Browse
Submit Data
Databases
API
Help

Dataset Information

36 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Soluble Epoxide Hydrolase Inhibitory Activity of Components Isolated from Apios americana Medik.

ABSTRACT: A new compound 1, 5-methoxy-2,5,7,4'-tetrahydroxy-coumaronochromone, along with seven known compounds (2-8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 ?M. The respective competitive (1) and mixed (2) inhibitors were revealed to have Ki values of 21.0 ± 0.8 and 14.5 ± 1.5 ?M, based on the Dixon plot. The potential inhibitor (2) was visually presented in a predicted binding pose in the receptor by molecular docking. Additionally, molecular dynamics were performed for a detailed understanding of their complex by Gromacs 4.6.5 package.

SUBMITTER: Kim JH

PROVIDER: S-EPMC6151598 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Soluble Epoxide Hydrolase Inhibitory Activity of Components Isolated from Apios americana Medik.

Kim Jang Hoon JH Kim Hyo Young HY Kang Si Yong SY Kim Young Ho YH Jin Chang Hyun CH

Molecules (Basel, Switzerland) 20170830 9

A new compound 1, 5-methoxy-2,5,7,4'-tetrahydroxy-coumaronochromone, along with seven known compounds (2-8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 μM. The respective competitive (1) and mixed (2) inh ...[more]

PMID: 28867792

Similar Datasets

Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase.

Project description:The quaternary isoquinoline alkaloids of palmatine (1), berberine (2), and jatrorrhizine (3) were evaluated in terms of their ability to inhibit soluble epoxide hydrolase (sEH). They had similar inhibitory activities, with IC50 values of 29.6 ± 0.5, 33.4 ± 0.8, and 27.3 ± 0.4 μM, respectively. Their respective Ki values of 26.9, 46.8, and 44.5 μM-determined by enzyme kinetics-indicated that they inhibited the catalytic reaction by binding noncompetitively with sEH. The application of computational chemistry to the in vitro results revealed the site of the receptor to which the ligand would likely bind. Accordingly, three alkaloids were identified as having a suitable basic skeleton for lead compound development of sEH inhibitors.

| S-EPMC9498296 | biostudies-literature

Chemical Constituents from Apios americana and Their Inhibitory Activity on Tyrosinase.

Project description:The goal of this study was to identify phytochemicals with inhibitory activity against tyrosinase. Nine compounds 1-9 were isolated from the tubers of Apios americana. This is the first report of aromadendrin 5-methyl ether (1) being isolated from the Apios species. Among them, compounds 2 and 8 showed inhibitory activity toward tyrosinase. Based on a Dixon plot, the potential Ki values of competitive inhibitors 2 and 8 were calculated as 10.3 ± 0.8 µM and 44.2 ± 1.7 µM, respectively. An IC50 value of 13.2 ± 1.0 µM was calculated for the slow-binding inhibitor 2 after preincubation with tyrosinase. Additionally, the predicted binding sites between the receptor and ligand, as well as secondary structure changes, in the presence of 2 were examined by molecular simulation.

| S-EPMC6017567 | biostudies-literature

Soluble Epoxide Hydrolase Inhibitory Activity of Selaginellin Derivatives from Selaginella tamariscina.

Project description:Selaginellin derivatives 1-3 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH) to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (1-3) inhibited sEH enzymatic activity and PHOME hydrolysis, in a dose-dependent manner, with IC50 values of 3.1 ± 0.1, 8.2 ± 2.2, and 4.2 ± 0.2 ?M, respectively. We further determined that the derivatives function as non-competitive inhibitors. Moreover, the predicted that binding sites and interaction between 1-3 and sEH were solved by docking simulations. According to quantitative analysis, 1-3 were confirmed to have high content in the roots of S. tamariscina; among them, selaginellin 3 exhibited the highest content of 189.3 ± 0.0 ?g/g.

| S-EPMC6331899 | biostudies-literature

Inhibitory activity of lignanamides isolated from hemp seed hulls(Cannabis sativa L.) against soluble epoxide hydrolase.

