• Archives of Pharmacal Research
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• 제19권5호
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• pp.390-395
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• 1996

To investigate whether $AT_{1}$ receptor antagonists are acting by increasing endothelium-de-pendent and -independent relaxation of aortas in normotensive rats, $AT_{1}$ receptor antagonists, losartan and KR-30988, and angiotensin converting enzyme inhibitor, captopril, were orally administered for two weeks (50 mg/kg, b.i.d.). THe blood pressure, heart rate and body weight were not significantly changed by losartan, KR-30988 and captopril compared to the control group. In aortic preparations, the $pD_{2}$ of KR-30988 for ACh-induced relaxation was 8.33 $\pm$ 0.16, significantly (p <0.05) lower than that of control group $(7.71 \pm 0.15)$. ACh-induced relaxation was significantly increased on losartan-treated group (p<0.01) at $10^{-6}$ M of ACh, and in captopril-treated group (p<0.05) at the range of $10^{-7}$ -$10^{-5}$ M of ACh. The $pD_{2}$ values for histamine-induced relaxatio of losartan, KR-30988 and captopril were 5.57 $\pm$ 0.10, 5.85 $\pm$ 0.21 and 5.60 $\pm$ 0.01, respectively, with significant differences in all groups (p<0.01) compared to that of control group (5.13 $\pm$ 0.09). ACh-induced relaxations of aortic preparations were not changed by pretreatment of indomethacin ($10_{-5}$ M), and completely bolcked by pretreatment of L-NAME $(10_{-5}M)$ in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that $AT_{1}$ receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxatio on aortic preparations through the release of, or increase sensitivity, to nitric oxide in nor-motensive rats.

• 약학회지
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• 제43권5호
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• pp.642-651
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• 1999

Nonsedating antihistamines do net cause sedation in therapeutic doses because these drugs hardly cross the blood-brain barrier. Since most of the peripheral side dffects of conventional antihistamines are related to their muscarinic receptor blocking action, the present study was performed to investigate whether nonsedating antihistamines interact with the muscarinic receptors and discriminate the muscarinic receptor subtypes in the rat cerebral microsomal fraction which containes both $M_1,{\;}M_2,{\;}M_3{\;}and{\;}M_4$ receptors. Five nonsedating antihistamines at high concentrations inhibited [$^3H$]QNB binding to the muscarinic receptor in a dose-dependent manner. The inhibition curves of these drugs except loratadine which showed positive cooperativity (nH=1.55) were steep (nH=1), indicating interaction with a single homogenous population of the binding sites. Astemizole, clemizole and mequitazine increased the $K_D$ value for [$^3H$]QNB without affecting the binding site concentrations, and this increase in the $K_D$ value resulted from the ability of these drugs to slow [$^3H$]QNB-receptor association. The Ki values of astemizole, clemizole and mequitazine for the inhibition for the inhibition of [$^3H$]QNB binding to muscarinic receptor were 0.58, 5.99 and $0.007{\;}{\mu}M$, respectively. However, loratadine and terfenadine inhibited noncompetitively [$^3H$]QNB binding with the normalized $IC_50$ value of about $2{\;}{\mu}M$. These results demonstrate that; 1) astemizole, clemizole and mequitazine interact directly with the muscarinic receptor at high concentrations; 2) muscarinic receptor blocking potency of these drugs varies widely among drugs; 3) these drugs do not discriminate between muscarinic receptor subtypes.

• 동의생리병리학회지
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• 제34권5호
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• pp.245-254
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• 2020

