{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:36:00Z","timestamp":1774330560481,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 \u00b1 7% vs. 67 \u00b1 8%, p &lt; 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 \u00b1 10% vs. 62 \u00b1 12%, p &lt; 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.<\/jats:p>","DOI":"10.3390\/jcm10225282","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"5282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7693-6601","authenticated-orcid":false,"given":"Changyoon","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Hospital, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rari","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaemin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangsoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Hwa","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul 07804, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-4443","authenticated-orcid":false,"given":"Ok-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Division of Gastroenterology, Gyeongsang National University Hospital, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2004.09.055","article-title":"American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis","volume":"127","author":"Parkman","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_2","first-page":"1","article-title":"Diabetic Gastroparesis: Principles and Current Trends in Management","volume":"9","author":"Krishnasamy","year":"2018","journal-title":"Diabetes Ther. Res. Treat. Educ. Diabetes Relat. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2337\/diab.35.7.733","article-title":"Diabetic autonomic neuropathy in BB rat. Ultrastructural and morphometric changes in parasympathetic nerves","volume":"35","author":"Yagihashi","year":"1986","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4062\/biomolther.2012.096","article-title":"DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia","volume":"21","author":"Kwon","year":"2013","journal-title":"Biomol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/j.1440-1746.2011.06924.x","article-title":"Effects of DA-9701, a novel prokinetic agent, on gastric accommodation in conscious dogs","volume":"27","author":"Kim","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_6","first-page":"836","article-title":"Gastroprokinetic effects of DA-9701, a new prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber","volume":"15","author":"Lee","year":"2008","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"140","DOI":"10.5009\/gnl.2014.8.2.140","article-title":"Effects of DA-9701, a novel prokinetic agent, on phosphorylated extracellular signal-regulated kinase expression in the dorsal root ganglion and spinal cord induced by colorectal distension in rats","volume":"8","author":"Lee","year":"2014","journal-title":"Gut Liver"},{"key":"ref_8","first-page":"291","article-title":"A Novel Pacemaker Mechanism Drives Gastrointestinal Rhythmicity","volume":"15","author":"Sanders","year":"2000","journal-title":"News Physiol. Sci. Int. J. Physiol. Prod. Jt. By Int. Union Physiol. Sci. Am. Physiol. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3748\/wjg.15.25","article-title":"Gastroparesis: Current diagnostic challenges and management considerations","volume":"15","author":"Waseem","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1053\/j.gastro.2008.09.003","article-title":"Heme Oxygenase-1 Protects Interstitial Cells of Cajal From Oxidative Stress and Reverses Diabetic Gastroparesis","volume":"135","author":"Choi","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_11","first-page":"523","article-title":"Varied effects of experimental diabetes on the autonomic nervous system of the rat","volume":"54","author":"Kniel","year":"1986","journal-title":"Lab. Investig. A J. Tech. Methods Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.7326\/0003-4819-92-2-301","article-title":"Pathology of autonomic neuropathy in diabetes mellitus","volume":"92","author":"Duchen","year":"1980","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1007\/s00535-006-1909-8","article-title":"A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus","volume":"41","author":"Iwasaki","year":"2006","journal-title":"J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2982.2009.01365.x","article-title":"Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis","volume":"22","author":"Lin","year":"2010","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1053\/j.gastro.2005.12.027","article-title":"Reduced Stem Cell Factor Links Smooth Myopathy and Loss of Interstitial Cells of Cajal in Murine Diabetic Gastroparesis","volume":"130","author":"Vittal","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1183-e1105","DOI":"10.1111\/j.1365-2982.2009.01374.x","article-title":"Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia","volume":"21","author":"Kindt","year":"2009","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5056\/jnm18162","article-title":"Gastroparesis and Functional Dyspepsia: A Blurring Distinction of Pathophysiology and Treatment","volume":"25","author":"Kim","year":"2019","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11892-006-0073-0","article-title":"An update on autonomic neuropathy affecting the gastrointestinal tract","volume":"6","author":"Phillips","year":"2006","journal-title":"Curr. Diabetes Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2982.2010.01611.x","article-title":"Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress","volume":"23","author":"Chandrasekharan","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1111\/jgh.13807","article-title":"DA-9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study","volume":"32","author":"Kim","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/mds.28219","article-title":"Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson\u2019s Disease: PASS-GI Study","volume":"35","author":"Choi","year":"2020","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1136\/gut.11.12.989","article-title":"Studies of the effect of metoclopramide and apomorphine on gastric emptying and secretion in man","volume":"11","author":"Ramsbottom","year":"1970","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10059-009-0039-6","article-title":"Induction of pacemaker currents by DA-9701, a prokinetic agent, in interstitial cells of Cajal from murine small intestine","volume":"27","author":"Choi","year":"2009","journal-title":"Mol. Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"414","DOI":"10.5056\/jnm14117","article-title":"Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia","volume":"21","author":"Choi","year":"2015","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.3748\/wjg.v19.i27.4380","article-title":"Effect of DA-9701 on gastric emptying in a mouse model: Assessment by 13C-octanoic acid breath test","volume":"19","author":"Lim","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/nmo.12053","article-title":"Effect of DA-9701, a novel prokinetic agent, on stress-induced delayed gastric emptying and hormonal changes in rats","volume":"25","author":"Jung","year":"2013","journal-title":"Neurogastroenterol. Motil."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/22\/5282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:50Z","timestamp":1760167790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/22\/5282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":26,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jcm10225282"],"URL":"https:\/\/doi.org\/10.3390\/jcm10225282","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]}}}