• Biomolecules & Therapeutics
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• 제12권3호
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• pp.151-156
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• 2004

This study was carried out to evaluate the putative anxiolytic-1ike effects of the aqueous extracts of Sanjoin-tang (SJIT) and its ingredients using the elevated plus maze (EPM) test in mice. SJIT consists of five herbs, namely, Zizyphi Spinosi Semen (roasted), Glycyrrhizae Radix, Cnidii Rhizoma, Anemarrhenae Rhizoma, and Hoelen. The aqueous extracts of SJIT and each herbal drug were orally administered to ICR mice, 1 hr before evaluating behavioral activity in the EPM test, respectively. Repeated treatments (for 3 days) of the aqueous extract of SJIT (400 mg/kg) significantly increased time-spend in the open arms and arms entries into the open arms in the EPM test. Zizyphi Spinosi Semen (400 mg/kg), an ingredient of SJIT, significantly increased timespent in the open arms and arm entries into the open arms (P < 0.05). However, the other ingredient of SJIT did not show any anxiolytic-like behaviors. In addition, the anxiolytic-like effects of Zizyphi Spinosi Semen were blocked by pindolol (lO mg/kg), a $5-HT_{1A}$ receptor antagonist. These results suggest that Zizyphi Spinosi Semen (roasted) as an ingredient of SJIT plays a crucial anxiolytic role, and it acts via the serotonergic nervous system.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.84-89
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.

• 동의생리병리학회지
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• 제27권2호
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• pp.225-232
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• 2013

Delayed gastrointestinal (GI) motility is frequent adverse effect associated with chemotherapy, and induced by serotonin releases from enterochromaffin cells. Ijintang-gamibang (IJG) is a digestive polyherbal formula has been traditionally used in Korea and consisted of 8 types of medicinal herbs. This study was conducted to determine whether or not IJG aqueous extracts can prevent delayed GI motility induced by the antineoplastic drug cisplatin chronically administered, once per week for five consecutive weeks (2 mg/kg). 200, 100 and 50 mg/kg of IJG extracts were orally administered, once a day for 14 days from fourth cisplatin treatment, and the changes in body weight gain, fecal parameters, gastrointestinal transit ratio and histopathology were observed. In addition, pylorus gastrin and serotonin contents were also measured with immunohistochemical observations of enterochromaffin cells contains gastrin and serotonin, as compared with ondansetron, a serotonin 5-HT3 receptor antagonist, 1 mg/kg. Cisplatin treatment related body weight decreases, delayed GI motility, decreases of fecal water contents were significantly and dose-dependently inhibited by oral treatment of IJG extracts, and they also inhibited the pylorus gastrin and serotonin changes induced by cisplatin treatment. The overall effects of IJG 100 mg/kg were similar to that of ondansetron 1 mg/kg. The present results supported that IJG aqueous extracts have favorable ameliorating effect on the delayed GI motility induced by chemotheraphy, modulated the GI enterochromaffin cells, serotonin and gastrin-producing cells with antioxidant effects. This effect of IJG may help improve accompanying gastrointestinal symptoms by chemotherapy.

• 동의생리병리학회지
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• 제18권4호
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• pp.1041-1054
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• 2004

Electroacupuncture (EA) has been reported to increase pain threshold, and to enhance the NK cell activity by up-regulation of IFN-γ and endogenous β-endolphin. For the purpose of understanding the molecular mechanism of EA stimulation, we analyzed the gene expression profile of rat hypothalamus, treated on Zusanli (ST36) with EA, in comparison with control group by oligonucleotide chip microarray (Affymetrix GeneChip Rat Neurobiology U34 Array) and real-time RT-PCR. Sprague-Dawley (S-D) male rats were stimulated at the Zusanli (ST36) acupoint in restriction holder. Simultaneously the control group was given only holder stress without EA stimulation. In order to prove the appropriateness of EA treatment, we measured spleen NK cell activity with standard 51Cr release assay. NK cell activity of EA group was significantly increased comparing to control group. The microarray and PCR results show that EA treatment up-regulates expression of genes associated with 1) nerve growth such as NGF induced factor A and VGF, 2) signal transduction such as 5HT3 receptor subunit, AMPA receptor binding protein and Na-dependent neurotransmitter transporter, and 3) anti-oxidation such as superoxide dismutase and glutathione S-transferase. In addition, the activity of the anti-oxidative enzyme, SOD of hypothalamus, liver and RBC was enhanced compared to that of control. The list of differentially expressed genes may implicate further insight on the mechanism of acupuncture effects.