The purpose of this study was to investigate the effects of natural herb mixture containing Laminaria japonica Areschoung (LAM) on fine dust-induced bronchitis in mice. Laminaria japonica Areschoung is main content of LAM, which is including fucoidan. Fucoidan extracted from phaophyta is known to prevent bronchitis and to defend against bacteria and virus infection. In this study, we experienced the effect of LAM on bronchitis and investigated gene expressions (e.g ; IL-8, COX-2, MCP-1) and bio-markers (e.g ; IL-8, PGE2, MUC5AC) associated with bronchitis by using A549 cells. Also, we investigated whether LAM can suppress the bronchitis in fine dust-induced animal models. We injected fine dust (50 ㎕) twice as INT (Intra-Nasal-Trachea) method. Then LAM (200 mg/kg and 400 mg/kg) were oral administered for 14 days. We analyzed the number of immune cells, immunoglobulin E, bio-markers level associated with bronchitis. LAM significantly decreased bio-marker (IL-1β, IL-6, IL-8, TNF-α, Histamine, PGE2), immune cells (white blood cell, neutrophil, lymphocyte, monocyte), and immunoglobulin E, that are increased by fine dust. Taken together, this study suggest that LAM can be used as effective herbal extract for bronchitis.

• 식품산업과 영양
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• 제9권1호
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• pp.36-45
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• 2004

Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.

• 동의생리병리학회지
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• 제36권5호
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• pp.187-192
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• 2022

The purpose of this study is to examine the effect of herbal medicine complex (HMC) containing Camellia sinensis L., Duchoesna chrysantha, Houttuynia cordata Thunberg, Poncirus trifoliata Rafinesque on skin inflammation and atopic dermatitis. First, we examined the anti-inflammatory effect of HMC in TNF-α induced human keratinocytes (HaCaT cell). Real-time PCR and western blotting were performed to evaluate the expression of inflammatory cytokines (e.g., iNOS, COX-2, IL-6, IL-8) mRNA and protein. Four-weeks old male NC/Nga mice were treated with 1% 2,4-dinitrochlorobenzene (DNCB) solution and used as an atopic dermatitis mice model. And, HMC (200 mg/kg or 400 mg/kg) was administered directly into the stomach of mice for 4 weeks, and blood or serum analysis, tissue staining were performed after oral gavage. As a result HMC inhibited the mRNA expression of iNOS, COX-2, IL-6, and IL-8, which had been increased by TNF-α in HaCaT cells. In addition, the protein expression was also significantly suppressed in the same way as the mRNA expression results. The in vivo experiment results showed that, HMC administration reduced thickening of the epidermis and infiltration of eosinophil into the skin stratum basale compared to DNCB treatment. In addition, HMC administration significantly reduced the inflammatory cytokines (IL-4, IL-5, IL-6, and IL-13) production and immunocyte (white blood cell, lymphocyte, neutrophil, and eosinophil) count compared to DNCB treatment. Moreover, the serum IgE and histamine level was decreased by HMC administration. These results suggest that HMC can be used as effective herbal medicine extract for skin inflammation and atopic dermatitis. And this study may contribute to the development of the herbal medicine-based drug for the treatment of skin inflammation and atopic dermatitis.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.723-735
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• 1998

