• 대한한방내과학회지
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• 제43권6호
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• pp.1162-1185
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• 2022

Purpose: We examined the effects of Dansam (Salvia miltiorrhiza Bunge, SM) and Dansam-eum (DSE) on gastroesophageal reflux disease (GERD) and reflux esophagitis by comparing the inhibitory effects of SM and DSE with the representative treatment of PPI Omeprazole to determine if the effects of the prescription DSE based on Korean medicine are better than those of a single-use of SM. Methods: We performed experiments using both animal models and cancer cells. Results: Comparison of SM and DSE with PPI in the animal model tests revealed that the effects were superior for SM and DSE than for PPI in all categories (8-OHdG, p-IκB, PAR2, COX-1, cathelicidin, p-JNK, Caspase 3, ATP6V1B1, GRPR, serotonin, and NPY). In three categories (COX-1, serotonin, and NPY), SM and DSE showed superior results over the Controls. In the animal model tests, DSE was superior to SM in all categories except for serotonin. The anti-cancer effects observed in cancer cell tests revealed that SM and DSE had meaningful results in terms of cytotoxicity and cell movement rate, as well as in cancer cell apoptosis. Conclusions: We confirmed that SM and DSE can have effects on reflux esophagitis through the regulation of oxidative stress, inflammation, mucosal protection, apoptosis, proton pumping, and the enteroendocrine system in the stomach and esophagus. We also confirmed that SM and DSE have superior effects to those of PPI on all aspects, especially gastric mucosa protection and enteroendocrine system control. We also confirmed that SM and DSE have anti-cancer effects. Above all, we confirmed that DSE has superior effects on almost all aspects compared to using SM alone.

• 대한수의학회지
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• 제30권2호
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• pp.129-143
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• 1990

In the present paper, the distribution, relative frequences and cell types of endocrine cells in the gastrointestinal tract of the frog (Rana dybowskii) during the hibernating and the active phase were examined by light and electron microscopy. The results obtained are summarized as follow: The reactive cells for Grimelius were frequently found in the gastrointestinal tract, whereas the reactive cells for Hellman-$Hellerstr{\hat{o}}m$ were found numerous in the fundus and pylorus of stomach, a few in the duodenum and lower small intestine, and very few in the rectum during both phases. No reactive cells for Masson-Fontana were found in the gastrointestinal tract during both phases. Elecron microscopically, 4 types of endocrine cells in the fundus of the stomach, 3 types in the pylorus of the stomach and duodenum, and 1 type in the lower small intestine and rectum, respectively, were identified during the hibernating phase. In the active phase, 3 types of endocrine cell in the fundus of the stomach, 2 types in the pylorus of the stomach and duodenum, and 1 type in the lower small intestine and rectum were observed, respectively. In the hibernating phase, more cytoplasmic granules and various types of endocrine cells were generally found than in the active phase.

• Natural Product Sciences
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• 제25권2호
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• pp.165-171
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• 2019

Although the functions of a standardized extract of Gingko biloba leaves (EGb $761^{(R)}$) has been reported with regard to neurobiological properties, no attention has been paid to the impact of EGb $761^{(R)}$ on the neuronal regulation of energy homeostasis. To evaluate the hypothesis that EGb $761^{(R)}$ affect the secretion of peptide tyrosine tyrosine (PYY) and the activation of free fatty acid receptor 4 (FFA4), which are involved in the neuronal circuitries that control energy homeostasis by inducing the transfer of information about the influx of energy to the brain, we examined whether EGb $761^{(R)}$ can stimulate PYY secretion in the enteroendocrine NCI-H716 cells and if EGb $761^{(R)}$ can activate FFA4 in FFA4-expressing cells. In NCI-H716 cells, EGb $761^{(R)}$ stimulated PYY secretion and the EGb $761^{(R)}$-induced PYY secretion was involved in the increase in intracellular $Ca^{2+}$ concentration and the activation of FFA4. Furthermore, in FFA4-expressing cells, EGb $761^{(R)}$ activated FFA4. These results suggest that EGb $761^{(R)}$ may affect the control of energy homeostasis via the regulation of PYY secretion and FFA4 activation.

• 한국동물학회지
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• 제37권4호
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• pp.478-487
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• 1994

