Abstract
Background: Compared to the general population, diabetic patients experience more frequent episodes of gastrointestinal (GI) motility dysfunction, owing to the disruption of functional innervations. DA-9701 is a new prokinetic agent formulated from the extracts of Pharbitidis semen and Corydalis tuber. Aim: To investigate the effect of DA-9701 on GI motility in an animal model of streptozotocin (STZ)-induced diabetes. Methods: Diabetes was induced in mice by intraperitoneal injection of STZ (40 mg/kg of body weight in 0.1 M citrate buffer) for 3 days. Diabetic mice were divided into four groups and administered DA-9701 in different doses (1, 3, and 10 mg/kg) or placebo for 2 weeks. Intestinal transit was assessed using charcoal meal movement. GI isometric contraction was measured by applying an isometric force transducer on a circular muscle strip of the antrum, ileum, and proximal colon of sacrificed mice. Gastric emptying rate was evaluated by measuring the dye percentage remaining in the stomach relative to the total dye amount recovered in a standardization group of mice. Results: Body weight and antral and small intestinal motility were less in diabetic mice than in control mice, and colonic motility was similar in both. DA-9701 showed a dose-dependent increase in the amplitude of spontaneous phasic contractions in the antrum, ileum, and colon in diabetic mice without influencing body weight or blood glucose levels. The degree of improvement was comparable between diabetic and control mice. Intestinal transit was significantly more delayed in diabetic mice than in controls (43 ± 7% vs. 67 ± 8%, p < 0.05); however, DA-9701 restored the delayed intestinal transit more effectively compared to placebo (75% vs. 50%). The gastric emptying rate was significantly more delayed in diabetic mice than in controls (43 ± 10% vs. 62 ± 12%, p < 0.05), and was improved by DA-9701 in a dose-dependent manner (50%, 55%, and 60% in mice treated with 1, 3, and 10 mg/kg of DA-9701, respectively, vs. 43% in placebo-treated and 60% in control mice). Conclusions: DA-9701 improved GI contractility without affecting blood sugar and body weight in diabetic mice. DA-9701 could improve the decreased GI motility and clinical symptoms in progressive diabetic patients.
Highlights
Functional gastrointestinal (GI) disorders occur more frequently in patients with diabetes than in the general population
We investigated the effect of DA-9701 on gastrointestinal motility, the intestinal transit, and gastric emptying rate in a streptozotocin (STZ)-induced diabetic mouse model
Two weeks after completion of the 3-day treatment with STZ or citric acid buffer, STZ-induced diabetic mice showed significantly higher blood glucose levels and lower body weight compared to normal controls (p < 0.05, Figure 2)
Summary
Functional gastrointestinal (GI) disorders occur more frequently in patients with diabetes than in the general population. Longstanding diabetes induces GI motility dysfunction via the disruption of nerve functions regulating the motility of the gut, which causes incomplete emptying of the different sections of the gastrointestinal tract. This process leads to gastroenteropathy, a composite disorder of the esophagus, stomach, small intestine, and colon [1]. DA-9701 is a new prokinetic agent formulated from the extracts of Pharbitidis semen and Corydalis tuber [4] This medicine, which is known to function as a 5-HT1A agonist, 5-HT4 agonist, and 5-HT3 partial antagonist, was developed for the treatment of functional dyspepsia [4,5,6]. Corydalis tuber is known to be effective in adjusting mild depression, severe nerve damage, tremors, and intestinal spasm [7]
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