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천연물에서 단리한 식물정제 탄닌의 항암효과 및 생물학적 반응 조절 물질로서의 기능 검색
이도익,조장현,이민원,Lee, Do-Ik,Cho, Jang-Hyun,Lee, Min-Won 대한약학회 1998 약학회지 Vol.42 No.4
Praecoxin A, an ellagitannin, purified from Alnus hirsuta var.microphlla was evaluated on the antitumor activity. Praecoxin A had the significant cytotoxicity to s ix tumor cell lines: human chronic myelogenous leukemia K-562, human promyelocytic leukemia HL-60, mouse leukemia P388, mouse lymphocytic leukemia L-1210, sarcoma-l8O, mouse lymphoma L5178Y except L-1210. And the most sensitive cell line was K-562 ($ED_{50}=2.43{\mu}g/ml$). The $ED_{50} of praecoxin A against HL-60, P388, L-1210, sarcoma7l8O and L5178Y were 6.28, 8.66, 10.00, 7.01, $9.32{\mu}g/ml$, respectively. Praecoxin A showed the increasing effect in life span by 36.8% on the 1st day after treatment of 10mg/kg in mice bearing sarcoma-180 tumor cells (ascitic form) via NCI (National Cancer Institute, U.S.A.) protocol in vivo assay. As a result, praecoxin A is considered to show the antitumor activity.
Pedunculagin의 Macrophage에 대한 항암활성 및 Nitric Oxide 생성
이도익(Do Ik Lee),김형근(Hyung Keun Kim),이민원(Min Won Lee),최영욱(Young Wook Choi),김하형(Ha Hyung Kim),김은주(Eun Joo Kim) 대한약학회 2000 약학회지 Vol.44 No.2
Pedunculagin is an ellagitannin purified from Alnus hirsuta var. microphylla, Betulaceae. The effects of pedunculagin on the immune system have been characterized to induce enhancement of NK (natural killer) cell cytotoxicities against tumor cells. The present study investigated whether pedunculagin can enhance macrophage cytotoxicity against P815 tumor cells. Macrophage cultured with pedunculagin enhanced cytotoxicity in a dose dependent manner. In addition, the same treatments increased NO production, which plays important roles in the immune system. Taken together, these results demonstrate that pedunculagin significantly enhances cytolytic activities of macrophage.
Pedunculagin의 NK cell에 대한 활성화와 흑색종의 전이 억제 효과
이도익(Do Ik Lee),김형근(Hyung Keun Kim),이민원(Min Won Lee),최영욱(Young Wook Choi),김하형(Ha Hyung Kim),김은주(Eun Joo Kim) 대한약학회 2000 약학회지 Vol.44 No.2
Pedunculagin is an ellagitannin purified from Alnus hirsuta var. microphylla, Betulaceae. The effects of pedunculagin on immune system have been characterized to induce enhancement of NK (natural killer) cell cytotoxicities against tumor cells. Here, we report the evaluation of the effects of pedunculagin on the growth of murine B16-FlO melanoma in vivo. After the intradermal inoculation of B16-FlO melanoma, B16-FlO tumors grew progressively in immunocompetent syngenic C57BL/6 mice. The mice treated with pedunculagin(10mg/kg, every 48hrs) resulted in a significant improvement in survival. Inhibitory effects of pedunculagin on lung metastasis in C57BL/6 mice were also detected. Summarizing treatment with pedunculagin has a significant antitumor effect upon B16-FlO murine melanoma.
