• The Journal of the Convergence on Culture Technology
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• v.10 no.3
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• pp.865-872
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• 2024

Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic motility, and these effects were prevented by Fruit and vegetable complex extracts(FVCE). In this study, the effects of FVCE on constipated male Sprague-Dawley rats induced by loperamide(3 mg/kg, s.c.,14 days) were investigated. Rats were randomly assigned to the normal control rats(regular diet), constipated rats(regular diet plus loperamide), constipated rats treated with 200 mg FVCE(regular diet supplemented with 200 mg/kg/day FVCE plus loperamide), constipated rats treated with 400 mg FVCE(regular diet supplemented with 400 mg/kg/day FVCE plus loperamide). There was less fecal excretion and lower fecal water content in loperamide-treated rats than in control rats. Oral administration of FVCE blocked the decrease of fecal excretion and fecal water content in the loperamide-treated rats. Mucus production of crypt cell and mucus contents at fecal and mucosa surface were reduced by loperamide-treated rat. But colonic crypt cell contained increased mucin in the FVCE treated group and mucus layer stained with alcian blue was significantly thicker in FVCE treated rats compared with in loperamide-treated rats. In isolated rat ileum, loperamide produced inhibition of ileal motility. Pretreatment with water extracts of FVCE in isolated rat ileum prevented inhibition by loperamide. These findings indicated that the FVCE was effective for alleviation of inhibition of colonic peristalsis by loperamide and that FVCE might be of value in the prevention of constipation.

• Biomedical Science Letters
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• v.18 no.3
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• pp.218-226
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• 2012

Dopamine is an enteric neurotransmitter that regulates gastrointestinal motility. This study was done to investigate whether dopamine modulates spontaneous pacemaker activity in cultured interstitial cells of Cajal (ICCs) from mouse using whole cell patch clamp technique, RT-PCR and live $Ca^{2+}$ imaging analysis. ICCs generate pacemaker inward currents at a holding potential of -70 mV and generate pacemaker potentials in current-clamp mode. Dopamine did not change the frequency and amplitude of pacemaker activity in small intestinal ICCs. On the contrary dopamine reduced the frequency and amplitude of pacemaker activity in large intestinal ICCs. RT-PCR analysis revealed that Dopamine2 and 4-receptors are expressed in c-Kit positive ICCs. Dopamine2 and 4 receptor agonists inhibited pacemaker activity in large intestinal ICCs mimicked those of dopamine. Domperidone, dopamine2 receptor antagonist, increased the frequency of pacemaker activity of large intestinal ICCs. In $Ca^{2+}$-imaging, dopamine inhibited spontaneous intracellular $Ca^{2+}$ oscillations of ICCs. These results suggest that dopamine can regulate gastrointestinal motility through modulating pacemaker activity of large intestinal ICCs and dopamine effects on ICCs are mediated by dopamine2 receptor and intracellular $Ca^{2+}$ modulation.

• Journal of Sasang Constitutional Medicine
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• v.27 no.2
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• pp.254-269
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• 2015

Objectives This study aimed to observe the effect of Taeumjowi-tang on the cisplatin-induced gastrointestinal dysfunctions in rats. Methods Four groups, each of 8 rats per group, were used in this study. Saline and distilled water treated control rats were intact vehicle control group. Delayed gastrointestinal motility was induced by intraperitoneal treatment of cisplatin 2mg/kg, once a week for 5 weeks(Cisplatin control group). Taeumjowi-tang aqueous extracts(TJ) were orally administered in a volume of 5ml/kg, once a day for 14 days from 4th cisplatin treatment(TJ group). Ondansetron 1mg/kg was subcutaneously treated, in a volume of 1ml/kg, as same as TJ(ondansetron group). We measured the body weights, intestinal charcoal transit ratio, fecal parameters, fundus MDA(malondialdehyde), GSH(glutathione) contents and SOD(superoxide dismutase), CAT(catalase) activities, TPH(tryptophanhydroxylase) and MAO(monoamine oxidase) activities, pyloric gastrin and serotonin contents with their immunoreactive cells, colonic serotonin-immunoreactive cells, the histopathology of pylorus, fundus mucosa and colon. Results 1) The body weight gains, the small intestinal charcoal transfer rates, the fecal parameters(numbers, weights and water contents) were increased in TJ, ondansetron group. 2) The inhibit of fundus antioxidant defense systems by cisplatin were decreased in TJ, ondansetron group. 3) The pyloric TPH activities were increased and the pyloric MAO activities were decreased in TJ group. 4) The pyloric gastric contents and the gastrin-immunoreactive cells were increased and the pyloric serotonin contents and the pyloric and colonic serotonin-immunoreactive cells were decreased in TJ group. 5) The pylorus atrophic changes and the gastric surface erosive damage regions by cisplatin were favorably inhibited by treatment of TJ group. Conclusions The results obtained in this study suggest that TJ favorably retarded the cisplatin related GI(gastrointestinal) dysfunctions and constipation through modulations of GI enterochromaffin cells, serotonin and gastrin-producing cells and antioxidative systems.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.669-675
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• 2018

