• Genomics & Informatics
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• 제6권3호
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• pp.110-116
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• 2008

Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels, and chronical elevation of blood pressure is known as hypertension. Although hypertension is affected by genetic and environmental factors, the genetic background of hypertension is not fully understood. One of the candidate genetic factors, Prostaglandin-endoperoxide synthase 2 (PTGS2), is a membrane-bound enzyme, catalyzing the conversion of arachidonic acid to prostaglandin, and recently SNPs of PTGS2 gene was associated with hypertension in Japanese population. Therefore the association of PTGS2 polymorphisms was investigated with blood pressure in healthy Korean subjects, 470 unrelated individuals randomly selected from Ansung and Ansan cohorts. The 25 SNPs of PTGS2 gene were identified by the sequencing analysis of 24 Korean samples. Among identified polymorphisms, three SNPs (rs689466, -1329A>G; rs5275, +6365T>C; rs4648308, +8806G> A) were selected for further association analysis, and rs689466 located in promoter region was associated with blood pressure as well as triglyceride level in the blood. By in silico analysis, rs689466 locates in v-Myb transcription factor binding site, and the v-Myb site disappears when the SNP is changed from A to G nucleotide. Individuals with A/G and G/G genotype in rs689466 have higher blood pressure than those with A/A genotype, and the regression p-value is 0.008 for systolic and 0.004 for diastolic blood pressure. In summary, the PTGS2 polymorphism (rs689466) is associated with blood pressure in Asian populations based on this and Japanese studies, shedding light on it as a genetic risk marker of hypertension.

• Korean Journal of Food Science and Technology
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• 제33권6호
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• pp.753-759
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• 2001

To evaluate antiinflammation of Aloe vera peel, antiimflammation substances were extracted from Aloe vera peel and identified, and we investigated the effect of the its substance the inhibitory effect on the activity of hyaluoronidase, elastase, collagenase and prostaglandin endoperoxide synthase. The water extract from Aloe vera peel were successfully purified with solvent fractionation, silica gel column chromatography, preparative thin layer chromatography and UV spectrometer. Two purified active substances were identified as aloe-emodin and barbaloin by Mass Spectrometer, $^1H-NMR$ and FT-IR. Aloe-emodin and barbaloin. $IC_{50}$ values of aloe-emodin and barbaloin against hyaluronidase activity were 40 and $70\;{\mu}g/mL$, respectively. Leuckocyte elastase, which is related to the destruction of various tissue, $IC_{50}$ values of them were 50 and $60\;{\mu}g/mL$, respectively. $IC_{50}$ values of aloe-emodin and barbaloin against collagenase activity were 40 and $60\;{\mu}g/mL$, respectively. and $IC_{50}$ values of aloe-emodin and barbaloin aganist the prostaglandin endoperoxide synthase, which play an important role in inflammatory reactions, were 40 and $70\;{\mu}g/mL$, respectively. Inhibitory effects of aloe-emodin, barbaloin and aspirin against carrageenan paw edema were 74.9, 52.9 and 51.9% as inhibiton percentage, respectively, at dose of 100 mg/kg and that of indomethancin was 49.7 at dose of 10 mg/kg. Cell cytotoxicity of barbaloin against human gingival cells was lower than that of aloe-emodin. Aloe-emodin and barbaloin did not show cytotoxicity against human gingival cells at concentration of 1.0 and $5.0\;{\mu}g/mL$, However, aloe-emodin and barbaloin showed less cytotoxicity than chlorhexidine, which usually have been used as the agent of anticaries and antiinflammation. These results suggested that aloe-emodin and barbaloin from Aloe vera peel have the effect of anticaries and antiinflammation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.21-22
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• 2001

Phospholipase A$_2$(PLA$_2$) comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids including arachidonic acid and lysophospholipids. Distinct forms of PLA$_2$are involved in digestion, inflammation, and intercelluar-and intracellular signaling pathways. The released arachidonic acid, which is enriched at the sn-2 position, serves as the precursor for eicosanoids such as prostaglandins and leukotrienes. During oxygenation of arachidonic acid to hydroxy endoperoxide, reactive oxygen radicals are generated. On the other hand, lysophospholipids increase membrane fluidity and can be cytotoxic with its detergent-like action. Thus, the biochemical features of the products of PLA$_2$activity suggest that PLA$_2$may be implicated in many destructive cellular processes.

