Kim Minjun, Song Young Mi, Yoon Kyung Jae, Hong Yurim, Park Jung Ho, Kim Yoo Kyung, Kim Juhee, Sohn Chong Il
Department of Gastroenterology, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University School of Medicine, Gyeonggi-do, Republic of Korea.
Institute of Medical Research, Samsung Kangbuk Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
PLoS One. 2025 Jun 27;20(6):e0316686. doi: 10.1371/journal.pone.0316686. eCollection 2025.
BACKGROUND/AIMS: Diabetes is associated with various gastrointestinal disorders, including altered gastric emptying, which may be rapid, slow, or transient. These alterations can significantly influence gastrointestinal symptoms and directly influence blood glucose levels. DA-9701 (motilitone), a prokinetic agent derived from Corydalis tuber and Pharbitis seed, is employed in Korea to manage functional dyspepsia due to its anti-inflammatory and gastrointestinal motility-enhancing properties. This study aims to investigate the potential of DA-9701 in addressing altered gastric emptying and glycemic control in diabetic rats, thereby validating its broader clinical utility.
MATERIALS/METHODS: Diabetes mellitus was induced in rats by streptozocin injection (65 mg/kg, i.p.). Following the onset of diabetes, rats received daily oral administration of DA-9701 for 2 weeks. Gastric emptying rates for liquid and solid meals were measured using plasma acetaminophen levels and residual food mass, respectively. Oral glucose tolerance tests (OGTT), insulin levels, and oxidative stress markers (malondialdehyde [MDA], Ogg1, Gpx, Cat) were assessed. Western blotting and qPCR were used to evaluate the expression of ERK1/2, c-Kit, and proliferating cell nuclear antigen (PCNA) in gastric tissue.
Diabetic rats exhibited significantly accelerated gastric emptying (liquid GE AUC: + 45.2%; solid GE: + 23.1%, p < 0.01) and elevated blood glucose (327.4 ± 22.8 mg/dL vs. 96.2 ± 10.1 mg/dL in controls, p < 0.001), accompanied by increased oxidative stress markers and expression of c-Kit, ERK1/2, and PCNA. DA-9701 treatment normalized gastric emptying rates (solid GE restored to 55.8%, p < 0.05), reduced MDA, Ogg1, Gpx, and Cat expression, and significantly downregulated ERK1/2, c-Kit, and PCNA. Moreover, insulin secretion increased 2.1-fold in DA-9701-treated diabetic rats (p < 0.05), resulting in improved glucose tolerance (OGTT AUC reduction: -24.6%, p < 0.01).
DA-9701 normalized gastric emptying and glycemic control while reducing the expression of ERK1/2, c-Kit, and PCNA, which are elevated in diabetic gastric tissues. These findings highlight the dual therapeutic potential of DA-9701 in regulating both gastrointestinal motility and glycemic variability in diabetes, warranting further investigation in clinical settings.
背景/目的：糖尿病与多种胃肠道疾病有关，包括胃排空改变，其可能是快速、缓慢或短暂的。这些改变可显著影响胃肠道症状并直接影响血糖水平。DA-9701（莫替林）是一种从延胡索块茎和牵牛子中提取的促动力剂，因其具有抗炎和增强胃肠动力的特性，在韩国被用于治疗功能性消化不良。本研究旨在探讨DA-9701在解决糖尿病大鼠胃排空改变和血糖控制方面的潜力，从而验证其更广泛的临床应用价值。
材料/方法：通过腹腔注射链脲佐菌素（65mg/kg）诱导大鼠患糖尿病。糖尿病发病后，大鼠每天口服DA-9701，持续2周。分别使用血浆对乙酰氨基酚水平和残余食物量测量液体和固体餐的胃排空率。评估口服葡萄糖耐量试验（OGTT）、胰岛素水平和氧化应激标志物（丙二醛[MDA]、Ogg1、Gpx、Cat）。采用蛋白质免疫印迹法和定量聚合酶链反应评估胃组织中ERK1/2、c-Kit和增殖细胞核抗原（PCNA）的表达。
糖尿病大鼠胃排空显著加速（液体胃排空曲线下面积：+45.2%；固体胃排空：+23.1%，p<0.01），血糖升高（327.4±22.8mg/dL，对照组为96.2±10.1mg/dL，p<0.001），同时氧化应激标志物以及c-Kit、ERK1/2和PCNA的表达增加。DA-9701治疗使胃排空率恢复正常（固体胃排空恢复至55.8%，p<0.05），降低了MDA、Ogg1、Gpx和Cat的表达，并显著下调了ERK1/2、c-Kit和PCNA。此外，DA-9701治疗的糖尿病大鼠胰岛素分泌增加了2.1倍（p<0.05），糖耐量得到改善（OGTT曲线下面积降低：-24.6%，p<0.01）。
DA-9701使胃排空和血糖控制恢复正常，同时降低了糖尿病胃组织中升高的ERK1/2、c-Kit和PCNA的表达。这些发现突出了DA-9701在调节糖尿病患者胃肠动力和血糖变异性方面的双重治疗潜力，值得在临床环境中进一步研究。
