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Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice

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 tub...

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Autores principales: Ha, Changyoon, Kim, Heejin, Cha, Rari, Lee, Jaemin, Lee, Sangsoo, Ryu, Jung-Hwa, Kim, Hyunjin, Lee, Ok-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623860/
https://www.ncbi.nlm.nih.gov/pubmed/34830563
http://dx.doi.org/10.3390/jcm10225282
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author Ha, Changyoon
Kim, Heejin
Cha, Rari
Lee, Jaemin
Lee, Sangsoo
Ryu, Jung-Hwa
Kim, Hyunjin
Lee, Ok-Jae
author_facet Ha, Changyoon
Kim, Heejin
Cha, Rari
Lee, Jaemin
Lee, Sangsoo
Ryu, Jung-Hwa
Kim, Hyunjin
Lee, Ok-Jae
author_sort Ha, Changyoon
collection PubMed
description 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.
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spelling pubmed-86238602021-11-27 Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice Ha, Changyoon Kim, Heejin Cha, Rari Lee, Jaemin Lee, Sangsoo Ryu, Jung-Hwa Kim, Hyunjin Lee, Ok-Jae J Clin Med Article 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. MDPI 2021-11-13 /pmc/articles/PMC8623860/ /pubmed/34830563 http://dx.doi.org/10.3390/jcm10225282 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ha, Changyoon
Kim, Heejin
Cha, Rari
Lee, Jaemin
Lee, Sangsoo
Ryu, Jung-Hwa
Kim, Hyunjin
Lee, Ok-Jae
Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title_full Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title_fullStr Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title_full_unstemmed Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title_short Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice
title_sort effect of da-9701 on the gastrointestinal motility in the streptozotocin-induced diabetic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623860/
https://www.ncbi.nlm.nih.gov/pubmed/34830563
http://dx.doi.org/10.3390/jcm10225282
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