Project description:Soluble epoxide hydrolase (sEH) is a therapeutic target for inflammation. In the present study, we isolated one new (1) and four known (2-5) compounds from the ethyl acetate fraction of hemp seed hulls. Their structures were elucidated as lignanamides via nuclear magnetic resonance and mass spectral analyses. All five compounds inhibited sEH activity, with half-maximal inhibitory concentrations of 2.7 ± 0.3 to 18.3 ± 1.0 μM. These lignanamides showed a competitive mechanism of inhibition via binding to sEH, with ki values below 10 μmol. Molecular simulations revealed that compounds 1-5 fit stably into the active site of sEH, and the key amino acid residues participating in their bonds were identified. It was confirmed that the potential inhibitors 4 and 5 continuously maintained a distance of 3.5 Å from one (Tyr383) and four amino (Asp335, Tyr383, Asn472, tyr516) residues, respectively. These findings provide a framework for the development of naturally derived sEH inhibitors.

| S-EPMC10559049 | biostudies-literature

Soluble epoxide hydrolase dimerization is required for hydrolase activity.

Project description:Soluble epoxide hydrolase (sEH) plays a key role in the metabolic conversion of the protective eicosanoid 14,15-epoxyeicosatrienoic acid to 14,15-dihydroxyeicosatrienoic acid. Accordingly, inhibition of sEH hydrolase activity has been shown to be beneficial in multiple models of cardiovascular diseases, thus identifying sEH as a valuable therapeutic target. Recently, a common human polymorphism (R287Q) was identified that reduces sEH hydrolase activity and is localized to the dimerization interface of the protein, suggesting a relationship between sEH dimerization and activity. To directly test the hypothesis that dimerization is essential for the proper function of sEH, we generated mutations within the sEH protein that would either disrupt or stabilize dimerization. We quantified the dimerization state of each mutant using a split firefly luciferase protein fragment-assisted complementation system. The hydrolase activity of each mutant was determined using a fluorescence-based substrate conversion assay. We found that mutations that disrupted dimerization also eliminated hydrolase enzymatic activity. In contrast, a mutation that stabilized dimerization restored hydrolase activity. Finally, we investigated the kinetics of sEH dimerization and found that the human R287Q polymorphism was metastable and capable of swapping dimer partners faster than the WT enzyme. These results indicate that dimerization is required for sEH hydrolase activity. Disrupting sEH dimerization may therefore serve as a novel therapeutic strategy for reducing sEH hydrolase activity.

| S-EPMC3597810 | biostudies-literature

Sorafenib has soluble epoxide hydrolase inhibitory activity, which contributes to its effect profile in vivo.

Project description:The advent of multikinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor has revolutionized the treatment of highly angiogenic malignancies such as renal cell carcinoma. Interestingly, several such inhibitors are commercially available, and they each possess diverse specific beneficial and adverse effect profiles. In examining the structure of sorafenib, it was hypothesized that this compound would possess inhibitory effects on the soluble epoxide hydrolase, an enzyme with pleiotropic effects on inflammation and vascular disease. We now show that sorafenib but not another VEGF receptor targeted inhibitor sunitinib is a potent inhibitor of the human soluble epoxide hydrolase in vitro (K(I) = 17 +/- 4 nmol/L). Furthermore, sorafenib causes the expected in vivo shift in oxylipid profile resulting from soluble epoxide hydrolase inhibition, evidence of a reduction in the acute inflammatory response. Lipopolysaccharide-induced hypotension was reversed with sorafenib but not sunitinib treatment, suggesting that soluble epoxide hydrolase inhibition accounts for at least part of the anti-inflammatory effect of sorafenib. The pharmacokinetic studies presented here in light of the known potency of sorafenib as a soluble epoxide hydrolase inhibitor indicate that the soluble epoxide hydrolase will be largely inhibited at therapeutic doses of sorafenib. Thus, it is likely that soluble epoxide hydrolase inhibition contributes to the beneficial effects from the inhibition of the VEGF receptor and other kinases during treatment with sorafenib.

| S-EPMC2728155 | biostudies-literature

Coumarin and Moracin Derivatives from Mulberry Leaves (Morus alba L.) with Soluble Epoxide Hydrolase Inhibitory Activity.