오리나무유래 디아릴헵타노이드 허수테논의 T 세포활성억제 및 항아토피 효능연구
이도익(Do Ik Lee),서성준(Seong Jun Seo),주성수(Seong Soo Joo) 한국식품과학회 2013 한국식품과학회지 Vol.45 No.4
본 연구에서는 오리나무유래 HST의 T 세포 비활성화 효능을 확인하고 그 기전을 탐색하여 새로운 항아토피 천연소재로의 개발 가능성을 제시하고자 하였다. HST는 T 세포 mitogen으로서 anti-CD3 mAb가 처리 된 마우스 비장에서 Th 사이토카인(IL-2, IFN-γ, IL-4, IL-5, IL-10)의 발현을 효과적으로 억제하였으며, T 세포 early activation marker인 CD25 유전자 발현이 INCA-6에서 매우 효과적으로 억제되는 것으로 보아, NFAT inactivator-유사 NFAT 탈인산화 억제 기전을 가지는 것으로 예측되었다. 또한 세포주기조절 단백질인 p21과 p27의 유전자도 HST에 의해 upregulation이 되어 효과적인 T 세포 증식 및 분화를 억제할 것으로 생각되었다. 이러한 세포주기조절 효과는 AD를 악화시키는 세균인 S. aureus 성장억제 실험에서 확인되어 향후 항박테리아 효능을 갖는 우수한 항아토피피부염 천연소재로서 HST의 활용 가치가 높을 것으로 판단된다. Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However, it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model. Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation, similar to INCA-6.
인삼 사포닌과 다당류 혼합물의 활성화된 RAW264.7 세포주에 대한 염증조절 효과
이도익(Lee Do Ik) 대한약학회 2010 약학회지 Vol.54 No.2
It is well known that the numbers and functions of immune-associated cells are increased by saponins and polysaccharides in ginseng. In this study, the mixture of polysaccharide and saponin (MPS) from Panax ginseng is applied to LPS- activated RAW 264.7 cells. The production of NO and the gene expression of IL-6 and TNF-α are decreased in LPS-activated RAW 264.7 cells and the expression of arginase II and PD-1L genes is decreased in LPS-untreated macrophages. Therefore, the mixture of saponin and polysaccharide from Panax ginseng could be used in order to regulate immune responses.
입체구조적으로 안정화된 리포좀의 특성 및 혈장내 안정성
이지혜(Ji Hye Lee),이상길(Sang Kil Lee),전호성(Ho Seong Jeon),김하형(Ha Hyung Kim),이도익(Do Ik Lee),이민원(Min Won Lee),최영욱(Young Wook Choi) 대한약학회 2000 약학회지 Vol.44 No.3
Sterically stabilized liposomes (SSL) composed of distearoylphosphatidylcholine, cholesterol, dicetylphosphate and distearoylphosphatidylethanolamine-N-poly (ethyleneglycol) 2000 (DSPE-PEG 2000) were made by reverse phase evaporation method to prolong biological half-life and decrease toxic side effect of drug. Streptozocin (STZ), a water-soluble antitumor agent with short half-life, was selected as a model drug. The size of SSL was controlled by polycarbonate extrusion to 100nm which is adequate size for long circulation in plasma. The release rate of drugs from SSL in PBS was evaluated. And the stability of STZ-containing liposomes against drug leakage into rat plasma was evaluated in order to investigate the interaction of liposome and plasma protein. Incorporation of DSPE-PEG 2000 into conventional liposomes significantly decreased the drug leakage into rat plasma.
흰쥐에서 ${\alpha}$-Adrenaline 效能 藥物등이 피마자油 誘發泄瀉에 미치는 영향
허인회,이도익,이종흔,김동휘,Huh, In-Hoi,Lee, Do-Ik,Lee, Jong-Heun,Kim, Dong-Whee 대한약학회 1984 약학회지 Vol.28 No.4
The effect of lofexidine, clonidine, and other drugs on castor oilinduced diarrhea in rats was investigated. Castor oil was administered orally and drugs were administered intraperitoneally. The results were as follows. 1. Lofexidine(0.1-43{\mu}mol$/kg) blocked dose dependently caster oil-induced diarrhea like clonidine, but its potency was weaker than that of clonidine, 1. Yohimbine (1-10{\mu}mol/kg$) antagonized the antidiarrheal action of lofexidine and clonidine. 3. Prazosin (3-30{\mu}mol/kg$) did not antagonize the antidiarrheal action of lofexidine and clonidine. 4. Metoclopramide, bromocriptine mesylate, and nadolol did not affect antidiarrheal action of lofexidine significantly. 5. Loperamid prolonged the antidiarrheal action of lofexidine.