Background/Aims Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs. Methods Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of $10{\mu}g/kg$ of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay. Results Different concentrations (1, 3, and $10{\mu}g/kg$) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF $10{\mu}g/kg$ was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model. Conclusions Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1227-1234
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• 2011

We investigated the immunostimulatory effects of doenjang, a famous Korean traditional food made from fermented soybean paste, on the immunohistochemical reaction in the gastrointestinal (GI) tract and immune response in mice. Male C57BL/6N mice (6 weeks-old) were divided into 4 experimental diet treatment groups and a basal diet (control) group, and fed with different diets for 4 weeks. The immunoreactive density of $CD4^+/CD8^+$ lymphocytes were strongly stained in the jejunum and colon in Group III. The immunoreactivity of universal nitric oxide synthase (uNOS) was strongly stained in the myenteric plexus in the colon of all doenjang-fedgroups (I, II and III). The colonic immunoreactive density of protein kinase C-${\alpha}$ (PKC-${\alpha}$) was strongly increased in Groups II and III, while that of stem-cell factor (c-kit) was increased in colonic mucosa of all doenjang-fedgroups (I, II and III) and especially increased in the colonic muscle layer of Group III. These morphological and immunological results indicated that the intake of doenjang could improve the mucosal immune reaction, gastrointestinal motility, blood circulation in the GI tract, and the immuneactivity of the body. These results provide experimental evidence about the health benefits of doenjang.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.333-338
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• 2000

We have examined whether bile acids can affect the electrical and mechanical activities of circular smooth muscle of canine colon and ileum, using isometric tension measurement or patch clamp technique. It was found that a dilution of canine bile $(0.03{\sim}2%\;by\;volume)$ enhanced or inhibited the amplitude of spontaneous contractions. An individual component of bile, deoxycholic acid (DCA) enhanced the frequency and amplitude of the spontaneous contractile activity at $10^{-6}\;M,$ while DCA at $10^{-4}\;M$ inhibited the contraction. Similarly, the response to cholic acid was excitatory at $10^{-5}\;M$ and inhibitory at $3{\times}10^{-4}\;M.$ Taurocholic acid at $10^{-4}\;M$ enhanced the amplitude of muscle contraction. Electrically, canine bile at 1% reversibly depolarized the colonic myocytes under current clamp mode. Bile acids also elicited non-selective cation currents under voltage clamp studies, where $K^+$ currents were blocked and the $Cl^-$ gradient was adjusted so that $E_{Cl}^-$ was equal to -70 mV, a holding potential. The non-selective cation current might explain the depolarization caused by bile acids in intact muscles. Furthermore, the bile acid regulation of electrical and mechanical activities of intestinal smooth muscle may explain some of the pathophysiological conditions accompanying defects in bile reabsorption.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.435-440
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• 2015

This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive $K^+$ channel blocker). However, neither $N^G$-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-${\alpha}$]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive $K^+$ channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.656-668
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• 2018

Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

• Journal of Neurogastroenterology and Motility
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• v.26 no.1
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• pp.106-116
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• 2020

Background/Aims Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1518-1524
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• 2008

Ponciri Fructus (PF), the immature fruit of Poncirus trifoliata, has been used for treatment of constipation in Korean traditional medicine. It has been reported that PF has a prokinetic effect on gastrointestinal tract, but little is known about the effect on colonic contraction. The aim of this study was to investigate the effect of PF on spontaneous contractions of proximal and distal colon in rats. The aqueous extract of PF was centrifuged and filtered and its supernatant was used for in vitro motility study. The removed colon from rats was divided into proximal and distal segments. Each segment was mounted in a 10 ml organ bath and measured the change of the spontaneous contraction with increasing dose (1, 5, 10, 50, 100, 500, $1000{\mu}g/ml$) of PF extract administration. Also the effect of PF on the spontaneous contraction was measured under treatment of atropine, acetylcholine (Ach), and tetrodotoxin (TTX). PF increased the spontaneous phasic contraction of distal colon dose dependently, but there was no change in proximal colon. The contractile response induced by PF in distal colon was lower than that of Ach and was partially blocked by atropine ($10^{-6}M$). TTX increased the spontaneous contraction and it was reinforced with Ach addition. But the extract of PF had no or little contractile effect of TTX in colon. PF increased spontaneous contractions selectively in distal colon. The prokinetic effect of PF may be due to enhancement of cholinergic related excitatory neural system.