Paeoniflorin Alleviates Abnormalities in Rats with Functional Dyspepsia by Stimulating the Release of Acetylcholine

Abstract

Introduction: Paeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD.

Materials and methods: In this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances.

Results: We found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated.

Discussion: These results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.

Keywords: acetylcholine; functional dyspepsia; gastric function; paeoniflorin.

Figure 1

Paeoniflorin promotes gastric emptying, gastric accommodation and gastric sensitivity in FD rats. Rats were fasted for 18 h and then orally administered 0.2mL of 0.1% iodoacetamide (IA) or subcutaneously administered clonidine (CD) at a dose of 100 μg/kg. Effects of 15 or 30 mg/kg of paeoniflorin on (A) delayed gastric emptying, (B) gastric accommodation, and (C) gastric sensibility were assessed (n = 6/group). Values are mean ± SD. ^#p < 0.05 vs sham group; *p < 0.05 vs control group.

Figure 2

Paeoniflorin stimulates the release of acetylcholine (ACh) in FD rats. (A) Stomach-derived and (B) hypothalamus-derived acetylcholinesterase (AchE) activities were measured by paeoniflorin administration at dose of 15 or 30 mg/kg (n = 6/group). (C) The serum level of acetylcholine (ACh) was investigated (n = 6/group). Values are mean ± SD. ^#p < 0.05 vs sham group; *p < 0.05 vs control group.

Figure 3

Paeoniflorin regulates the levels of ghrelin and cyclo-oxygenase-2 (COX-2) in the stomach of FD rats. (A) Immunofluorescence images for ghrelin in the stomach were shown and (C) corresponding immunofluorescence intensity was quantified (n = 6/group). (B) Immunofluorescence images for COX-2 in the stomach was shown and (D) corresponding immunofluorescence intensity was quantified (n = 6/group). Red cells were positive for ghrelin and COX-2. Bars = 200 μm.

Figure 4

Paeoniflorin ameliorates the impaired gastrointestinal mucosa in FD rats. (A) Effects of paeoniflorin on adhesion proteins, including occluding, Zona Occludens-1 (ZO-1) and E-cadherin, in the duodenal mucosa were assessed by Western blotting (n = 6/group). (B) Quantitative immunofluorescence analysis was used to detect the expression of occludin. Bars = 33 μm. Values are mean ± SD. ^#p < 0.05 vs sham group; *p < 0.05 vs control group.