배 경: 비타민 C가 동물실험에서 기도 과민성을 감소시키는 역할을 하는 것으로 보고되고 있는데 이는 비타민 C가 히스타민 분해를 촉진하고, cyclooxygenase 통로를 $PGF_{2\alpha}$에서 $PGE_2$로 이동시키며 평활근 수축을 감소시키고, 산화물의 환원제로 작용하는 사실에 기인한다고 한다. 또한 비흡연자에 비하여 흡연자에서 혈중 비타민 C 농도가 감소하는데 이는 비타민 C가 흡연시 생성되는 산화물의 환원제로 소모되며, 니코틴에 의해 분비되는 catecholamine, serotonin의 합성에 관여하며, 결핍된 식이로 인한 것으로 알려져있다. 연구자들은 기도 과민성이 있는 흡연자와 대조군인 비흡연지를 대상으로 비타민 C의 기도 과민반응에 대한 효과를 알아보고 비타민 C의 기도 과민성에 대한 역할을 알아보고자 본 연구를 시행하였다. 방 법: 17명의 흡연자와 8명의 비흡연자에서 기도 과민반응에 대한 비타민 C의 급성 효과를 알아보기 위하여 혈중 비타민 C 농도 측정을 위한 채혈과 폐기능 검사와 메타콜린 기관지 유발검사를 시행하고 비타민 C 3 g 투여 후 1시간 뒤에 상기 검사들을 다시 시행하였고 1주 후 기도 과민반응에 대한 비타민 C의 만성 효과를 알아보기 위하여 17명의 흡연자에서 1주 동안 매일 비타민 1 g 투여 후 혈중 비타민 C 농도 측정을 위한 채혈과 폐기능 검사와 메타콜린 기관지 유발검사를 시행하였다. 또한 기도 과민성에 대한 비타민 C 의 역할을 알아보기 위하여 l주 후 메타콜린에 반응하는 15명중 12명의 흡연자에서 비타민 C 3 g과 cyclooxygenase 억제제인 indomethacin 100 mg을 동시 투여 후 폐기능 검사와 메타콜린 기관지 유발검사를, 1 주 후 메타콜린에 반응하는 12명의 흡연자에서 indomethacin 100 mg만 단독 투여 후 폐기능 검사와 메타콜린 기관지 유발 검사를 시행하였다. 결 과: 전혈 비타민 C 농도를 측정한 결과 흡연자, 비흡연자 각각 $1.17{\pm}:0.22$ mg/dL, $1.14{\pm}:0.19$ mg/dL로 유의한 차이는 없었다(p>0.05). 흡연자 17명중 15명(88.2%)이 메타콜린 기관지 유발검사 양성이었고 이중 10명은 $PC_{20}FEV_1$이 8mg/mL 이하였고, 비흡연자군 8명중 7명(87.5%)이 기관지 유발검사 음성이었다. 기관지 유발집사 양성인 15명의 흡연자중 13명에서 비타민 C 3 g 복용 1 시간 후 기관지 반응이 유의하게 감소하였고 l일 비타민 C 1 g 씩 1 주간 복용 후에도 기관지 반응의 감소가 계속 유지되었다. 흡연자의 $PC_{20}FEV_1$과 전혈 비타민 C 농도 사이에는 유의한 상관관계는 없었다. 비타민 C 3 g 투여 후 흡연자에서 관찰할 수 있었던 기관지 반응의 유의한 감소가 indomethacin 100 mg 첨가 후 소실되었다(p>0.05). 결 론: 이상의 결과로 볼 때 혈중 비타민 C 농도는 흡연자군, 비흡연자군에 있어서 유의한 차이가 없지만 흡연자군은 비흡연자군에 비하여 기도 과민성이 유의하게 증가되어 있었으며, 비타민 C 투여에 의해 증가된 기도 과민성이 유의하게 감소하고 indomethacin 첨가 후 비타민 C의 이러한 효과가 소실됨으로 보아 비타민 C가 arachidonic acid 대사작용에 관여함으로 기도 과민성이 감소되리라 사료된다.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.405-411
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• 2006

Epinastine is an antiallergic drug effective for bronchial asthma, allergic rhinitis, urticaria and dermatitis. Epinastine is topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. The purpose of the present study was to evaluate the bioequivalence of two epinastine hydrochloride tablets, Alesion Tablet (Boehringer Ingelheim Korea Ltd.) and S-napine tablet 10 mg(Sam Chun Dang Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration(KFDA). The release of epinastine from the two epinastine formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media(pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.35{\pm}1.57$ years in age and $66.29{\pm}10.61kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 20 mg as epinastine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of epinastine in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the 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 using logarithmically transformed $AUC_t.\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Alesion tablet, were 1.50, 1.46 and -13.48% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25(e.g., log 0.95$\sim$log 1.12 and log 0.93$\sim$log 1.10 for $AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating S-napine tablet 10 mg was bioequivalent to Alesion tablet.

