• Bulletin of the Korean Chemical Society
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• 제31권1호
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• pp.52-58
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• 2010

Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.

• 한국식품저장유통학회지
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• 제24권5호
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• pp.593-599
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• 2017

본 연구는 불고기에 SHS와 HPP 기술을 적용하여 냉장온도(5, $10^{\circ}C$)에서 저장하면서 그 품질변화를 살펴보았다. SHS 조리가 일반조리에 비해 다즙성과 조직감(연한 정도)가 향상되는 것을 알 수 있었다. 이것은 조직감 측정결과와 같은 경향으로 SHS 조리가 일반조리에 비해 조직이 연해져 부드러운 조직감을 부여하는 것을 알 수 있었다. 또한 총균수의 증가폭도 일반 조리구에 비해 적은 것을 확인할 수 있었으며 지방 산패도 값인 TBA 또한 SHS-HHP병행 처리군이 일반 조리에 비해 낮은 값을 보여 안전성을 확보할 수 있을 것으로 사료되었다. 식육의 신선도를 나타내는 VBN 은 간장 양념으로 인해 높은 값을 보여 본 연구의 특성상 VBN 함량만으로 신선도 정도를 판단하기는 어려울 것으로 사료된다. 이상의 결과로 기존의 불고기 제품에 SHS 기술과 HPP 기술의 적용으로 제품의 품질향상을 통한 조직감 상승과 유통기간 연장효과를 어느 정도 기대할 수 있는 것으로 생각되었다.

• 대한한의학회지
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• 제19권2호
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• pp.373-390
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• 1998

35 theses conducted in Korea on the topic of senescence or anti-oxidant were classified on the basis of research methods, animals used for the experiments, and research items. Evaluating these research works with respect to the Free Radical Theory, the following conclusions were reached. 1. Of the 17 theses written in the Oriental medicine aspect, three theses used a single herb, nine theses used a complex prescription, four theses concentrated on the usage of the medicinal acupuncture, and one research paper focused on using scientific components. Common objection of these papers were on the verification of the efficacy of herbs. 2. Of the 18 these written in the Western medicine aspect, five theses used a single drug, seven theses conducted a research on the changes due to senescence, and 6 papers were on variety of topics. The main focus of these works were on the mechanism and pathology related to the senescence rather than on the suppression of senescence. 3. Among the theses written in the Oriental medicine perspective, a total of 48 herbs were utilized. 26 of these herbs has a tonification function on the Kidney. Six out of nine complex prescription mentioned above has a function of tonifying the Kidney. 4. With respect to the research subjects used on the experiments, 8 theses have used Senescence-Accelerated mice, 13 theses have used Sprague-Dawley mice, and remaining 7 papers have used human or other animals. 5. These are the categorization of the research items used: the weight (11) and weight changes of the visceral organs (9), the measurement of the content of peroxide-disease (9), the measurement of enzyme vitality (21), the blood and urine test (10), the experiment concerning immune system (3), the influence on the hepatic capability of metabolizing foreign substance (3), the effect on hepatic cell protection (3), the measurement of both the suppression of Free Radical and ability to create Free Radical (2), the measurement of effect of suppresing MDA(malondialdehyde) (4), the effect of eliminating DPPH Radical (2), and experiements about the functions (2). 6. The rate of vitalization of well known anti-oxidants such as Superoxide dismutase (SOD), Protein-bound SH, Nonprotein-bound SH, Glutathione(GSH), Catalase, and etc. were tested in 17 theses. Considering the conclusions mentioned above, the theses related to the senescence published in Korea elected different animals used for experiments, research items and the methods of research, the end result seems to be a lack of objectivity. Thus, I would argue that research methods to overcome such a deficiency need to be developed systematically.

• 대한한의학회지
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• 제30권1호
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.866-873
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• 2006

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

• 한국응용곤충학회지
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• 제59권2호
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• pp.133-138
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• 2020

2016년에 쌍별귀뚜라미는 식품의약품안전처 식품공전에 등록된 식품원료로 가장 큰 장점은 월동 없이 연중 대량 사육이 가능하다는 것과 60% 이상의 단백질 함량이다. 본 연구에서는 사육공간, 인건비 등의 문제로 인하여 귀뚜라미 사육이 불가능할 때를 대비하여 저장조건을 설정하였으며, 산란율이 높은 산란처 선발과 알의 동종포식률을 조사하였다. 산란은 상토 산란처에서 가장 선호도가 높았으며(p < 0.05), 알의 동종포식률을 보았을 때 10 L 당 종령 약충 62마리 이하, 1일 동안 산란을 받는 것이 가장 적합한 것으로 판단되었다(p < 0.05). 알의 저온 저장을 하였을 때는 28℃에서 10일간 보관 후 16℃에서 10일간 저온 저장했을 때 부화율이 가장 높았고, 저장을 하지 않았을 때와 비교하였을 때 12~14일 부화를 연장할 수 있었다(p < 0.05). 쌍별귀뚜라미의 산란처, 산란 방법 및 알 저장조건을 설정함으로써 효율적인 생산방법을 제시하였다.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Animal cells and systems
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• 제14권4호
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• pp.275-282
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• 2010

