• IMMUNE NETWORK
• /
• 제21권3호
• /
• pp.22.1-22.17
• /
• 2021

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

• 한국식품과학회지
• /
• 제23권1호
• /
• pp.68-75
• /
• 1991

차과의 일종인 후피향의 종실유에는 틀리글리세리드가 92.4%로 대부분을 차지하고 있었으며, 소량성분으로 극성지절이 5.9%, 스테롤이 1.2%, 색소가 0.5%였다. 지방산 조성을 보면 C18 : 1(36.1%), C18 : 2(30.9%), C16 : 0(15.1%) C16 : (7.6%) 및 C18 : 0(3.4%)가 중요한 성분이었으며, 매우 흥미롭게도 cyclopropane 고리가 탄소 11, 12에 위치한 cis-11, 12-methylene octadecanoic acid가 4.8% 함유되어 있었다.

• 한국수산과학회지
• /
• 제19권1호
• /
• pp.45-51
• /
• 1986

D-glucose-glycine 계를 사용하여 Maillard 반응에 의하여 생성되는 저분자 휘발성성분을 비롯하여 amide 화합물의 생성 및 그 기구를 검토하였다. 그 결과, 동정된 저분자 휘발성성분 중에서, headspace gas 중의 휘발성성분은 furan, acetone, 2-methylfuran, 2,5-dimethylfuran 2-butanone 2,3-pentanedione, diacetyl 등이었다, 이 중에서 diacetyl의 생성량이 가장 많아, 전 peak 면적의 약 $70\%$를 차지하였다. 또한, 에테르 추출물중의 주요반응생성물은 초산, furfuryl alcohol 2,5-dimethylpyrrole 2-acetylpyrrole 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one 등이었고, ethyl acetate 로 추출한 산성획분중에는 N-acetyl-glycine와 N-methylacetamide 등 2종류의 amide 화합물의 생성이 밝혀졌다. 이들 amide 화합물적 생성기구를 밝히기 위하여, Mailiard 반응초기생성물인 diacetyl 및 glyoxal을 각각 butylamine과 반응시킨 결과, Schiff 염기의 산화적 분해로 N-butylacetamide 및 N-butylformamide의 생성이 인정되었다. 따라서 N-acetylglycine 및 N-methylacetamide는 glucosylamine의 2,3-enol 화 및 ${\beta}-elimination$에 의한 탈수의 진행으로 생성된 dicarbonyl 화합물이 glycine과 반응하여 Schiff 염기를 형성하고, 이 Schiff 염기가 산화적분해를 받아서 N-acetylglycine이 생성되고, N-methylacetamide는 N-acetylglycine의 탈탄산에 의해서 생성된다고 생각한다.

• 동의생리병리학회지
• /
• 제19권3호
• /
• pp.802-810
• /
• 2005

The tetrahydroisoquinolines included potent cytotoxic agents that showed antitumor activity,antimicrobial activity, and other biological properties. We studied the effect of CDST, 1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a newly synthesized anti-cancer agent. The cytotoxic activity of CDST in HL-60 cells was increased in a dose-dependent manner. CDST, tetrahydroisoquinolines derivative, was cytotoxic to HL-60 cells, with IC50 of $80{\mu}g/ml$. Treatment of CDST to HL-60 cells showed the fragmentation of DNA in a dose- and time dependent manner, suggesting that thesecells underwent apoptosis. Treatment of HL-60 cells with CDST was induced in a dose- and time-dependent activation of caspase-3, caspase-8 and proteolytic cleavage of poly(ADP-ribose) polymerase. In caspase activity assay, caspase-3 and -8 was activated after 12 h and 6 h posttreatment, respectively. CDST also caused the release of cytochrome c from mitochondria into the cytosol. CDST-induced cytochrome c release was mediated by caspase-8-dependent cleavage of Bid and Bax translocation. These results suggest that caspase-8 induced Bid cleavage and Bax translocation, caused mitochondrial cytochrome c release, and induce caspase-3 activationduring CDST-induced apoptosis in HL-60 cells.

