• 대한한의학회지
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• 제29권5호
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.

• 약학회지
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• 제26권1호
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• pp.1-8
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• 1982

Derivation of triterpenoids and then the screening for corticomimetics among them is our primary interest. $C_{11}$-oxo-triterprenoids except glycyrrhetinic acid are rarely found in the plant kingdom. Based on the facts that $C_{3}$ and $C_{11}$-Oxo-group are essential for the corticoid-like-activity through its competitive inhibition on the corticoid-5.betha.-reductase, it was attempted to produce artificial inhibitor on the enzyme by introducing $C_{11}$-oxo group to the triterpenoids of oleanene series such as oleanolic acid and hederagenin. We could obtain the $C_{11}$-oxo-oleanolic acid m.p. $264-6^{\circ}$, uv ${\lambda}max$ 249 and $C_{11}$-oxo-hederagenin amorp. uv ${\lambda}max$ 251 by acetylation, $CrO_{3}$-oxid., and deacetylation. Glycyrrhetinic acid, a natural 11-oxo-compound and the other 11-oxo-derivatives of oleanolic acid and hederagenin were compared in their inhibitory activity on the corticoid-5.betha.-reductase. The inhibitory activity of those compound were decreased in the order of $C_{11}$-oxo-oleanolic acid, $C_{11}$-oxo- hederagenin, glycyrrhetinic acid. This suggests more strong corticomimetic activity of those artificially derived $C_{11}$-oxo-oleanolic acid and $C_{11}$-oxa-hederagenin. Their Ki value were $4.6{\times}10^{-4}M$ and $5.8{\times}10^{-4}M$ respectively.

• 한방안이비인후피부과학회지
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• 제15권2호
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• pp.33-52
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• 2002

The effects of Arctii fructus extract on allegenic inflammation were investigated using in vivo and in vitro test models. Firstly, the cytotoxicity of Arctii fructus extract was validated using MTT assay. As a result, Arctii fructus extract showed no cytotoxic potential, while SDS, a positive control, revealed strong cytotoxic effect. In LLNA assay, Arctii fructus extract showed no skin allergenicity. Next, the anti-allergic actions of Arctii fructus extract were evaluated using rodent experimental models. The oral, intraperitoneal and intradermal administration of Arctii fructus extract significantly inhibited the compound 48／80-induced vascular permeability documented by Evans blue extravasation. In addition, Arctii fructus extract showed potent inhibitory effect on passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, Arctii fructus extract revealed to possess inhibitory potential on the compound 48／80-induced histamine release from rat peritoneal mast cells. Moreover, Arctii fructus extract inhibited the IL-4 and TNF-${\alpha}$ mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Finally, it revealed that Arctii fructus extract significantly suppressed histamin-provoked antigenic inflammation reactions in human prick test. Taken together, these results suggest that anti-allergic action of Arctii fructus extract may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

• 통합자연과학논문집
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• 제13권4호
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• Korean Journal of Chemical Engineering
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• 제35권11호
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• pp.2313-2320
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• 2018

Tetramethylene-1,4-bis(N,N-dodecylammonium bromide), cationic gemini surfactant, (12-4-12) was first synthesized with an one-step and shortened procedure and its interfacial and antimicrobial properties were compared with a conventional single-chain cationic surfactant, cetyltrimethylammonium bromide (CTAB). The interfacial and thermodynamic properties of both surfactants reveal that critical micelle concentration (CMC) of this novel synthetic cationic dimeric surfactant is lower than that of cationic monomeric surfactant at almost 15 times of its magnitude, which is due to the increase in hydrophobicity of the surfactant molecules by having dual hydrocarbon chains. In comparison with CTAB, the produced compound 12-4-12 yields much better interfacial and thermodynamic properties. The antimicrobial activities of the synthesized gemini surfactant were tested against eight strains of bacteria, as well as two strains of fungi. The results showed that both 12-4-12 compound and CTAB exhibited higher inhibitory effects on the growth of Gram-positive bacteria and fungi than that of Gram-negative bacteria. The minimum inhibitory concentrations in molar of 12-4-12 against all tested Gram-negative bacteria were lower than those of CTAB, which is hypothetically due to the lower HLB together with smaller CMC values of our gemini surfactant.

• Natural Product Sciences
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• 제26권4호
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• pp.340-344
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• 2020

A new chromone analogue (1) was isolated from an EtOAc-extract of Pleosporales sp. culture medium, together with five known chromones (2 - 6). The isolation workflow was guided by a Molecular Networking-based dereplication strategy. The chemical structure of the new compound was elucidated using NMR and MS spectroscopy, and the absolute configuration was established by the Mosher's method. All isolated compounds were evaluated for their inhibitory effects on lipopolysaccharide-induced nitirc oxide production in RAW 264.7 macrophages. Compound 1 showed marginal inhibitory activity with an IC50 value of 118.7 μM.