• 동의신경정신과학회지
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• 제15권1호
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• pp.43-64
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• 2004

The aim of this study was to evaluate the effects of Jowiseungcheongtang compared with St. John's wort in the chronic mild stress(CMS) animal model of depression. Wistar rats were used for this study. The subjects were divided into 4 groups (Naive group: without CMS procedure, CMS-vehicle: water was administered during CMS procedure, CMS-Jowiseungcheongtang: Jowiseungcheongtang was administered after 5 weeks of CMS procedure, CMS-St. John's wort: St. John's wort was administered after 5 weeks of CMS procedure) During 9 weeks of CMS procedure, The change of the consumption of sucrose and the changes of weights were measured. After CMS procedure, Morris water maze test, open field test, elevated plus maze test and Western blotting were measured. The results were as follows. 1. The consumption of sucrose solution was significantly reversed in Jowiseungcheongtang group and relatively reversed in St. John's Wort group at 7 week. 2. In open field test, Neither Jowiseungcheongtang nor St. John's wort group showed statistically significant change of exploratory activity. In EPM test, St. John's Wort group showed significant decrease of total arm entry in comparison with Naive group. And Jowiseungcheongtang group was showed no significant change. 3. In Morris water maze test, St. John's Wort group showed significant increase in escape latency of the last Morris water maze trial. And in water maze probe test, there was no significant change. 4. St. John's Wort group showed relative increase in LP1 division of 5HT1A receptor compared with Naive group. Both St. John's Wort and Jowiseungcheongtang group showed relative increase in P2 division of GluRl compared with Naive group. These results suggest that Jowiseungcheongtang is as effective as St. John's Wort in the treatment of depression.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.213-218
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• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.

• 대한한방내과학회지
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• 제30권1호
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• pp.107-118
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• 2009

Objectives : This study was aimed to investigated the effect of Yijin-tang on gastric motility and its mechanism of action in normal intact and partial pyloric obstructed rats. Methods : Gastric emptying was measured by the number of glass beads expelled from the stomach (containing one hundred of glass beads. ${\phi}1mm$) in 1 hour or 2 hours after glass beads and test drugs (normal saline. Yijin-tang 90mg/kg. Yijin-tang 270mg/kg) administration in normal intact and partial pyloric obstructed rats. In another series of experiments to evaluate the mechanism of Yijin-tang 270mg/kg under delayed conditions, normal intact rats were treated with atropine sulfate (1mg/kg,s.c.), cisplatin (10mg/kg,i.p.), quinpirole HCI (0.3mg/kg,i.p.) and NAME (NG-nitro-L-arginine methyl ester. 75mg/ kg,s.c.), respectively. Partial pyloric obstructed rats were modified by wrapping the nonabsorbable rubber ring (D :6mm, W:4mm, T: 1mm) around the 1st portion of the duodenum for 8 weeks. The myoelectrical activity of the gastric smooth muscle was recorded by a bipolar electrode placed at the abdominal surface in normal intact and partial pyloric obstructed rats. The gastric myoelectrical activity was measured for 30 minutes before and after orogastric administration of each solution (normal saline, Yijin-tang 270mg/kg) and expressed as dominant frequency, percent of normogastria and power ratio. Results : Yijin-tang improved gastric emptying more than normal saline in normal intact(p<0.001) and partial pyloric obstructed rats(p=0.002). Under the delayed gastric emptying induced by atropine sulfate, cisplatin, quinpirole HCI and NAME. Yijin-tang enhanced gastric emptying significantly in the cisplatin treated group(p<0.001). but didn't in other treated groups. Administration of Yijin-tang 270mg/kg has no significant effect on the myoelectrical activity of the gastric smooth muscle in both normal intact rats and partial pyloric obstructed rats. Conclusions : Yijin-tang seems to stimulate the gastric motility through suppressing the 5HT3 receptor and promoting the antroduodenal flow. We expect that Yijin-tang would be effective especially in dysmotility-like functional dyspepsia with partial pyloric obstruction or the side effects of cisplatin such as nausea, vomiting, abdominal discomfort, and delay of gastric emptying.

