• Journal of Ginseng Research
• /
• v.39 no.4
• /
• pp.314-321
• /
• 2015

Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re ($20-40{\mu}M$) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 50-[${\beta}-thio$]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive $K^{+}$ channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester ($100{\mu}M$), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium ($K^{+}$) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction.

• The Journal of Internal Korean Medicine
• /
• v.26 no.4
• /
• pp.761-766
• /
• 2005

Objectives : 본 연구는 암환자의 위장관 기능장애를 개선시킬수 있는 보다 효과적인 약물개발의 일환으로 곽향 추출물의 장운동에 미치는 영향을 평가하기 위해 수행되어졌다. Methods : 생리적인 상태에서 곽향추출물이 장운동에 미치는 영향을 알아보기 위해 장운동촉진제인 carbachol과 곽향추출물을 실험쥐들에게 투여후 15분후 charcoal meal을 먹여서 charcoal meal의 소장내 통과 정도를 비교 측정하였다. 또, loperamide, scopolamine, nicotine으로 장운동을 억제시켜 놓은 실험쥐들에 15분 간격으로 곽향 추출물과 charcoal meal을 먹인 후 역시 charcoal meal의 소장내 통과 정도를 비교 측정하였다. Results : 곽향 추출물은 생리상태에서는 장운동에 영향을 미치지 않았다. 곽향추출물은 loperamide와 scopolamine으로 유발된 장운동 억제상태에 대하여 부분적으로 영향을 끼쳤다. 그러나 nicotine으로 유발된 상태에 대해서는 영항을 끼치지 않았다. Conclusion : 곽향 추출물은 소화관 기능부전 완화에 효과적으로 작용하는 천연물이라 추론할 수 있다.

• The Korean Journal of Physiology and Pharmacology
• /
• v.6 no.6
• /
• pp.311-317
• /
• 2002

This study was performed to investigate the pancreatic exocrine dysfunction in streptozotocin- induced diabetic rats. Changes in pancreatic enzymes secretion and in pancreatic enzymes content were observed. The output and the tissue content of amylase were significantly reduced in diabetic rats, while the output and the content of lipase were increased. Plasma secretin and cholecystokinin (CCK) concentrations of diabetic rats were significantly increased compared to those of normal rats. The altered pancreatic exocrine function was abolished by the exogenous insulin administration. The exogenous insulin also restored the increased plasma secretin and CCK concentrations. From the above results, it is suggested that, in streptozotocin-induced diabetic rats, anticoordinated changes in pancreatic enzymes secretion as well as pancreatic enzymes content are attributable to insulin deficiency and that the insulin deficiency is responsible for the increased plasma concentrations of both secretin and CCK. However, it is not clear whether the elevated plasma secretin and CCK concentrations played a direct role in changes of pancreatic exocrine function.

• Journal of Chest Surgery
• /
• v.49 no.3
• /
• pp.151-156
• /
• 2016

Background: Survival of children experiencing cardiac arrest refractory to conventional cardiopulmonary resuscitation (CPR) is very poor. We sought to examine current era outcomes of extracorporeal CPR (ECPR) support for refractory arrest. Methods: Patients who were <18 years and underwent ECPR between November 2013 and January 2016 were including in this study. We retrospectively investigated patient medical records. Results: Twelve children, median age 6.6 months (range, 1 day to 11.7 years), required ECPR. patients' diseases spanned several categories: congenital heart disease (n=5), myocarditis (n=2), respiratory failure (n=2), septic shock (n=1), trauma (n=1), and post-cardiotomy arrest (n=1). Cannulation sites included the neck (n=8), chest (n=3), and neck to chest conversion (n=1). Median duration of extracorporeal membrane oxygenation was five days (range, 0 to 14 days). Extracorporeal membrane oxygenation was successfully discontinued in 10 (83.3%) patients. Nine patients (75%) survived more than seven days after support discontinuation and four patients (33.3%) survived and were discharged. Causes of death included ischemic brain injury (n=4), sepsis (n=3), and gastrointestinal bleeding (n=1). Conclusion: ECPR plays a valuable role in children experiencing refractory cardiac arrest. The weaning rate is acceptable; however, survival is related to other organ dysfunction and the severity of ischemic brain injury. ECPR prior to the emergence of end-organ injury and prevention of neurologic injury might enhance survival.

