Antioxidative activity of resveratrol and its derivatives isolated from seeds of Paeonia lactiflora

Seven stilbenes, a new cis-epsilon-viniferin and the six known stilbenes, trans-resveratrol, trans-resveratrol-4'-O-beta-D-glucopyranoside, trans-epsilon-viniferin, gnetin H, and suffruticosol A and B, were isolated and identified from seeds of Paeonia lactiflora. The antioxidative activity of these stilbene derivatives was evaluated against the 2-deoxyribose degradation and rat liver microsomal lipid peroxidation induced by the hydroxyl radical generated via a Fenton-type reaction. Among these stilbenes, trans-epsilon-viniferin and gnetin H significantly inhibited 2-deoxyribose degradation and lipid peroxidation in rat liver microsomes. In addition, cis-epsilon-viniferin, and suffruticosol A and B also exhibited moderate antioxidative activity. These results suggest that resveratrol dimers and trimers, together with resveratrol from seeds of Paeonia lactiflora may be useful as potential sources of natural antioxidants.     

The anti-biofilm and anti-virulence activities of trans-resveratrol and oxyresveratrol against uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections, which are one of the most common infectious disease types in humans. UPEC infections involve bacterial cell adhesion to bladder epithelial cells, and UPEC can also form biofilms on indwelling catheters that are often tolerant to common antibiotics. In this study, the anti-biofilm activities of t-stilbene, stilbestrol, t-resveratrol, oxyresveratrol, ε-viniferin, suffruticosol A, and vitisin A were investigated against UPEC. t-Resveratrol, oxyresveratrol, and ε-viniferin, suffruticosol A, and vitisin A significantly inhibited UPEC biofilm formation at subinhibitory concentrations (10–50?μg ml^?1). These findings were supported by observations that t-resveratrol and oxyresveratrol reduced fimbriae production and the swarming motility in UPEC. Furthermore, t-resveratrol and oxyresveratrol markedly diminished the hemagglutinating ability of UPEC, and enhanced UPEC killing by human whole blood. The findings show that t-resveratrol, oxyresveratrol, and resveratrol oligomers warrant further attention as antivirulence strategies against persistent UPEC infections.     

Cis ε-viniferin: A New Antifungal Resveratrol Dehydrodimer from Cyphostemma crotalarioides Roots

Six antifungal constituents were isolated from the roots of Cyphostemma crotalarioides (Vitaceae): a new product, Cis‐ε‐viniferin 3, along with five known compounds: trans‐resveratrol I and its oligomers: trans ε‐viniferin 2, gnetin C 4, pallidol 5 and gnetin E 6. It is the first time such compounds have been reported in this plant species. The roots tissues were found to be rich in other resveratrol oligomers, however, the available amounts of the other purified products did not allow structure investigations. No fungicidal activity was detected in the leaves of this plant.     

Stilbenoids from the stem of Gnetum latifolium (Gnetaceae)

An acetone extract of the stem of Gnetum latifolium Blume afforded the stilbene trimer (latifolol) together with five known stilbenoids (gnetin E, gnetin D, gnetin C, (-)epsilon -viniferin and resveratrol). Their structures were elucidated on the basis of spectral evidence, in particular by using 2D NMR methods.     

Contents of Resveratrol,Piceid, and Their Isomers in Commercially Available Wines Made from Grapes Cultivated in Japan

The presence of resveratrol (3,5,4′-trihydroxystilbene) and its β-glucoside, piceid (resveratrol-3-β-D-glucopyranoside), together with their isomers in wine appears to be one of the beneficial factors conferring a protective effect against cardiovascular disease through red wine ingestion. A total of 42 red and white wines was collected in arears from Hokkaido to Kyushu in Japan. The wines were fractionated with a C₁₈ Sep-pak cartridge, and the active principles were eluted with ethyl acetate. Crude trans- and cis-piceid were extracted from a Chinese medicine, ‘Kojohkon’ (Polygonum cuspidatum), and their retention times and UV absorption were confirmed by HPLC. trans- and cis-Resveratrol, and trans- and cis-piceid were analyzed in a short C₁₈ HPLC column, and cis-resveratrol was quantified from the amount of cis-isomer converted from authentic trans-resveratrol that had been treated by UV irradiation. The content of piceid is shown as the resveratrol equivalent. The average content of total stilbene compounds was 4.37mg/liter in red wines, while only 0.68 mg/liter in white wines. Red wines made from Pinot noir, Merlot, and Zweigeltrebe grapes all had a high resveratrol content.     

