• Title/Summary/Keyword: Epoxide hydrolase

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Low Microsomal Epoxide Hydrolase Expression is Associated with Bladder Carcinogenesis and Recurrence

  • Zhang, Zhe;Yu, Xiu-Yue;Zhang, Guo-Jun;Guo, Kun-Feng;Kong, Chui-Ze
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.521-525
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    • 2012
  • Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

A New Flavonol Glycoside from the Leaves of Boscia senegalensis

  • Morgan, Abubaker M.A.;Kim, Jang Hoon;Kim, Sang Kyum;Lim, Chi-Hwan;Kim, Young Ho
    • Bulletin of the Korean Chemical Society
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    • v.35 no.12
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    • pp.3447-3452
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    • 2014
  • Detailed chemical investigation of Boscia senegalensis (Per) Lam. ex Poir. led to the isolation of one new flavonol glycoside, rhamnocitrin-3-O-${\beta}$-$\small{D}$-(6"-O-E-feruloyl)-glucopyranoside named bosenegaloside A (1), with seven known compounds, rhamnocitrin-3-O-${\beta}$-$\small{D}$-(6"-O-E-p-coumaroyl)-glucopyranoside (2), rhamnocitrin-3-O-${\beta}$-$\small{D}$-glucopyranoside (3), 3,4,5-trimethoxyphenol-${\beta}$-$\small{D}$-glucopyrinoside (4), lasianthionoside A (5), 3,7-dimethyl-1-octene-3,6,7-triol-6-O-${\beta}$-$\small{D}$-glucopyranoside (6), syringin (7), and austroside B (8). The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The inhibitory activity of the isolated compounds on soluble epoxide hydrolase (sEH) was assessed. Compounds 1-3 potently inhibited sEH activity with $IC_{50}$ values of $12.8{\pm}0.5$, $18.4{\pm}0.2$, and $11.3{\pm}0.9{\mu}M$, respectively.

Batch Production of Chiral Epichlorohydrin by Enantioselective Hydrolysis Reaction using Rhodosporidium toruloides (Phodosporidium toruloides의 광학선택적 가수분해활성을 이용한 Chiral Epichlorohydrin의 회분식 생산)

  • 이은열;이재화
    • KSBB Journal
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    • v.19 no.1
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    • pp.38-41
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    • 2004
  • Enantioselective hydrolysis for the producing chiral epichlorohydrin from its racemic substrate was investigated using epoxide hydrolase activity of Rhodosporidium toruloides SJ-4. The effects of reaction parameters including pH, temperature, initial substrate concentration on initial hydrolysis rate and enantioselectivity were analyzed and optimized. The addition of detergent, Tween 20, enhanced the hydrolysis rate and enantioselectivity. Chiral (R)-epichlorohydrin with high optical purity (>99% ee) and yield of 25% (theoretically 50% maximum yield) was obtained from its racemate of 20 mM.

Identification of Soluble Epoxide Hydrolase Inhibitors from the Seeds of Passiflora edulis Cultivated in Vietnam

  • Cuong, To Dao;Anh, Hoang Thi Ngoc;Huong, Tran Thu;Khanh, Pham Ngoc;Ha, Vu Thi;Hung, Tran Manh;Kim, Young Ho;Cuong, Nguyen Manh
    • Natural Product Sciences
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    • v.25 no.4
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    • pp.348-353
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    • 2019
  • Soluble epoxide hydrolases (sEH) are enzymes present in all living organisms, metabolize epoxy fatty acids to 1,2-diols. sEH in the metabolism of polyunsaturated fatty acids plays a key role in inflammation. In addition, the endogenous lipid mediators in cardiovascular disease are also broken down to diols by the action of sEH that enhanced cardiovascular protection. In this study, sEH inhibitory guided fractionation led to the isolation of five phenolic compounds trans-resveratrol (1), trans-piceatannol (2), sulfuretin (3), (+)-balanophonin (4), and cassigarol E (5) from the ethanol extract of the seeds of Passiflora edulis Sims cultivated in Vietnam. The chemical structures of isolated compounds were determined by the interpretation of NMR spectral data, mass spectra, and comparison with data from the literature. The soluble epoxide hydrolase (sEH) inhibitory activity of isolated compounds was evaluated. Among them, trans-piceatannol (2) showed the most potent inhibitory activity on sEH with an IC50 value of 3.4 μM. This study marks the first time that sulfuretin (3) was isolated from Passiflora edulis as well as (+)-balanophonin (4), and cassigarol E (5) were isolated from Passiflora genus.

chemopreventive Effects of 2-(Allylthio) pyrazine

  • Kim, Nak-Doo;Kim, Sang-Geon
    • Archives of Pharmacal Research
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    • v.22 no.2
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    • pp.99-107
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    • 1999
  • A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.

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