• Archives of Pharmacal Research
• /
• 제28권12호
• /
• pp.1358-1364
• /
• 2005

In this study, we investigated whether a novel anti-ischemic $K_{ATP}$ opener KR-31378 [(2S,3S,4R)­N'-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2 -methly-2-dimethoxymethly-2H-benzopyran-4-yl)­N'-benzylguanidine] has protective effect against oxidative stress-induced death in heart-derived H9c2 cells. Cell death was induced by BSO, butionine sulfoximine, which inhibits GSH synthesis and subsequently increases reactive oxygen species (ROS) level. Cell death was quantitatively determined by measuring lactate dehydrogenase (LDH) activity and stained by Hoechst 33258. BSO-induced ROS production and mitochondrial membrane potential (MMP) were measured using 2',7'-dichlorofluorescein diacetate oxidation and rhodamine 123, respectively. Both the LDH release and the ROS elevation induced by treatment of H9c2 cells with 10 mM BSO, were significantly decreased by KR-31378. These protective effect and antioxidant effect of KR-31378 appeared to be independent on $K_{ATP}$ channel opening. Cells exposed to BSO showed an early reduction in MMP, and this reduction in MMP was significantly reversed by treatment with KR-31378. Caspase-3 activity in BSO treated H9c2 cells was remarkably increased, and this increased caspase-3 activity was significantly reversed by KR-31378. In conclusion, our results suggest that KR-31378 can produce cardioprotective effect against oxidative stress-induced cell death through antioxidant mechanism.

• 한국환경농학회지
• /
• 제37권2호
• /
• pp.117-124
• /
• 2018

본 연구에서는 HPLC-UVD/MS를 이용하여 농산물 중 oxanthiin 살균제인 oxycarboxin의 잔류 분석법을 확립하였다. 대표 농산물은 현미, 콩, 배추, 고추 및 사과를 선정하였고 acetone을 가하여 추출된 oxycarboxin 성분을 dichloromethane 액-액 분배법과 Florisil 흡착크로마토그래피법으로 정제하여 HPLC-UVD/MS 분석대상 시료로 사용하였다. Oxycarboxin의 정량적 분석을 위한 최적 분석 조건을 확립하였으며, 정량한계(LOQ)는 0.04 mg/kg 이었다. 각 대표 농산물에 대해 정량한계, 정량한계의 10배 및 50배 수준에서 회수율을 검토한 결과 모든 처리농도에서 78.3~96.1% 수준을 나타내었으며, 반복 간 변이계수(CV)는 최대 4.7%를 나타내어 잔류분석 기준인 회수율 70~120% 및 분석오차 10% 이내를 충족시키는 만족한 결과를 도출하였으며, LC/MS SIM을 이용하여 실제 농산물 시료에 적용하여 재확인 하였다. 이상의 결과로 신규 oxycarboxin의 HPLC-UVD/MS 분석법은 검출한계, 회수율 및 분석오차 면에서 국제적 분석기준을 만족하는 신뢰성이 확보된 정량 분석법으로 사용 가능할 것이다.

• 생명과학회지
• /
• 제18권11호
• /
• pp.1499-1506
• /
• 2008

식용 및 약용으로 이용되는 산초(Zanthoxylum schinifolium)의 줄기로부터 항암활성 성분을 분리하기 위하여, 산초 줄기를 유기용매로 추출하고 각 추출물의 인체 급성백혈병 암세포에 대한 독성 및 세포자살 유도 활성을 조사하였다. Methanol (SS-7), methylene chloride (SS-8), ethyl acetate (SS-9), n-butanol (SS-10)로 추출한 각 시료와 유기용매 추출 후 잔여분획 (SL-14)의 세포 독성을 인체 급성백혈병 Jurkat T 세포주를 대상으로 조사한 결과, 암세포에 대한 세포독성이 주로 methylene chloride 추출분획인 (SS-8)에서 확인되었다. Methylene chloride 추출물 (SS-8)의 Jurkat T 세포주에 대한 세포독성의 기전은 mitochondria로부터cytochrome c 방출, caspase-9 및 caspase-3의 활성화, PARP 분해, internucleosomal DNA fragmentation 등의 일련의 생화학적 반응을 수반하며, 항 세포자살단백질인 Bcl-xL단백질의 과발현에 의해 억제되는 세포자살 기전임을 확인하였다. FADD가 disruption된 Jurkat T cell clone I2.1 ($FADD^{-/-}$) 및 caspase-8가 결핍된 Jurkat T cell clone I9.2 (caspase-$8^{-/-}$)와 함께 the wild-type Jurkat T cell clone A3에 미치는 SS-8의 세포독성작용을 비교 분석한 결과, wild-type Jurkat A3, FADD-deficient Jurkat clone I2.1및 caspase-8-deficient Jurkat clone I9.2 모두는 SS-8의 세포독성에 대해 유사한 정도의 감수성을 나타내었다. 이는 SS-8에 의해 유도되는 apoptosis에 있어서, Fas/FasL system이 관계되지 않음을 시사한다. 한편, SS-8를 GC-MS 분석하여, 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4-(1-methylethylidene)-2-(4-nitrophenyl)- 3H-pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien-1-ol (13.73%), 5,6-dimethoxy- 2-methyl benzofuran (10.95%), 그리고 4-methoxy-2-methylcinnamic acid (5.38%) 등을 포함한 16가지의 구성 성분과 그 조성비를 확인하였다. 이상의 연구결과는 산초 줄기에 함유된 항암 활성에 대한 규명과 이해를 증진시킨다.

