• Archives of Pharmacal Research
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• v.29 no.8
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• pp.617-623
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• 2006

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2\;(PGD_2)$ and leukotriene $C_4\;(LTC_4)$ in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with ${\beta}-sitosterol$ (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.109-117
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• 2003

Arachidonic acid(AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2(PLA_2)$ enzymes and is sequentially converted to cyclooxygenase (COX) and lipoxygenase (LOX) then to various bioactive prostaglandins (PGs,) and leukotrienes (LTs). In order to find the specific inhibitors of AA metabolism enzymes such as $PLA_2$, COX-2, 5-LO and lyso PAF acetyltransferase. 195 Korean indigenous plant extracts were evaluated for their inhibitory activity on $PGD_2,\;LTC_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of eight plants such as Saururus chinensis, Aster tataricus, Chrysanthemum cinerariaefolium, Reynoutria japonica, Disocorea nipponica, Epimedium koreanum, impatiens textori, Veronica rotunda var. subintegra were found to inhibit production of inflammatory mediators in vitro assay system.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.634-640
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• 2017

Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration. The severity score and scratching behavior were alleviated in the rifampicin-treated group. Serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels were also ameliorated in mice treated with rifampicin. We next examined whether rifampicin has anti-atopic activity via suppression of mast cell activation. Rifampicin suppressed the release of ${\beta}$-hexosaminidase and histamine from human mast cell (HMC)-1 cultures stimulated with compound 48/80. Treatment with rifampicin also inhibited secretion of inflammatory mediators, such tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) and prostaglandin $D_2$ ($PGD_2$), in mast cells activated by compound 48/80. The mRNA expression of cyclooxygenase 2 (COX-2) was reduced in the cells treated with rifampicin in a concentration-dependent manner. These results suggest that rifampicin can be used to treat atopic dermatitis.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.84-93
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• 1993

It has been reported that ginseng is effective in the central nervous system, immune system, and the strong inflammatory responses. However, there has been no research report yet about the effect of ginseng on allergic hypersensitivity reactivity. To confirm the ginseng effects on the release of mediators(histamine. leukotrienes etc.) which cause the hypersensitivity reactivity and inflammatory response, we used actively sensitized guinea pig airway tissues by utilizing the superfusion technique. In this procedure. the contractile response and mediators released after antigen stimulation of sensitized tissues, and IgG and IgE antibody products were measured in sera of immunized animals. Then the results of the controll group were compared to those of ginseng pretreatment groups. In the total saponin(TS) and panaxatriol(PT) pretreatment, histamine release decreased by $20\%$ in the tracheal tissues after active sensitization by ovalbumin(OVA, 10mg/kg), but in the lung parenchyma, histamine release decreased by $40\%.$ Panaxadiol(PD) significantly decreased histamine release by $40\%$ in the both tissues after active sensitization. TS, PT and PD of ginseng poorly blocked leukotrienes (LTs) and prostagrandin $D_2(PGD_2)$ release(less than $10\%$). Ginseng TS and PT had no effect on the serum IgG antibody production by ovalbumin, whereas PD significantly increased serum IgG antibody contents(approximately by 2 times). However, $IgG_1$ antibody products in the serum of guinea pig actively sensitized with ovalbumin after PD pretreatment were decreased, compared to that with ovalbumin alone. IgE antibody production by passive cutaneous anaphylaxis(PCA) titer in the TS pretreatment increased 3 times more than in the absence of TS(PCA titer by PT was not detected). These studies show that some ginseng saponins can in part act to inhibit mediator release in antigen - induced airway smooth muscle by inducing the IgG antibody production which has been changed in the specificity.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.168-168
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• 2017

Drought conditions during cultivation reduce agricultural production yield less than a theoretical maximum yield under normal condition. Plant specific NAC transcription factors in rice are known to play an essential roles in stress resistance transcriptional regulation. In this study, we report the rice (Oryza sativa L japonica) NAM, AFTF and CUC transcription factor OsNAC17, which is predominantly induced by abiotic stress in leaf, was contribute to the drought tolerance mediated reactive oxygen species (ROS) in transgenic rice plants. Constitutive (PGD1) promoter was introduced to overexpress OsNAC17 and produced the transgenic PDG1:OsNAC17. Overexpression of OsNAC17 throughout the whole plant improved drought resistance phenotype at the vegetative stage. Morphological characteristics such as grain yield, grain filling rate, and total grain weight improved by 22~64% over wild type plants under drought conditions during the reproductive stage. The improved drought tolerance in transgenic rice was involved in reducing stomatal density up to 15% than in wild type plants and in increasing reactive oxygen species-scavenging enzyme. DEG profiling experiment identified 119 up-regulated genes by more than twofold (P<0.01). These genes included UDP-glycosyltransferase family protein, similar to 2-alkenal reductase (NADPH-dependent oxireductase), similar to retinol dehydrogenase 12, Lipoxygenase, and NB-ARC domain containing protein related in cell death. Furthermore, OsNAC17 was act as a transcriptional activator, which has an activation domain in C-terminal region. These result demonstrate that the overexpression of OsNAC17 improve drought tolerance by regulating ROS scavenging enzymes and by reducing stomatal density

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.18 no.2
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• pp.456-477
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• 2024