The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid

Abstract

The biomimetic model of micelles of linoleic acid containing 2-mercaptoethanol and the antioxidant was examined under gamma irradiation up to 400?Gy in aerobic or deoxygenated conditions where thiyl radicals are the main reactive species. Lipid peroxidation was retarded by ascorbic acid and α-tocopherol, whereas this process was strongly inhibited by resveratrol as effectively as the ascorbic acid/α-tocopherol mixture. Furthermore, antioxidants have a much stronger inhibitory effect on the peroxidation in the presence of 2-mercaptoethanol, and at the same time show protective properties of the double bond, decreasing the cis–trans isomerization. Under anaerobic conditions, cis–trans isomerization occurred and antioxidants efficiency increased along the series: resveratrol < α-tocopherol?<?ascorbic acid. This result is explained taking into account the double bond localization in the hydrophobic core of the micelle and the need of co-localization of the antioxidant in order to get an anti-isomerizing activity and protection of the natural lipid geometry.     

3,4,4′-Trihydroxy-trans-stilbene,an analogue of resveratrol,is a potent antioxidant and cytotoxic agent

Abstract

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a naturally occurring polyphenol widely distributed in food and dietary plants. This phytochemical has been intensively studied as an efficient antioxidant and anticancer agent, and a variety of substituted stilbenes have been developed in order to improve the potency of resveratrol. In this work, we described the synthesis of 3,4,4 -trihydroxy-trans-stilbene (3,4,4′-THS), an analogue of resveratrol, and studied its antioxidant and cytotoxic activity in vitro. 3,4,4 -THS was much more efficient than resveratrol in protecting against free radical-induced lipid peroxidation, photo-sensitized DNA oxidative damage, and free radical-induced hemolysis of human red blood cells. More potent growth inhibition in cultured human leukemia cells (HL-60) was also observed for 3,4,4 -THS. The relationship between the antioxidant efficiency and cytotoxic activity was discussed, with the emphasis on inhibition of the free radical enzyme ribonucleotide reductase by antioxidants. The result that this subtle structure modification of resveratrol drastically improves its bioactivity provides important strategy to develop novel resveratrol-based molecules.     

Biomarkers of lipid peroxidation in clinical material

Background

Free radical-mediated lipid peroxidation has been implicated in a number of human diseases. Diverse methods have been developed and applied to measure lipid peroxidation products as potential biomarkers to assess oxidative stress status in vivo, discover early indication of disease, diagnose progression of disease, and evaluate the effectiveness of drugs and antioxidants for treatment of disease and maintenance of health, respectively. However, standardized methods are not yet established.

Scope of review

Characteristics of various lipid peroxidation products as biomarkers are reviewed on the basis of mechanisms and dynamics of their formation and metabolism and also on the methods of measurement, with an emphasis on the advantages and limitations.

Major conclusions

Lipid hydroxides such as hydroxyoctadecadienoic acids (HODE), hydroxyeicosatetraenoic acids (HETE), and hydroxycholesterols may be recommended as reliable biomarkers. Notably, the four HODEs, 9-cis,trans, 9-trans,trans, 13-cis,trans, and 13-trans,trans-HODE, can be measured separately by LC–MS/MS and the trans,trans-forms are specific marker of free radical mediated lipid peroxidation. Further, isoprostanes and neuroprostanes are useful biomarker of lipid peroxidation. It is important to examine the distribution and temporal change of these biomarkers.

General significance

Despite the fact that lipid peroxidation products are non-specific biomarkers, they will enable to assess oxidative stress status, disease state, and effects of drugs and antioxidants. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.     

Microbial Resolution of Racemic 2- and 3-Alkylcyclohexanols

By using microorganisms (their esterase), (±)-trans and cis-2-methylcyclohexyl acetates were asymmetrically hydrolyzed to (?)-trans-2-methylcyc]ohexanol with (+)-trans-2-methyl-cyclohexyl acetate and (?)-cis-2-methylcyclohexanol with (+)-cis-2-methylcyclohexyl acetate. Similarly (±)-trans and cis-3-methylcyclohexyl acetates were hydrolyzed by the same microorganisms to give (+)-trans-3-methylcyclohexanol with (?)-trans-3-methylcyclohexyl acetate and (?)-cis-3-methylcyclohexanol with (+)-cis-3-methylcyclohexyl acetate.     

A Common Structure of Substrate Shared by Lignostilbenedioxygenase Isozymes from Sphingomonas paucimobilis TMY1009

A common structure of substrates of lignostilbenedioxygenases was investigated using synthesized stilbenes. Cell-free extracts of Sphingomonas paucimobilis TMY1009 degraded only trans-4-hydroxystilbene and trans-4-hydroxy-3-methoxystilbene. Other stilbenes that had no 4-hydroxyl group and had a cis structure were not substrates for lignostilbenedioxygenases. These results indicate that a 4-hydroxyl group and trans-structure is necessary for the common structure for substrates of lignostilbenedioxygenases.     

Microbial Allyl Rearrangement and Resolution of Acetates of Unsaturated Cyclic Terpene Alchols by Pseudomonas sp. NOF-5 Strain

Microbial hydrolysis of the acetates of unsaturated cyclic terpene alcohols by Pseudomonas sp. NOF-5 isolated from soil was investigated. (±)-trans-Carveyl acetate ((±)-trans-3) was enantio-selectively hydrolyzed with NOF-5 strain to give ( – )-trans-carveol (( – )-trans-2 of 86.6% optical purity). However, the hydrolysis of (±)-cis-3 was less enantioselective, while (±)-piperitylacetate ((±)-6, a cis and trans mixture) was hydrolyzed to give the ( – )-trans- and ( – )-cis-piperitols (( – )- trans-5 and ( – )-cis-5) in a poor optical yield. In this case, other tert-alcohols, ( + )-trans- and ( – )- ds-2-p-menthen-1-ols ((±)-trans-7 and ( – )-cis-7), were also produced. Furthermore, microbial and enzymic allyl rearrangements of ( + )-trans-6 and ( – )-trans-verbenylacetate (( – )-trans-11) were studied. Biological treatment of (+)-trans-6 and ( – )-trans-11 with NOF-5 or its esterase gave (+)-trans- and (-)-cis-1 and ( + )-cis-3-pinen-2-ol (( + )-cis-12), respectively.     

Galloylated catechins and stilbene diglucosides in Vitis vinifera cell suspension cultures

Suspension cultures of Vitis vinifera were found to produce catechins and stilbenes. When cells were grown in a medium inducing polyphenol synthesis, (−)-epicatechin-3-O-gallate, dimeric procyanidin B-2 3′-O-gallate and two resveratrol diglucosides were isolated, together with a new natural compound that was identified as cis-resveratrol-3,4′-O-β-diglucoside by spectroscopical methods.     

Quantification of retinyl-β-glucuronides in rat urine by reversed-phase high-performance liquid chromatography with ultraviolet detection

A method is presented for the quantitation of the glucuronide conjugates of 4-oxo-all-trans-, 4-oxo-13-cis-, 13-cis-, 9-cis- and all-trans-retinoic acids in rat urine utilizing solid-phase extraction and gradient reversed-phase HPLC. The range of the R.S.D. (relative standard deviation) for both the inter- and intra-assay precision was 1.45,2–11.60%. The recovery of all retinoyl-β-glucuronides from rat urine ranged between 89 and 99%. The limit of detection was 0.01 μg/ml using 5 ml of rat urine. This method was applied to quantitate the amount of retinoyl-β-glucuronides produced in urine after the single and multiple oral administrations of 13-cis-, 9-cis- and all-trans-retinoic acids to rats.     

Modulation of lipid droplet size and lipid droplet proteins by trans-10,cis-12 conjugated linoleic acid parallels improvements in hepatic steatosis in obese,insulin-resistant rats

The isomer-specific effects of conjugated linoleic acid (CLA) on hepatic steatosis were assessed in fa/fa Zucker rats, a model for insulin resistance and the metabolic syndrome. Eight weeks of feeding trans-10,cis-12 CLA significantly improved glucose tolerance without changing body weight or visceral adipose mass. The trans-10,cis-12 isomer was also associated with reduced liver lipid content, improved liver function and reduced inflammation; these effects were not observed in rats fed the cis-9,trans-11 CLA isomer. Reduced liver lipid content did not correlate with activation of AMP-activated protein kinase or suppressed activation of sterol-regulatory element binding protein-1, two key regulators of hepatic lipid metabolism. Interestingly, rats fed cis-9,trans-11 CLA had fewer cytoplasmic lipid droplets in hepatocytes compared to rats fed control diet, but these droplets were larger in size. Conversely, fa/fa rats fed the trans-10,cis-12 CLA isomer had greater numbers of hepatic lipid droplets that were smaller in size, resulting in overall lower total lipid within these droplets. Changes in lipid droplets were associated with lower hepatic levels of PERILIPIN-2 (formerly known as adipophilin) in rats fed trans-10,cis-12 CLA, whereas amounts of other members of the PERILIPIN family of lipid droplet proteins were unaffected by dietary CLA. However, CLA isomers differentially affected the subcellular localization of these proteins. Treatment of H4IIE rat hepatoma cells with CLA isomers neither prevented nor reversed, but rather induced cytoplasmic lipid droplet formation, suggesting that the anti-steatotic effects of trans-10,cis-12 CLA are likely indirect and potentially mediated via increased lipid utilization by peripheral tissues.     