• 약학회지
• /
• 제38권3호
• /
• pp.265-273
• /
• 1994

ln vitro and in vivo antibacterial activities of DWQ-013(1-cyclopropyl-6,8-difluoro-7-(3-methylthiomethylpyrrolidinyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid), a new fluoroquinolone antibacterial agent, were compared with those of ciprofloxacin, sparfloxacin and ofloxacin against aerobic and anaerobic standard strains and clinical isolates. DWQ-013 had a broad spectrum and potent antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of DWQ-013 against Staphylococcus aureus was equal to that of sparfloxacin(SPFX) and superior to those of ciprofloxacin(CPFX). The antibacterial activity against Gram-negative bacteria was slightly lower than those of ciprofloxacin and sparfloxacin. MIC of DWQ-013 against Pseudomonas aeruginosa$(0.781{\sim}1.563\;{\mu}g/ml)$ was usually equal to that of sparfloxacin$(0.781\;{\mu}g/ml)$ and was inferior to that of ciprofloxacin$(0.098\;{\mu}g/ml)$. The number of viable cells was decreased rapidly after addition of DWQ-013 at concentration of $1{\sim}2$ folds of MIC.

• The Korean Journal of Physiology and Pharmacology
• /
• 제13권5호
• /
• pp.401-408
• /
• 2009

$K^+$-$Cl^-$-cotransport (KCC) has been reported to have various cellular functions, including proliferation and apoptosis of human cancer cells. However, the signal transduction pathways that control the activity of KCC are currently not well understood. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signal in the regulatory mechanism of KCC activity. Exogenous application of AA significantly induced $K^+$ efflux in a dose-dependent manner, which was completely blocked by R-(+)-[2-n-butyl-6,7 -dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1Hinden-5-yl]oxy]acetic acid (DIOA), a specific KCC inhibitor. N-Ethylmaleimide (NEM), a KCC activatorinduced $K^+$ efflux was significantly suppressed by bromoenol lactone (BEL), an inhibitor of the calciumindependent $PLA_2$ ($iPLA_2$), whereas it was not significantly altered by arachidonyl trifluoromethylketone ($AACOCF_3$) and p-bromophenacyl bromide (BPB), inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. NEM increased AA liberation in a doseand time-dependent manner, which was markedly prevented only by BEL. In addition, the NEM-induced ROS generation was significantly reduced by DPI and BEL, whereas $AACOCF_3$ and BPB did not have an influence. The NEM-induced KCC activation and ROS production was not significantly affected by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, markedly produced ROS and activated the KCC. Collectively, these results suggest that $iPLA_2$-AA signal may be essentially involved in the mechanism of ROS-mediated KCC activation in HepG2 cells.

• Applied Biological Chemistry
• /
• 제46권4호
• /
• pp.361-366
• /
• 2003

필발 열매로부터 추출 및 분리한 piperlongurnine (1-[3-(3,4,5-trimethoxyphenyl)acryloyl]-5,6-dihydro-1H-pyridin-2-one)이 aflatoxin $B_1\;(AFB_1)$ 생성억제에 있어서 탁월한 효과가 입증되어 3,4,5-trimethoxycinnamic acid (TMCA)를 모체로 하여 1-piperidin-1-yl-3-(3,4,5-trimethoxyphenyl)propenone (1), 1-morpholin-4-yl-3-(3,4,5-trimetholfrphenyl)propenone (2), 1- (3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)propenone (3), 1-(2-methylperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)propenone (4), 1- (3-hydroxypiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)propenone (5), 1-[3-(3,4,5-trimethoxy-phenyl)acryloyl]piperidin-2-one (6) 및 ethyl 1-[3-(3,4,5-trimethoxyphenyl)acryloyl]piperidin-4-carboxylate (7)의 유도체를 합성하여 구조를 확인하고, 이 화합물들을 이용하여 $AFB_1$ 생성저해 효과를 측정하였다. Aspergillus flavus NRRL 2061로부터 생성되는 $AFB_1$ 생성저해에 대한 실험한 결과 모든 유도체 화합물에서 활성을 나타내었으며, 특히 화합물 (3)이 1000, 500, 250, 100및 $50\;{\mu}g/ml$에서 100, 95, 90, 53 및 10%의 생성저해를 나타냈다. 이러한 연구 결과 유도체 화합물 (3)은 항진균 독소제 개발을 위한 선도화합물로 이용하여 새로운 농약으로 개발이 가능할 것이라고 판단된다.