Project description:This study identified three coumarins (1-3), and six moracin derivatives (4-9). The structures of these natural compounds were determined by the spectroscopic methods, including 1D and 2D NMR methods, and comparison with previous reported data. All of the isolated compounds were assessed for the effects on the soluble epoxide hydrolase (sEH) inhibitory activity. Among them, compounds 1-7 exhibited significant inhibitory effect with 100% inhibitory, with IC50 values of 6.9, 0.2, 15.9, 1.1, 1.2, 9.9, and 7.7 µM, respectively. A kinetic study revealed that compounds 1-4, and 6 were competitive types of inhibitors, compounds 5 and 7 were mixed types of inhibitors. These results suggest that moracin and coumarin derivatives from mulberry leaves are significant sEH inhibitors.

| S-EPMC7504814 | biostudies-literature

Proton shuttles and phosphatase activity in soluble epoxide hydrolase.

Project description:Recently, a novel metal Mg2+-dependent phosphatase activity has been discovered in the N-terminal domain of the soluble epoxide hydrolase (sEH), opening a new branch of fatty acid metabolism and providing an additional site for drug targeting. Importantly, the sEH N-terminal fold belongs to the haloacid dehalogenase (HAD) superfamily, which comprises a vast majority of phosphotransferases. Herein, we present the results of a computational study of the sEH phosphatase activity, which includes classical molecular dynamics (MD) simulations and mixed quantum mechanical/molecular mechanics (QM/MM) calculations. On the basis of experimental results, a two-step mechanism has been proposed and herein investigated: (1) phosphoenzyme intermediate formation and (2) phosphoenzyme intermediate hydrolysis. Building on our earlier work, we now provide a detailed description of the reaction mechanism for the whole catalytic cycle along with its free energy profile. The present computations suggest metaphosphate-like transition states for these phosphoryl transfers. They also reveal that the enzyme promotes water deprotonation and facilitates shuttling of protons via a metal-ligand connecting water bridge (WB). These WB-mediated proton shuttles are crucial for the activation of the solvent nucleophile and for the stabilization of the leaving group. Moreover, due to the conservation of structural features in the N-terminal catalytic site of sEH and other members of the HAD superfamily, we suggest a generalization of our findings to these other metal-dependent phosphatases.

| S-EPMC2533064 | biostudies-literature

Inhibitory Activity of Flavonoids, Chrysoeriol and Luteolin-7-O-Glucopyranoside, on Soluble Epoxide Hydrolase from Capsicum chinense.

Project description:: Three flavonoids derived from the leaves of Capsicum chinense Jacq. were identified as chrysoeriol (1), luteolin-7-O-glucopyranoside (2), and isorhamnetin-7-O-glucopyranoside (3). They had IC50 values of 11.6±2.9, 14.4±1.5, and 42.7±3.5 µg/mL against soluble epoxide hydrolase (sEH), respectively. The three inhibitors (1-3) were found to non-competitively bind into the allosteric site of the enzyme with Ki values of 10.5±3.2, 11.9 ±2.8 and 38.0±4.1 µg/mL, respectively. The potential inhibitors 1 and 2 were located at the left edge ofa U-tube shape that contained the enzyme active site. Additionally, we observed changes in several factors involved in the binding of these complexes under 300 K and 1 bar. Finally, it was confirmed that each inhibitor, 1 and 2, could be complexed with sEH by the "induced fit" and "lock-and-key" models.

| S-EPMC7072517 | biostudies-literature

Assessment of soluble epoxide hydrolase activity in vivo: A metabolomic approach.

Project description:Soluble epoxide hydrolase (sEH) converts several FFA epoxides to corresponding diols. As many as 15 FFA epoxide-diol ratios are measured to infer sEH activity from their ratios. Using previous data, we assessed if individual epoxide-diol ratios all behave similarly to reflect changes in sEH activity, and whether analyzing these ratios together increases the power to detect changes in in-vivo sEH activity. We demonstrated that epoxide-diol ratios correlated strongly with each other (P < 0.05), suggesting these ratios all reflect changes in sEH activity. Furthermore, we developed a modeling approach to analyze all epoxide-diol ratios simultaneously to infer global sEH activity, named SAMI (Simultaneous Analysis of Multiple Indices). SAMI improved power in detecting changes in sEH activity in animals and humans when compared to individual ratio estimates. Thus, we introduce a new powerful method to infer sEH activity by combining metabolomic determination and simultaneous analysis of all measurable epoxide-diol pairs.

| S-EPMC7237305 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data