• Biomaterials and Biomechanics in Bioengineering
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• 제1권2호
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• pp.73-79
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• 2014

Covalent attachment of 1, 4-dimethylnaphthalene (DMN) based endoperoxide forming subunits to a polyvinyl butyral (PVB) backbone has been achieved. The functionalized polymer materials prepared and characterized here can serve as biocompatible carrier systems for studying cellular uptake, intermediate storage and delayed release of singlet oxygen, which opens up new doors for optimizing a variety of medical applications of photogenerated DMN-endoperoxides such as antiviral, antibacterial, antiplasmodial and antitumor activity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1797-1802
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• 2014

Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.

• Journal of Ginseng Research
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• 제13권2호
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

• Parasites, Hosts and Diseases
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• 제61권1호
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• pp.33-41
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• 2023

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED₅₀ values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.851-855
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• 2002

Seven ergosterol derivatives (1-7) were isolated from silkworm larvae infected with Paecilomyces sp. J300. On the basis of spectroscopic means, their structures have been elucidated as 3$\beta$,5$\alpha$-dihydroxy-ergosta-7,22-diene (1), 5$\alpha$,6$\alpha$-epoxy-(22E,24R)-ergosta-8(14), 22-diene-3$\beta$,7$\alpha$-diol (2), 5$\alpha$,6$\alpha$-epoxy-(22E,24R)-ergosta-8, 22-diene-3$\beta$,7$\alpha$-diol (3), ergosta-4, 6, 8(14), 22-tetraene-3-one (4), ergosterol (5), ergosterol endoperoxide (6), 3$\beta$,5$\alpha$-dihydroxy-6$\beta$-methoxyergosta-7,22-diene (7). Compounds 3~7 showed moderate cytotoxicity against five tumor cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.121-121
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• 1998

Artemisia annua, an indigenous plant in Korea, contains a clinically important potent antimalarial principle, artemisinin. Artemisinin is a cadinane-type sesquiterpene endoperoxide. Cadinane synthase catalyzes the first committed step in artemisinin biosynthesis by cyclizing farnesyldiphosphate. In hopes of finding a cadinane synthase gene involved in artemisinin biosynthesis, oligonucleotides were synthesized on. the basis of the consensus nucleotide sequences and Nco I restriction sites for convenience in cloning. Specifically, nucleotide sequences of two highly conserved regions were deduced from the genes of similar function of Hyoscyamus muticus, Nicotiana tabacum, Abies grandis, Lycopersicon esculentum, and Gossypium hirsutum to construct a set of primers for polymerase chain reation (PCR). A 184 bp fragment was found to be amplified by PCR, and subsequently cloned. The gene revealed 62.8% identity in nucleotide and 55.6% in amino acid sequence to correspondent gene of N. tabacum. The gene was different from another sesquiterpene cyclase gene of A. annua, germacranadiene synthase gene, recently reported by Mercke and Bordelius (1998).

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.349-353
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• 2000

Mefenamic acid has been widely used as clinical drug for anti-inflammatory and analgesic. This drug was known to non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and indomethacin. Although the drugs which comprise this group are of diverse chemical structures, they all share the antipyretic, analgesic and anti-inflammatory actions which are characteristic of aspirin. Action of this drugs is caused by inhibitory effect of biosynthesis of prostaglandin that are synthesized from arachidonic acid via the endoperoxide biosynthesis pathway, the initial step of which is catalysed by cyclooxygenase. Mefenamic acid has more potent inhibitory action of prostaglandin biosynthesis than aspirin. Therefore, mefenamic acid is expected to have anticoagulant activity as aspirin-like drugs. This study was carried out to investigate the sinthesis of mefenamic acid derivatives from mefenamic acid and aromatic compound of antioxidant and its antioxidative and anticoagulant activities. Synthesis of mefenamic acid derivatives was conformed by conjugation as using esterification method. Biological activities was examined using effect of anticoagulant on bleeding time and effect of antioxidant by TBA method. As a result, SJ-202 showed strong antioxidative activity and anticoagulant activity among tested 4 compounds and exhibited similar activity to aspirin at anticoagulant activity.