흰쥐 뇌 소교세포에서 진세노사이드 Rg3의 Type A Macrophage Scavenger Receptor 발현 증진효과
주성수,황광우,이도익,Joo, Seong-Soo,Hwang, Kwang-Woo,Lee, Do-Ik 대한약학회 2005 약학회지 Vol.49 No.2
Macrophage scavenger receptors (MSRs) induce microglial interaction with ${\beta}$-amyloid fibrils (fA${\beta}$) that are associated with Alzheimer's disease (AD). Although microglia are know n to have a dual effect on formation of plaque and clearance of fA${\beta}$ in the AD brain, receptor-mediated phagocytosis is a very important tool for preventing amyloid plaque via activated microglia in the early stage of AD. In the study, we examined whether ginsonoside Rg3 enhances the microglial Phagocytosis of A${\beta}$1-42 through Phagocytosis assay, gene expression (RT-PCR) and protein assay (western blots) for the cell responsiveness presented between Rg3-treated and non-treated groups. Fluro-labeled Ac-LDL and E.coli particles were used as control proteins for phagocytosis. In previous studies, this was a particularly interesting property of Rg3 in the stimulation and phagocytosis of macrophages in the periphery. We report here that ginsenoside Rg3 increased the expression of type-A MSR (MSR-A) in microglia and thus accelerated the phagocytosis with an effective degradation of engulfed fA${\beta}$. This result suggests that Rg3 may play an important role in removing fA${\beta}$ by enhancing the receptor-mediated phagocytosis. In addition, Rg3 could be a potential candidate for balancing the rate of production of fA${\beta}$ in AD brain.
천연 퀘루세틴이 수종 항생물질의 항균력에 미치는 병용효과
어성국,김영소,이종길,이도익,김일혁,한성순,Eo, Seong-Kug,Kim, Young-So,Lee, Chong-Kil,Lee, Do-Ik,Kim, Il-Hyuk,Han, Seong-Sun 대한약학회 1996 약학회지 Vol.40 No.6
As part of our search for less toxic antimicrobial agents from natural resources. rutin was isolated from Sophora japonica and then hydrolyzed to quercetin. Antimicrobial activity of quercetin was tested in vitro against five kinds of gram positive and ten kinds of gram negative bacteria by serial broth dilution method. Among fifteen kinds of bacteria tested, the antimicrobial activity of quercetin was the most potent against Proteus vulgaris showing minimal inhibitory concentration(MIC) of 125 ${\mu}$g/ml. To investigate the effect of antimicrobial combinations of quercetin with four kinds of antibiotics (ampicillin, cefazolin, oxytetracycline and chloramphenicol). the fractional inhibitory concentration index (FICI) was determined by checkerboard assay for each strain. The antimicrobial combinations of quercetin with four kinds of antibiotics resulted in synergism in one instance, additive effect in four instances, but no antagonism was observed.
간암세포주 HepG2 2.2.15에서 아만타딘/비페닐디메칠디카르복실레이트 복합제의 항 바이러스 효과
주성수,원태준,이용진,황광우,이도익,Joo, Seong-Soo,Won, Tae-Joon,Lee, Yong-Jin,Hwang, Kwang-Woo,Lee, Do-Ik 대한약학회 2005 약학회지 Vol.49 No.2
For decades, the demand for new antiviral strategies, especially in hepatitis, has increased markedly due to its devastating pathogenic outcome, In the present study, we examin ed the antiviral effect of the combination of amantadine and biphenyl dimethyl dicarboxylate (DDB) in HepG2 2.2.15, which is transfected with HBV DNA. The study demonstrated that the combination not the single treatment may have an anti-HBV effect through a synergism of antiviral, anti-inflammatory and cytoprotective activities in STAT1 ${\alpha}$, 6-16 gene, and pro-inflammatory components such as nitric oxide and IL-1${\beta}$ expression. In addition, hepatitis B surface and core gene expression were examined as a final end point for the anti-HBV activities, which was also significantly suppressed comparing to normal control (p<0.01).