With information technology's rapid development, the Internet faces serious security problems. Studies have shown that malware has become a primary means of attacking the Internet. Therefore, adversarial samples have become a vital breakthrough point for studying malware. By studying adversarial samples, we can gain insights into the behavior and characteristics of malware, evaluate the performance of existing detectors in the face of deceptive samples, and help to discover vulnerabilities and improve detection methods for better performance. However, existing adversarial sample generation methods still need help regarding escape effectiveness and mobility. For instance, researchers have attempted to incorporate perturbation methods like Fast Gradient Sign Method (FGSM), Projected Gradient Descent (PGD), and others into adversarial samples to obfuscate detectors. However, these methods are only effective in specific environments and yield limited evasion effectiveness. To solve the above problems, this paper proposes a malware adversarial sample generation method (PixGAN) based on the pixel attention mechanism, which aims to improve adversarial samples' escape effect and mobility. The method transforms malware into grey-scale images and introduces the pixel attention mechanism in the Deep Convolution Generative Adversarial Networks (DCGAN) model to weigh the critical pixels in the grey-scale map, which improves the modeling ability of the generator and discriminator, thus enhancing the escape effect and mobility of the adversarial samples. The escape rate (ASR) is used as an evaluation index of the quality of the adversarial samples. The experimental results show that the adversarial samples generated by PixGAN achieve escape rates of 97%, 94%, 35%, 39%, and 43% on the Random Forest (RF), Support Vector Machine (SVM), Convolutional Neural Network (CNN), Convolutional Neural Network and Recurrent Neural Network (CNN_RNN), and Convolutional Neural Network and Long Short Term Memory (CNN_LSTM) algorithmic detectors, respectively.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.345-357
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• 2005

Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. ${\Delta}^{12}-PGJ_2$ is a natural $PGD_2$ metabolite that is formed in vivo in the presence of plasma. It is known for ${\Delta}^{12}-PGJ_2$ to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhEMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of ${\Delta}^{12}-PGJ_2$ or mixture of 10-8M of ${\Delta}^{12}-PGJ_2$ and 100ng/ml of rhBMP-2 or 100ng/ml of rhEMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ inhibited cell proliferation of human osteosarcoma cells. 2. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated alkaline phosphatase activity significantly higher than ${\Delta}^{12}-PGJ_2$ alone. 3. rhBMP-2 or mixture of rhEMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated mineralization compared to ${\Delta}^{12}-PGJ_2$ alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with ${\Delta}^{12}-PGJ_2$/rhBMP-2, rhBMP-2 alone, ${\Delta}^{12}-PGJ_2$ alone. These results show that mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 causes more bone formation than ${\Delta}^{12}-PGJ_2$ alone while the bone formation effects of mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.133-152
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• 2005

1. 목적 Prostaglandin은 치주질환과 관련된 국소적 골 대사에 중요한 역할을 한다. ${\Delta}^{12}PGJ_2$는 생체 내에서 혈장의 존재 하에 형성되는 천연 $PGD_2$ 대사산물이며 peroxisome- proliferator에 의해 활성화되는 감마 수용체 (PPAR ${\Gamma}$)에 대해 높은 친화성을 갖는 리간드로서 핵 수용체군에 속하는 전사조절인자이다. 이 연구의 목적은 골화 과정에서 ${\Delta}^{12}PGJ_2$의 역할을 규명하기 위해, 조골세포주의 증식과 분화에 미치는 영향과 그에 관련된 세포기전을 조사하는 데에 있다. 2. 방법 인간 골육종세포주인 Saos-2 (ATCC.HTB 85)와 쥐의 조골세포주 (MC3T3-E1)를 배양한 후 실험군에 농도가 각각 $10^{-5}$, $10^{-6}$, $10^{-7}$, $10^{-8}$, $10^{-9}$ 몰인 ${\Delta}^{12}PGJ_2$와 ciglitazone (합성 PPAR 감마 길항체)를 첨가하였다. 조골세포에서 PPAR 감마의 발현을 관찰하기 위해 역전사효소-중합효소연쇄반응(RT-PCR)을 특정한 primer를 이용하여 시행하였다. 세포 증식은 1일, 2일, 3 일째에 MIT 분석법으로 측정하였고, 2 일째에 알칼리성 인산효소 (ALPase) 생산을 측정하였다. 위의 결과에서 얻은 적정한 농도에서 다양한 조골세포 분화의 표지자들-제 1 형 교원질, 알칼리성 인산효소, osteopontin 및 bone sialoprotein-에 대한 간이 정량적 역전사효소-중합효소연쇄반응 (semiquantitative RT-PCR)을 실시하였으며 골결절 형성에 대한 효과를 알아보고자 석회화 분석도 시행하였다. 3. 결과 ${\Delta}^{12}PGJ_2$와 ciglitazone 모두 Saos-2 세포주의 증식을 촉진시켰다 .$10^{-8}$ 몰의 ${\Delta}^{12}PGJ_2$와 $10^{-6}$몰의 ciglitazone을 첨가한 실험군을 대조군과 비교했을 때, 시간에 비례하여 세포 증식률이 증가되었다. 알칼리성 인산효소의 활성화 검사에서도 증식률에서와 유사한 결과를 보여주었다. 간이 정량적 RT-PCR에서는 ${\Delta}^{12}PGJ_2$로 처리한 군의 경우 제 1 형 교원질, 알칼리성 인산효소, osteopontin, 그리고 bone sialoprotein의 상대적 mRNA 수준이 유의하게 높았다. 석회화 분석에서는 MC3T3-E1 세포를 $10^{-6}$ 몰의 ${\Delta}^{12}PGJ_2$로 처리한 군과 $10^{-5}$ 몰의 ciglitazone으로 처리한 군에서 현저한 골결절 형성을 보였다. 이러한 결과들은 ${\Delta}^{12}PGJ_2$가 유용한 골 유도물질이 될 수 있으며 또한 그 작용기전이 PPAR 감마-의존형 경로와 연관되어 있음을 보여준다.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.