRNA expressions of ZO-1 and Occludin were detected using polymerase chain reaction (RT-PCR), and Occludin protein expression was detected using Western blot (WB). The changes in the types and abundance of gut microbiota were analyzed through 16S rRNA sequencing.

Compared with the normal group, the model group showed a decrease in body weight, rat fur withered and discolored, reduced grip, decreased open field total pathway, gastric emptying rate and small intestine propulsion rate (P<0.01). The HE staining site showed disordered arrangement of goblet cells. ELISA results showed an increase in VIP content and a decrease in SP content (P<0.01), while immunohistochemistry results showed a decrease in ZO-1 expression (P<0.01) . PCR results showed a decrease in mRNA expressions of ZO-1 and Occludin (P<0.01), and WB result showed a decrease in Occludin protein expression. Compared with those in the model group, the mental state of the rats in the Xingpi Capsule groups and the domperidone group was significantly improved, with increased gastric emptying rate and small intestinal emptying rate (P<0.05, P<0.01) . ELISA results showed a decrease in serum VIP content and an increase in SP content (P<0.05, P<0.01) . Immunohistochemistry results showed an increase in ZO-1 expression (P<0.05, P<0.01) . RT-PCR results showed an increase in mRNA expressions of ZO-1 and Occludin (P<0.05, P<0.01) . WB results showed an increase in Occludin protein expression (P<0.01), and high-dose Xingpi Capsule group had a significant therapeutic effect on the rats. 16S rRNA sequencing analysis showed significant changes in the overall structure of the gut microbiota in the model group compared to those in the normal group. Compared with that in the model group, the overall structure of gut microbiota in the high-dose Xingpi Capsule group and the domperidone group was closer to that in the normal group, with decreased Chao1 and Shannon indices (P<0.01) . Through species composition analysis, the relative abundance of Firmicutes phylum in the model group decreased compared to that in the normal group. Compared with that in the model group, the relative abundance of Firmicutes phylum increased in the high-dose Xingpi Capsule group and the domperidone group. The significant difference analysis among groups found that the high-dose Xingpi Capsule group had a positive effect on the homeostasis of intestinal microbiota.

Xingpi Capsule can improve the damage of duodenal mucosal barrier and regulate the steady state of intestinal microbiota to achieve the effect of treating functional dyspepsia.