• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.141-144
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• 1995

Serotonergic neurons in brainstem play important roles in the endogenous descending pain inhibitory system. To illucidate the involvement of glutamate receptors in the regulation of brainstem serotonergic neurons, we studied the effects of glutamate receptor agonists on 5-hydroxytryptamine(5-HT) release from cultured neurons of rat fetal (gestational age 14th day) brainstem. Cultured cells maintained for 10 days in vitro were stimulated for 30 minutes with agonists of glutamate receptor subtypes at 10-1,000 micromolar concentration. Glutamate (10-1,000 M) increased 5-HT release in a concentration-dependent manner. N-methyl-D-aspartic acid $(NMDA)(10-1,000\;{\mu}M)$ increased 5-HT release in a concentration-dependent manner. Non-NMDA receptor agonists, kainate and $AMPA(3-1,000\;{\mu}M)$ also concentration-dependently increased 5-HT release. These results suggest that both NMDA and non-NMDA receptors regulate 5-HT release from brainstem serotonergic neurons.

• Herbal Formula Science
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• v.28 no.1
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• pp.53-62
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• 2020

Objective : This study is accomplished in order to investigate the effect of banggibongnyeongtang on the immunohistological change in LPS-induced depression rats to confirm the histological result of the previous behavioral and biochemical effect. Methods : LPS 5 ㎍ was injected to lateral ventricle and experimental groups were administered BBT intraperitoneally. The concentration of 5-HT in the Medial Prefrontal Cortex, Striatum, Hippocampus, Amygdala was measured by ELISA. IL-1β, TNF-α mRNA and BDNF mRNA expression in the hippocampus was examined by RT-PCR. Result : BBT enhanced 5-HT concentration at all part of brain but no significantly difference at medial prefrontal cortex and striatum. LPS+BBT400 group increased 5-HT concentration significantly than LPS group at hippocampus and amygdala (p<0.05). BBT decreased IL-1β mRNA expression dose dependently but only with significantly decrease in LPS+BBT400 group than LPS group's in Hippocampus (p<0.05). But BBT did not decrease TNF-α mRNA expression significantly in Hippocampus. BBT increased the expression of BDNF mRNA at hippocampus and LPS+BBT400 group significantly increased comparing with LPS group does (p<0.05). Conclusion : It is postulated that the anti-depressant effect of BBT can be validated through the anti-inflammatory effect, 5-HT concentration increase, and the neuro-protective effect mediated by BDNF by combining the results of the previous report about the behavioral and biochemical effect.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.509-517
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• 2019

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through $5-HT_3$ receptors. Using a wholecell voltage clamp method, we recorded currents of $5-HT_3$ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. $EC_{50}$ of 5-HT on $5-HT_3$ receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of $5-HT_3$ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated $5-HT_3$ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit $5-HT_3$ receptor currents in a non-competitive manner with the mechanism of open channel blocking.

• YAKHAK HOEJI
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• v.53 no.4
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• pp.184-188
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• 2009

Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.

• Journal of Life Science
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• v.9 no.2
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• pp.82-85
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• 1999

The effects of ethanol on 5-hydrosytryptamine(5-HT3) receptor-mediated ion current were evaluated in whole-cell patch-clamp recordings from NCB-20 neuroblastoma cells. The physiologic and pharmacologic properties of 5-HT-activated ion current in NCB-20 cells indicated that it was mediated by 5-HT3 receptors. Ethanol(25-100mM) potentiated 5-HT3 receptor-mediated current in a concentration-dependent manner.

• Journal of Trauma and Injury
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• v.19 no.1
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• pp.14-20
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• 2006