The developmental changes of three enteroendocrine cells, i.e. gastrln, somatostatin and serotonin, of gastric and small intestinal mucosa in pre- and postnatal rat were examined by peroxidase-antiperoxidase (PAP) method. In the course of development, gastrin cells were obsenred in the pyloric gland region and the whole part of small intestine, while somstostatin and serotonin cells in the whole gastric gland region and small intestine. More entroendocrine cells were detected in the pyloric gland region and duodenum than in the other portion. In the stomach, gastrin, somatostatin and serotonin ceils were first obsenred in the pyloric Bland region on 17, 19 and 19 days of gestation respectively. The small intestinal gastrin and serotonin cells were first appeared in the duodenum and iriunum on 17 and 15 days of gestation respectively, and somatostBtin cells in duodenum on 17 days of gestation. The number of cells examined from the stomach were increased from fetal to weanling period and showed a decrease during adult period: the notable increase was shown at the end of suckling period or at early weanling period. The cells of the small intestine increased from fetal to suckling period, especially, these cells markedly increased at the end of fetal period or at early suckling period, and decreased from weanling period. The shape of these cells was oval or fusiform during fetal period. In the stomach, most of gastrin cells turned out to be oval and open-type from suckling period, while the remaining two tripes of cells were oval and open- or closed-type. In the small intestine, 311%Ves of cells examined were changed to fusiform and open-type from the end of fetal period. Three types of cell were distributed over the stratified epithelium on 15 and 17 days of gestation. In the stomach, these cells were distributed lower gastric pit and gland from the following fetal period, and were detected mainly on the upper part of gland from suckling period, and then obsenred on the whole part of gland. In the small intestine, most of cells distributed over only between epithelium of villi on 19 days of gestation, increased in number on the crypt from following fetal period, and also observed abundantly in the crypt at adult period.

• Food Science and Biotechnology
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• 제15권1호
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• pp.19-23
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• 2006

Effects of cheonggukjang on immunohistochemical reactions in gastrointestinal (GI) tract of rats were investigated. $CD4^+/CD8^+$ immunoreactive cells of cheonggukjang-fed diet groups were more strongly stained in lamina propria of mucosa and submucosa than those of basal diet group. Universal nitric oxide synthase immunoreactive density in colon was mildly stained in surface epithelium and mucous secretory gland, and strongly stained in submucosa and myenteric plexus in muscle layers of all cheonggukjang-fed diet groups. Protein kinase C-${\alpha}$ immunoreactive cells in colons of 15 and 25% cheonggukjang-fed diet groups were more strongly stained in mucosa, submucosa, and muscle layers than those of basal diet group. These results indicate mucosal immune activity, gastrointestinal motility, blood circulation, and physiological activities of enteroendocrine cells in GI tract could be increased with cheonggukjang intake.

• 생명과학회지
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• 제22권5호
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• pp.621-626
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• 2012

초파리는 발생과 질병연구를 위한 모델 곤충으로 널리 이용되어 왔다. 본 연구에서도 초파리를 모델곤충으로 한 장질환 연구의 일환으로 다양한 병원균 감염 및 장질환 유발시 어떻게 장줄기세포가 작용하는지를 이해하기 위해 초파리 장세포의 일차배양 방법을 확립하였다. 초파리 성충으로부터 장을 해부하고 다양한 효소를 처리하여 장세포를 분리한 후 배양하였다. 배양세포의 생존여부는 현미경 검경 및 MTS assay에 의해 확인한 결과 배양 후 9일째 최대 증식되었고 14일까지 생존함을 확인할 수 있었다. 또한 장줄기세포 및 장내분비세포의 존재도 immunostaining에 의해 확인하였다. 따라서 본 연구에서 구축된 초파리 일차배양 장세포는 다양한 유전자에 의한 장줄기 세포 조절연구뿐만 아니라 장에서 발생하는 다양한 질병을 연구하는 도구로 매우 유용할 것으로 추측된다.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.219-225
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• 2022

Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca²⁺ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na⁺/Ca²⁺ exchanger (rNCX) in Ca²⁺ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca²⁺ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca²⁺ was ceased by substituting extracellular Na⁺ with Li⁺ or NMG⁺. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca²⁺ oscillation. Type 1 Na⁺/Ca²⁺ exchanger (NCX₁) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca²⁺ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.

• 동의생리병리학회지
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• 제26권2호
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• pp.166-174
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• 2012

To determine the effects of Mahaengeuigam-tang(MHEGT) on obesity, the obesity-related factors (gastrin, CGRP, ghrelin, glucagon-like peptide-1, insulin, orexin, leptin, serotonin, NPY) were investigated in the stomach, pancreas, brain of mice by immunohistochemical methods for 4 weeks after Mahaengeuigam-tang(MHEGT) administration. The change of boy weight decreased in MHEGT administered group than that of control group. The immunohistochemical density of the gastrin and CGRP positive cells on pylorus of stomach increased in MHEGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach decreased in MHEGT administered groups than that of control group. The immunohistochemical density of GLP-1 in the pancreas decreased in MHEGT administered group than that of control group. The immunohistochemical density of insulin positive cells in the pancreas decreased in MHEGT administered group than that of control group. The immunohistochemical density of orexin and NPY positive neurons in the diencephalon was slightly stronger in MHEGT administered group than that of control group. The immunohistochemical density of serotonin and leptin positive neurons was stronger in MHEGT administered group than that of control group. These results demonstrate that Mahaengeuigam-tang(MHEGT) increased the immunohistochemical density of factors related to appetite inhibitors, and decreased the immunohistochemical density of factors related to stimulator of food intake in stomach, pancreas and brain.

• Molecules and Cells
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• 제44권7호
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• pp.458-467
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• 2021

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca²⁺ flux via coupling to Gα_i and Gα_q families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gα_q/11 and Gα_12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

• BMB Reports
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• 제57권3호
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• pp.149-154
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• 2024

The stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis.