• Applied Biological Chemistry
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• 제41권6호
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• pp.477-482
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• 1998

새로운 Leukotriene $D_4$ antagonists를 찾기 위해 구조-활성간 연구를 수행하였다. 이미 알려진 chalcone 유도체의 구조와 생물학적 활성 자료를 이용하여 구조-활성간 계산을 수행한 결과 새로운 화합물을 발견하였고, 이를 합성하여 효과를 측정한 결과를 보고하고자 한다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.960-960
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• 2005

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

• 생약학회지
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• 제31권3호
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• pp.273-279
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• 2000

Leukotriene $B_4\;(LTB_4)$ is a pro-inflammatory mediator synthesized in myeloid cells from arachidonic acid. Elevated levels of $LTB_4$ have been found in a number of inflammatory diseases and levels are related to disease activity in some of these. Because $LTB_4$ interacts with cells through specific cell surface receptors, $LTB_4$ receptor blockade is the most specific approach to reduce the pathogenic role of $LTB_4$. In order to find $LTB_4$ receptor antagonist from plants, we screened the $LTB_4$ receptor antagonistic activity of the methanol extract and solvent fractions of herbal drugs. The ability of samples to inhibit specific binding of $[^3H]-LTB_4$ to human peripheral neutrophils was used as assay to evaluate the antagonistic activity of plant materials. Among the tested methanol extracts of herbal drugs, Mori Radicis Cortex, Perillae Semen, Armeniacae Semen and Sophorae subprostratae Radix showed potent inhibitory activity above 70% at the concentration of $100\;{mu}g/ml$. The inhibitory activities of $LTB_4$ binding to human neutrophils were evaluated for several solvent fractions at three different concentrations. Especially, hexane soluble fractions of Anemarrhenae Rhizoma and Embeliae Radix, and ethyl acetate soluble fractions of Aristolochiae Fructus, Magnoliae Cortex and Zingiberis Rhizoma crudus showed moderate activity at $25\;{mu}g/ml$. These fractions were promising candidates for the study of the activity-guided chromatographic purification of active compounds. Silica gel column chromatography of hexane soluble fractions of Anemarrhenae Rhizoma and Embeliae Radix gave very active sub-fractions, AA-4 and ES-4, and their inhibition activities of $LTB_4$ binding to human neutrophil at $30\;{mu}g/ml$ were 78% and 62%, respectively. From these results we could anticipate new $LTB_4$ receptor antagonist from herbal drugs, and the block of $LTB_4$ effects may provide beneficial in neutrophil mediated diseases such as inflammation and bronchial asthma.

• 대한한의학회지
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• 제19권2호
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• pp.86-99
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• 1998

Antiallergic action and the effect on normal immune function of an oriental medical prescription Gegangjochohwangsinbutang (GJHB) water extract were examined in several experimental models. GJHB water extract at 600-1,800 mg/kg/day administered orally for one week significantly recuded the passive cutaneous anaphylaxis in rats in a dose-dependent manner. Whereas the extravasation induced by intradermal leukotriene D4 in rats was significantly inhibited by GJHB water extract at 600-1,800 mg/kg/day, po, for one week, but that by histamine or serotonin was not influenced. In a rat asthma model, the delayed airway resistance in ovalbumin-induced asthmatic response was significantly attenuated by GJHB water extract of 1,800 mg/kg/day, po, administered for one week. It was also found that GJHB water extract at 1 mg/kg concentration in vitro relaxed the isolated uinea pig trachea contracted by leukotrien D4, but not that by histamine. The above findings indicate that GJHB water extract can ameliorate the adverse effect of type Ⅰ allergy such as asthma. This pharmacological action seems to derive from an inhibition of GJHB water extract on leukotriene D4-related physiological change.

• Restorative Dentistry and Endodontics
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• 제25권2호
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• pp.193-201
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• 2000

Prostaglandins (PGs) and Leukotrienes (LTs) have been implicated in the genesis of pulpal and periapical inflammation. In this study, the relationships among $PGE_2$, 6-keto-PG $F_1{\alpha}$ (a stable metabolite of $PGI_2$) and $LTB_4$ concentrations in inflamed pulp and periapical lesions were discussed. Pulp tissue were obtained in routine endodontic treatment and periapical lesions in periapical surgery after clinical diagnoses were made. These specimens were divided into four groups as normal pulp group (Control group), acute pulpitis group, chronic pulpitis group, and periapical lesion group. Pulp tissue and periapical lesions were stored in liquid nitrogen. The concentration of $PGE_2$, $PGI_2$ and $LTB_4$ were measured with ELISA. The data were analyzed by one-way ANOVA. Significantly higher levels of $PGE_2$, 6-keto-PG $F_1{\alpha}$ a and $LTB_4$ were found in acute pulpitis group than chronic pulpitis group and periapical lesion group(p<0.05). Periapical lesion group showed significantly higher mean concentrations of $PGE_2$ and $LTB_4$ than chronic pulpitis group. In control and chronic pulpitis group, significant higher levels of $PGI_2$ than $PGE_2$ and $LTB_4$ were found. These results suggested that the high levels of $PGE_2$ and $LTB_4$ in periapical lesions may be due to rich endothelium., fibroblast and lymphocyte known as the main producers of $PGE_2$ and $LTB_4$. $PGI_2$ may be thought to one of the most abundant PGs in normal pulp tissue.

• 대한본초학회지
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• 제27권1호
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• pp.41-49
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• 2012

Objectives : The purpose of this study was to investigate the anti-oxidative and anti-atopic dermatitis effects of persimmon leaf extract obtained from Cheongdo-gun, where more than 60% of Korean persimmon is produced. Methods : Anti-oxidative effects of the crude persimmon leaf extract harvested monthly between May and November were determined by in vitro assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide dismutase (SOD)-like reaction. Anti-atopic dermatitis effects of the crude persimmon leaf extract were determined by using collagenase type I inhibition assay and by quantitative assays including serum histamine, prostaglandin E metabolite and leukotriene $B_4$ levels in animal model of atopic dermatitis using Balb/c mice. Results : Persimmon leaf extract harvested in May had higher levels of total phenolic compounds (182.24 mg/g) and flavonoids (23.05 mg/g) than the ones of different month extract. Also, persimmon leaf extract harvested in May showed the most effective extract scavenging activities of DPPH free radical ($13.39{\pm}0.21\;{\mu}g/ml$) and superoxide anion radical ($40.52{\pm}2.32\;{\mu}g/ml$), leading to use the persimmon leaf extract harvested in May for the experiments hereafter. Persimmon leaf extract showed $326.71{\pm}4.6\;{\mu}g/ml$ of 50% inhibitory concentration ($IC_{50}$) for collagenase type I which is responsible for the degradation of extracellular matrix. In addition, persimmon leaf extract application group could decrease serum levels of histamine, prostaglandin E metabolite and leukotriene $B_4$ compared to the negative control in animal model of atopic dermatitis. Especially, persimmon leaf extract showed a significantly decreased serum leukotriene $B_4$ level relative to the levels of histamine and prostaglandin E metabolite. Conclusions : Persimmon leaf extract showed anti-oxidative and anti-atopic dermatitis effects in vitro and in vivo. These results suggest that persimmon leaf extract may have immunoregulatory function for alleviating atopic dermatitis by decreasing collagenase activity and mast cell activation.

• Bulletin of the Korean Chemical Society
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• 제13권5호
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• pp.551-553
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• 1992

An efficient and very short synthesis of epoxy alcohol 5, a key intermediate for leukotriene synthesis, was described. The key reaction involves the regioselective benzylidene acetal formation from methyl 5,6,7-trihydroxyheptanoate 1.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.115.2-115.2
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• 2002

• BMB Reports
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• 제51권8호
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• pp.373-377
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• 2018

Triple-negative breast cancer (TNBC) is considered to be a notorious type of cancer due to its aggressive metastatic potential and poor prognosis. Recent evidence suggests that BLT2, a low-affinity $LTB_4$ receptor is critically associated with the phenotypes of TNBC cells, including invasion, metastasis, and survival. Furthermore, in a group of 545 breast cancer patients with metastasis, we observed that the high-BLT2 subgroup had a lower disease-free-survival rate than the low-BLT2 subgroup. Thus, we theorized that anti-BLT2 strategies could facilitate the development of new therapies used for TNBC. This review focuses on recent discoveries regarding BLT2 and its roles in as a novel prognostic biomarker in TNBC.