• Food Science of Animal Resources
• /
• v.37 no.6
• /
• pp.931-939
• /
• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Clinical and Experimental Pediatrics
• /
• v.51 no.11
• /
• pp.1140-1146
• /
• 2008

Nocturnal enuresis is a heterogeneous disorder with various underlying pathophysiological mechanisms and causes a mismatch between the nocturnal bladder capacity and the amount of urine produced during sleep at night. It is associated with a simultaneous failure of conscious arousal in response to the sensation of bladder fullness. Generally, a complete history and physical examination, with a specific focus on the genitourinary, gastrointestinal, and neurologic systems, is sufficient to evaluate a patient with enuresis. The therapeutic focus is directed toward a differential approach based on the underlying mechanism and toward combination therapies such as alarm devices and desmopressin as well as anticholinergic agents and desmopressin. Children with increased nocturnal urine production usually have a good response to desmopressin therapy. Patients with a small bladder generally show a poor response to desmopressin treatment, but they would benefit more from combination therapy with enuretic alarm, urotherapy, and antimuscarinic agents in addition to desmopressin. Different types of bladder dysfunction, which result in a small nocturnal bladder capacity, probably contribute significantly to the pathogenesis of nocturnal enuresis, particularly in those with treatment failure and refractory symptoms. Because different clinical subgroups may show different responses to treatment, it is necessary to distinguish these subgroups before a decision on the specific treatment protocol can be made.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.2
• /
• pp.462-467
• /
• 2007

The radix of Pueraria thunbergiana BENTHAM (Leguminosae) is traditionally prescribed to attenuate the clinical manifestations of inner ear dysfunction and various clinical situations including fever, gastrointestinal disorders, skin problems, migraine headaches, lowering cholesterol and treating chronic alcoholism in Oriental Medicine. In the present study, we examined the effect of ethanol extract of P. thunbergiana radix (EPR) on cisplatin-mediated HEI-OC1 auditory cell death. In addition, to investingate the protection mechanism of EPR on free radicals. Treatment of EPR protected cells from cisplatin and reduced lipid peroxidation in a dose-dependent manner. Furthermore, EPR demonstrated significant scavenging activity against various free radicals, including superoxide radical, hydroxyl radical, hydrogen peroxide, and DPPH radical. These results indicate that EPR protects cisplatin-induced damages of HEI-OC1 cells through inhibition of lipid peroxidation and augmenting scavenging activities against free radials.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.4
• /
• pp.884-890
• /
• 2007

A mechanism of hair cell damage caused by noise and ototoxic agents is mediated through generation of free radicals and reactive oxygen species(ROS). It is known that most of animals have defense systems of ROS that protect against ROS, and the cochlea of animals also has ROS defense system, which appear efficient in detoxifying ROS generated under normal condition. This system includes several antioxidant enzymes such as superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase (GPX), and glutathione reductase(GR). The radix of Pueraria thunbergiana(P. thunbergiana) is traditionally prescribed to attenuate the clinical manifestation of inner ear dysfunction and various clinical situations including fevers, gastrointestinal disorders, skin problems, migraine headaches, lowering cholesterol, and treating chronic alcoholism in Oriental Medicine. In the present study, to investigate the protection mechanism of ${\beta}-sitosterol$ from P. thunbergiana on cisplatin cytotoxicity toward HEI-OC1, we measured the effects of ${\beta}-sitosterol$ on activities of SOD, CAT, GPX, and GR in cisplatin treated cells. SOD, CAT, GPX, and GR activities were significantly increased in the presence of 0.001-0.1 ${\mu}g/ml$ of ${\beta}-sitosterol$ compared to the control group. These results indicate that ${\beta}-sitosterol$ protects cisplatin-induced HEI-OC1 cell damage through increasing the antioxidant enzyme system such as SOD, CAT, GPX, and GR.

• Biomolecules & Therapeutics
• /
• v.27 no.6
• /
• pp.553-561
• /
• 2019

Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.5
• /
• pp.439-448
• /
• 2021

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4⁺ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ⁺ Th1 cells, IL-4⁺ Th2 cells, IL-9⁺ Th9 cells, IL-17⁺ Th17 cells, and Foxp3⁺ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.