• 대한한의학회지
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• 제18권2호
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• pp.167-186
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• 1997

The inhibitory activity of Aquillariae Lignum (Thymelaeaceae) on type Ⅰ immediate hypersensitivity of the anaphylactic type in the wistar rat model of passive cutaneous anaphylaxis, an IgE-mediated, mast cell-dependent reaction. Administered orally at 250, 500 mg/kg body weight 1 h before the challenge, Aquillariae Lignum potently inhibited PCA in rats which disodium cromoglycate showed poor inhibitory activity. Aquillariae Lignum inhibited compound 48/80-induced anaphylaxis 100% with a dose of 0.5 g/kg body weight at 1 h before or 5 and 10 min after injection of compound 48/80. Aquillariae Lignum (0.05-1.6 mg/ml) also exhibited the dose-related inhibitory effect on compound 48/80-induced histamine release from rat_peritoneal mast cells. Moreover, it was clearly demonstrated that Aquillariae Lignum and disodium cromoglycate disodium cromoglycate potently inhibited such type Ⅰ allergic reactions as anaphylactic shocks, suggesting that these drugs, at least in part, share the same mechanism of action It is suggested that Aquillariae Lignum may exert a stronger inhibition on the mast cell degranulation process. Since Aquillariae Lignum (1.0 mg/ml) inhibited about 90% of histidine decarboxylase activity, the inhibitory activity of Aquillariae Lignum for histamine release was considered to be derived from the inhibition of histidine decarboxylase activity. It results from increased expression of the mRNA coding for histidine decarboxylase, as assessed by Northern blot analysis after a 12 h incubation to P-815 cells with dexamethasone plus 12-O-tetradecanoylphorbol-13-acetate. The addition of Aquillariae Lignum to P-815 cells with dexamethasone plus 12-O-tetradecanoyl-phorbol-13-acetate, significantly inhibited the histidine decarboxylase gene expression. Tumor necrosis $factor-{\alpha}$ was not constitutively expressed in P-815 cells. Substance P selectively activates the tumor necrosis $factor-{\alpha}$ gene expression in P-815 cells. Aquillariae Lignurm inhibited substance P-induced tumor necrosis $factor-{\alpha}$ gene expression. Furthennore, The effect of Aquillariae Lignum on the mRNA expression of novel protein kinase C ${\delta}$ a major isoform of mast cells, was examined by Northern blot analysis. The expression of novel protein kinase C ${\delta}$ mRNA in the presence of Aquillariae Lignum was significantly lower than in the absence of Aquillariae Lignum. These results suggest the possibility that the inhibition of allergic reaction by Aquillanae Lignum should be regulated by tumor necrosis $factor-{\alpha}$ and novel protein kinase C ${\delta}$.

• 대한화장품학회지
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• 제36권3호
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• pp.233-240
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• 2010

신규 미백 소재 개발을 위하여 tyrosinase의 활성을 억제하는 천연물과, alpha-melanocyte stimulating hormone ($\alpha$-MSH)을 저해하는 펩타이드를 결합한 소재를 고체상 합성법으로 제조하였다[1,2]. Tyrosinase 활성 억제 효능이 있는 천연유래물질을 기존 연구를 바탕으로 선정하였으며, 이중에서 상업화 된 물질 17종에 대해 Mushroom Tyrosinase 활성 억제 효과를 측정하여, 그 중 caffeic acid, coumaric acid를 선별하였다. 펩타이드는 $\alpha$-MSH 분비를 억제하며, tyrosinase활성을 억제하는 것으로 알려진 melanostatin을 선정하였으며[3-5], PLG-$NH_2$ (Proline-Leucine-Glycine-$NH_2$) 중에서 유도체화 수율의 저하 원인으로 예상되는 Proline (Pro)의 서열을 다른 아미노산으로 변경하면서 선별된 천연물인 coumaric acid와 caffeic acid에 도입하였다. 또한 최종물질의 원가를 고려하여 acid-amide 형태를 acid형태로 전환한 유도체를 합성하였다. 이들 펩타이드 유도체들에 대해서 B16F1 melanoma cell에서의 멜라닌 생성 억제 효능을 평가하여 유도체화된 물질이 기존의 천연유래물질이나 펩타이드에 비하여 높은 저해효과를 가지는 것을 확인하였다.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.685-690
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• 2005

We recently reported that the ginseng saponin metabolite, compound K (20-O-$\beta$-D-glucopyra-nosyl-20(S)-protopanaxadiol, IH901), inhibits the growth of U937 cells through caspase-dependent apoptosis pathway. In this study, we further characterized the effects of compound K on U937 cells and found that, in addition to apoptosis, compound K induced the arrest of the G1 phase. The compound K treated U937 cells showed increased p21 expression; an inhibitory protein of cyclincdk complex. The up-regulation of p21 was followed by the inactivation of cyclin D and the cdk4 protein, which act at the early $G_1$ phase, and cyclin E, which acts at the late $G_1$ phase. Furthermore, compound K induced the activation of JNK and the transcription factor AP-1, which is a downstream target of JNK. These findings suggest that the up-regulation of p21 and activation of JNK in the compound K treated cells contribute to the arrest of the $G_1$ phase.

• Journal of the Korean Wood Science and Technology
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• 제26권4호
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• pp.78-85
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• 1998

산초나무 각 부위별 알코올추출물의 피부사상균에 대한 항균활성은 근피 추출물에서 가장 높게 나타났으며, 각 용매별 분획분의 항균활성은 근피부의 petroleum ether 분획에서 가장 높게 나타났다. 항균활성성분을 분리하기 위해 항균력이 가장 높게 나타난 근피알코올추출물의 petroleum ether 분획분을 silica gel column chromatography를 실시하였으며, 항균활성성분인 CI과 CII가 분리되었다. CI과 CII의 MIC을 측정한 결과 CI의 MIC은 $40{\mu}g/m\ell$였으며, $20{\mu}g/m\ell$의 농도에서도 균액의 접종흔적이 조금 남아있었을 뿐 균사의 생장은 관찰할 수 없었다. 또한 CII의 MIC은 $800{\mu}g/m\ell$였으며, $600{\mu}g/m\ell$의 농도에서도 균액의 접종흔적이 조금 있었을 뿐 다른 농도에서처럼 균사의 생장은 관찰할 수 없었다. 기기 분석 결과 CI과 CII는 기지(旣知)의 alkaloid 화합물들이었다.