• 대한한방소아과학회지
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• 제25권1호
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• pp.1-27
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• 2011

Objectives: The purpose of this study is to investigate the effects of Yijungtang(YJT) on atopic dermatitis in an in-vitro and in-vivo experiment using a RBL-2H3 mast cells and a NC/Nga atopic dermatitis mouse. Methods: In-vitro experiment, IL-4, IL-13 mRNA expression were evaluated by a real-time PCR, IL-4, IL-13 production by ELISA and transcription factor as GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-kB by western blotting. In-vivo experiment, clinical skin score we evaluated by, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, cytokine level, total number of cell, Immunohistochemical staining and Histological features of auxiliary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results: YJT decreased IL-4, IL-13 mRNA expression, IL-4, IL-13 production and prominently decreased the expression of mast cell specific transcription factors including GATA-2, NF-AT2, c-Fos and NF-kB. YJT oral administration reduced the levels of skin severity scores. It also decreased the level of inflammatory cytokines such as IL-5, IL-13, histamine and IgE in the serum. It elevated IFN-gamma level in the spleenocyte culture supernatant but decreased. $CD3e^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $CD11b^+Gr-1^+$, $CCR3^+$ in the PBMCs, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $B220^+CD23^+$ in the ALN, $CD4^+$, $CD3e^+CD69^+$ in the ALN and $CD4^+$, $CD11b^+Gr-1^+$ in the dorsal skin. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by YJT oral administration. Conclusions: The anti-allergic activities of YJT may be mediated by down-regulation of Th2 cytokines, such as IL-4 and IL-13, through the regulation GATA-2, NF-AT2 and NF-kB transcription factors in mast cells. YJT would be regulate molecular mediators and immune cells which are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.106-106
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• 1995

A polysaccharide, G009, isolated from Ganoderma lucidum IY009 subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000mg/kg in mice did neither exhibit any abnormal behaviors nor effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guinea-pig ileum and trachea, it did not show any contraction or relaxation at the concentration of 2$\times$10$^{-3}$g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine did not inhibited by the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000mg/kg in rats.

• The Korean Journal of Physiology
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• 제11권1호
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• pp.27-32
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• 1977

Diospyros Kaki Thunberg is the species of persimmon tree that grows in Korea. Although its fresh or dried fruits are often served as a desert, it has little been known if persimmon tree has any specific pharmacological action. The leaves and branches of persimmon tree has long been used as folk remedies for palsy and frostbite in the southern part of Korea and it is also in use for the treatment of hiccup and nocturnal enuresis in chinese herbal medicine. Recently it was reported that an intravenous administration of Diospyros Kaki Thunberg ethanol extract (KTEE) into the animals lowered arterial blood pressure. Lee concluded from his study on the mechanism of depressor action of KTEE that at least a part of depressor response he observed was caused by acetylcholine-like action of KTEE. On the other hand little study has been made on the effect of KTEE on the motility of isolated animal intestines. Therefore the present study was undertaken to investigate effect of KTEE and the mechanism of its action on the motility of isolated rabbit duodenum. Ethanol extract of Diospyros Kaki Thunberg was prepared by boiling 1 kg of dried branches of persimmon tree in 1 liter of ethanol and the motility of isolated rabbit duodenum was recorded on physiograph by means of force transducer connected with Magnus apparatus. Doses of KTEE used were $5{\times}10^{-4}gm/ml,\;1{\times}10^{-3}gm/ml,\;and\;2{\times}10^{-3}gm/ml$. And the isolated duodenum was separately pretreated with acetylcholine $(5{\times}10^{-7}gm/ml)$, pilocarpine $(2.5{\times}10^{-6}gm/ml)$, histamine $(5{\times}10^{-6}gm/ml)$ and barium chloride $(2.5{\times}10^{-5}gm/ml)$ in order to find out interactions of these drugs with KTEE. The results obtained are as follows: 1. At doses of $5{\times}10^{-4}gm/ml,\;1{\times}10^{-3}gm/ml$ KTEE reduced contractions of isolated duodenum, while tonus as well as contaction of duodenum were depressed with $2{\times}10^{-3}gm/ml$ of KTEE. 2. Since the inhibitory effect of KTEE on the intestinal motility was not blocked by pretreatment with acetylcholine, pilocarpine, and barium chloride, it was strongly suggested that the inhibitory action of KTEE on intestinal motility is mainly Caused by its antihistamine effect. 3. It is also concluded that the principal substance of KTEE responsible for inhibition of intestinal motility may also have a vasodilating activity and would not be an acetylcholine-like substance in case it is same substance as that cause depressor responses.