Purpose: Although hypothermia has been used in many clinical situations, such as post cardiopulmonary resuscitation, stroke, traumatic brain injury, septic shock, and hemorrhagic shock, the mechanism by which it works has not been clearly elucidated. We aimed to evaluate the effect of hypothermia on the plasma nitric oxide (NO) concentration, lung iNOS expression, and histologic changes in intestinal ischemia-reperfusion (IR). Method: Male Sprague-Dawley rats were randomly divided into the hypothermia group (HT, n=8, $27{\sim}30^{\circ}C$) and the normothermia group (NT, n=8, $36{\sim}37^{\circ}C$). They underwent 30 min of intestinal ischemia by clamping the superior mesenteric artery, which was followed by 1.5 h of reperfusion. They were then sacrificed. The acute lung injury (ALI) score, the plasma NO concentration, and lung iNOS gene expression were measured. Results: Compared with the HT group, the NT group showed severe infiltrations of inflammatrory cells, alveolar hemorrhages, and interstitial hypertrophies in lung tissues. There were significant differences in the ALI scores between the NT and the HT groups ($8.7{\pm}1.5/HPF$ in NT vs $5.8{\pm}1.2/HPF$ in HT, p=0.008). Although the plasma NO concentration was slightly lower in the HT group, there was no significant difference between the two groups ($0.80{\pm}0.24{\mu}mol/L$ in NT vs $0.75{\pm}0.30{\mu}mol/L$ in HT, p=0.917). Lung iNOS gene expression was stronger in the NT group than in the HT group. The band density of the expression of iNOS in lung tissues was significantly increased in the NT group compared to the HT group ($5.54{\pm}2.75$ in NT vs$0.08{\pm}0.52$ in HT, p=0.002). Conclusions: This study showed that hypothermia in intestinal IR reduces inflammatory responses, ALI scores, and iNOS gene expression in lung tissues. There was no significant effect of hypothermia on the plasma NO concentration.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.9-18
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• 2018

Objectives : This study aimed to investigate the anti-ulcer effect of an standardized herbal extracts mixture of Inulae Flos and Paeoniae Radix (HT074) on acidified ethanol induced gastric injury and its potential mechanisms. Methods : Antioxidant activities of HT074 and its constituents were measured by DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging capacity. After the oral administration of HT074 at doses of 100, 300 mg/kg twice per day for 14 days, Gastric lesions were induced by oral administration of acidified ethanol in Sprague Dawley rats. Oxidative stress markers, such as super oxide dismutase (SOD) activity, concentrations of catalase (CAT) and glutathione (GSH) were measured in gastric mucosal tissues. Additionally, the expression of human mucin gene, Mucin 5AC (MUC5AC) mRNA in gastric mucosal tissues was measured. Results : HT074 showed dose dependent radical scavenging activities against DPPH and ABTS radicals. Oral administration of HT074 300 mg/kg for 14 consecutive days significantly decreased gastric lesions and histological damages induced by HCl/EtOH in rats. HT074 treatment significantly increased the activity of SOD (300 mg/kg) and concentration of GSH (100 and 300 mg/kg), however catalase concentration was not significantly increased. MUC5AC mRNA expression was significantly increased by HT074 100, 300 mg/kg treatment. Conclusions : HT074 protects the gastric mucosa from oxidative stress caused by acidified ethanol by increasing the activity of SOD, concentration of GSH and mucin biosynthesis. These findings suggest that HT074 could be an effective candidate for prevention and treatment of gastritis and gastric ulcer.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.295-301
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• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.27-31
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• 2010

Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L.), has been reported to suppress tumor growth. 4-hydroxychalcone and isobavachalcone are chalcone derivatives and they have similar structure with xanthohumol. In the present study, we investigated the cytotoxic activities of chalcone and its derivatives, 4-hydroxychalcone, xanthohumol, and isobavachalcone, in MCF-7 and adriamycin resistant MCF-7 (MCF-7/ADR) breast cancer cells and HT-1080 fibrosarcoma cells. In a cell viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reagent, chalcone and 4-hydroxychalcone decreased cell viability in HT-1080 cells, but not in MCF-7 and MCF-7/ADR cells. Isobavachalcone showed similar cytotoxicity in HT-1080 cells, and only limited cytotoxicity in MCF-7 and MCF-7/ADR cells at very high concentration (50 ${\mu}M$). In contrast, xanthohumol showed concentration-dependent cytotoxicity in MCF-7, MCF-7/ADR, and HT-1080 cancer cells. Taken together, the structure-activity relationship of chalcone and its derivatives indicate that chalcones may be valuable cytotoxic compounds against selective cancer types.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.149-153
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• 2014

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.