• Radiation Oncology Journal
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• 제17권2호
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• pp.141-145
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• 1999

목적: 방사선 치료시 유발되는 오심과 구토에 대하여 5-hydroxytriptamine 길항제인 그라니세트론을 투여하여 그 효과에 대한 임상적 효능과 방법, 사용기간, 부작용 등에 대한 기본적인 자료를 얻고자 본 연구를 시행하였다. 대상 및 방법 : 병리학적으로 암으로 확진된 18세 이상의 성인 남녀 10명(직장암 4명, 자궁경부암 2명, 자궁내막암 1명, 정상피종 1명, 폐암 1명, 백혈병 1명)을 대상으로 그라니세트론 치료의 효과를 조사하였다. 그라니세트론은 경구 투여로 2mg을 하루 1회 사용하였으며, 방사선치료 후 오심이나 구토 증상이 나타나기 시작하면 사용하여 2주간 계속적으로 투여하였다 환자의 오심의 정도, 구토 회수, 부작용 등의 증세는 방사선치료 시작일로부터 하루 한번씩 기록하여 24시간 후와 제7일 째의 결과를 분석하였다. 오심은 무증상, 경증, 증등도, 중증 등 4단계로 분류하였으며 무증상과 경증을 치료효과가 있는 것으로 판정하였다. 구토 억제에 대한 효과는 완전효과, 주효효과, 경미효과, 치료실패 등으로 구분하였고 완전효과와 주효효과를 구토가 조절된 것으로 정의하였다. 결과 : 오심에 대한 효과는 그라니세트론 투여후 제7일에 전체 10명중 9명(90$\%$)에서 증삶이 호전되었다(무증상=6명, 경증=3명). 구토증세에 대한 조절효과는 제7일에 완전효과가 70$\%$ 주효효과가 30$\%$,로 전체적인 치료효과는 100$\%$에서 구토가 조절되었으며 경미효과나 치료실패로 판정된 환자는 없었다. 부작용으로는 경도의 두통을 호소한 환자가 1명 있었고 또 다른 1명에서 경도의 어지러움증을 호소하였으나 특별한 치료없이 곧 소실되었고, 변비나 추체외로 증상은 한 예도 없었다. 결론 : 대부분의 환자(100$\%$)에서 일주일간의 그라니세트론 투여로 오심(90$\%$) 및 구토(100$\%$)의 증상을 억제할 수 있었으나 항암제와 방사선요법을 병행하는 환자나 넓은 부위를 치료하는 경우는 방사선 치료가 끝날 때까지 계속적으로 그라니세트론을 투여할 필요가 있었다. 항암제 투여시 동반되는 오심과 구토는 주요 관심의 대상으로 이에 대한 치료 방법과 효과에 대해서는 비교적 많은 연구가 이루어져 있으나, 방사선치료 시에 나타나는 이러한 증상에 관한 연구는 미흡한 실정이며 효율적인 방사선치료를 위해서는 앞으로 항구토제의 투여 방법 및 기간 등에 관한 체계적인 연구가 필요하다고 하겠다.