Chunghyul-dan (CHD) is a combinatorial drug known to exert anti-inflammatory effects in endothelial cells. In this study, we employed global transcriptional profiling using cDNA microarrays to identify molecular mechanisms responsible for the anti-inflammatory activity of CHD in endothelial cells. An analysis of the microarray data revealed that transcript levels of monocyte chemotactic protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1) and activated leukocyte cell-adhesion molecule were dramatically altered in CHD-treated endothelial cells. These changes in gene expression were confirmed by RT-PCR, Western blotting and ELISA. Chronic CHD treatment also appeared to decrease MCP-1 secretion, probably as a result of decreased MCP-1 expression. In addition, we determined that chronic CHD treatment inhibited lipopolysaccharide-stimulated adhesion of THP-1 leukocytes to endothelial cells. The inhibitory effect of CHD on LPS-stimulated adhesion resulted from downregulation of VCAM-1 expression. Transmigration of THP-1 leukocytes through endothelial cells was also inhibited by chronic CHD treatment. In conclusion, CHD controls a variety of inflammatory activities by regulating MCP-1 and VCAM-1 gene expression.

• 한국식품저장유통학회지
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• 제14권4호
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• pp.337-344
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• 2007

표고버섯 분말을 첨가한 전병을 제조하여 첨가 수준별 품질특성을 조사하였다. 전병 반죽의 물성 특성 중 흡수율은 표고버섯 분말 첨가량이 많아지면서 증가하였으며, 반죽도달시간과 최고점도는 첨가량에 따라 낮아졌다. 또한 extensogram을 통한 반죽의 energy값은 첨가량과 부의 결과를 보였으며 신장도도 감소하였다. 표고버섯 분말 첨가 전병의 일반성분은 대조구에 비해 수분, 조단백질과 회분의 경우 증가하였고, 탄수화물 함량은 감소하였으며 20% 첨가구의 경우 약간 눅눅한 상태로 전병이 제조되어 전병 제조 시 표고버섯 분말 첨가량은 20%를 넘지 않는 것이 적당할 것으로 판단된다. 색도를 분석한 결과 L값과 b값은 첨가량이 증가하면서 유의적으로 감소하였고, a값은 10% 이상 첨가구에서 다소 증가하는 결과를 보였다. 또한 10% 이상 첨가시 기존 대조구와 현저한 색의 차이를 보이는 것으로 나타났다. Rheometer를 이용한 물성 측정 결과 경도(hardness)는 15%까지 증가하다 20% 첨가구에서 크게 감소하였는데, 이는 20% 시료의 조직이 눅눅한 상태의 결과와 일치하였다. 최대 하중값과 파단점도 경도와 비슷한 결과를 보여 대조구에 비해 증가하였다. 시료별 관능검사 결과는 색(color), 향(flavor), 맛(taste)과 전반적인 기호도(overall acceptability) 등 모든 항목에서 10% 첨가구가 가장 높은 점수를 받았으며 15% 이상 첨가 할 때 기호도가 조금씩 감소하는 것으로 나타나 전병 제조 할 때 최적의 표고버섯 분말 첨가량은 10% 수준이 될 것으로 판단된다.

• 대한본초학회지
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• 제23권3호
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• pp.127-134
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• 2008

Objectives : The present study was designed to investigate whether Ostericum koreanum (OK) could regulate lipopolysaccharide (LPS)-induced inflammatory response in vitro and in vivo. Methods : To evaluate of anti-inflammatory effect of OK, we examined Nitric oxide (NO), proinflammatory cytokines production in LPS-stimulated RAW264.7 cells. Furthermore, we checked molecular mechanism especially in the phosphorylation of mitogen-activated protein kinases (MAPKs) and the degradation of inhibitory kappa B a ($Ik-B{\alpha}$) using western blot and also investigated survival of mice in LPS-mediated endotoxin shock. Results : 1. Extract from OK itself have weak cytotoxic effect on RAW264.7 cells. Extract from OK inhibited LPS-induced NO, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, IL-6 and IL-10 production in RAW264.7 cells. 2. OK inhibited the phosphorylation of MAPKs, such as p38, extracelluar signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) and also the degradation of $I{\kappa}-B{\alpha}$ in the LPS-stimulated RAW264.7 cells 3. OK did not inhibit LPS-induced endotoxin shock. Conclusions : OK down-regulated LPS-induced NO and cytokines production through suppressing activation of MAPKs and degradation of $I{\kappa}-B{\alpha}$. Our results suggested that OK may be a beneficial drug against inflammatory diseases.