Minor Constituents of Japanese Ho-Leaf Oil

The main component of Japanese Ho-leaf oil has been shown to be (?)-linalool (80~90%), and the following twenty minor constituents newly have been identified; methyl vinyl ketone, methyl isobutyl ketone, mesityl oxide, β-pinene, myrcene, (+)-limonene, cis- and trans-ocimene, n-hexanol, cis-3-hexenol, cis- and trans-linalool oxide, (?)-1-terpinen-4-ol, (+)-cis and (+)-trans-2,6,6-trimethyl-2-vinyl-5-hydroxytetrahydropyran, citronellol, nerol, (+)-β-selinene, (+)-tagetonol and (?)-trans-hotrienol. (+)-Tagetonol and (?)-trans-hotrienol have been demonstrated to be (+)-3,7-dimethyl-3-hydroxy-1-octen-5-one (III) and (3R)-(?)-trans-3,7-dimethyl-3-hydroxy-1,5,7-octatriene (IX), respectively.     

Simultaneous determination of all-trans-, 13-cis- and 9-cis-retinoic acid, their 4-oxo metabolites and all-trans-retinol in human plasma by high-performance liquid chromatography

All-trans-retinoic acid (all-trans-RA) and 13-cis-retinoic acid (13-cis-RA), due to their effects on cell differentiation, proliferation and angiogenesis, improved treatment results in some malignancies. Pharmacokinetic studies of all-trans-RA and 13-cis-RA along with monitoring of retinoic acid metabolites may help to optimize retinoic acid therapy and to develop new effective strategies for the use of retinoic acids in cancer treatment. Therefore, we developed a HPLC method for the simultaneous determination in human plasma of the physiologically important retinoic acid isomers, all-trans-, 13-cis- and 9-cis-retinoic acid, their 4-oxo metabolites, 13-cis-4-oxoretinoic acid (13-cis-4-oxo-RA) and all-trans-4-oxoretinoic acid (all-trans-4-oxo-RA), and vitamin A (all-trans-retinol). Analysis performed on a silica gel column with UV detection at 350 nm using a binary multistep gradient composed on n-hexane, 2-propanolol and glacial acetic acid. For liquid-liquid extraction a mixture of n-hexane, dichloromethane and 2-propanolol was used. The limits of detection were 0.5 ng/ml for retinoic acids and 10 ng/ml for all-trans-retinol. The method showed good reproducibility for all components (within-day C.V.: 3.02–11.70%; day-to-day C.V.: 0.01–11.34%. Furthermore, 9-cis-4-oxoretinoic acid (9-cis-4-oxo-RA) is separated from all-trans-4-oxo-RA and 13-cis-4-oxo-RA. In case of clinical use of 9-cis-retinoic acid (9-cis-RA) the pharmacokinetics and metabolism of this retinoic acid isomer can also be examined.     

Production of trans-10, cis-12 Conjugated Linoleic Acid in Rice

Conjugated linoleic acid (CLA) has anti-carcinogenic and anti-atherosclerosis activity, and modulatory effects on the immune system and lipid metabolism. To produce a transgenic rice plant that can accumulate CLA, a linoleate isomerase gene that can convert linoleic acid to trans-10, cis-12 CLA was introduced and expressed under the control of seed-specific promoters from the oleosin and globulin genes. The fatty acid composition of the transgenic rice grain was analyzed by gas chromatography. Although there was no clear difference in the fatty acid composition between seeds from transformed versus untransformed plants, a peak of trans-10, cis-12 CLA methyl ester, which was not present in seeds from untransformed plants, was found in transformed plants. The trans-10, cis-12 CLA comprised an average of 1.3% (w/w) of the total fatty acids in seeds carrying the oleosin promoter in comparison to 0.01% (w/w) in seeds carrying the globulin promoter. In addition, approximately 70 and 28% of the total amount of the CLA isomer were present in the triacylglycerol and free fatty acid fractions, respectively. These results demonstrate the ability to produce fatty acid components of vegetable oils with novel physiological activities in crops.     

Simultaneous quantification of retinol, retinal, and retinoic acid isomers by high-performance liquid chromatography with a simple gradiation

A new method of high-performance liquid chromatography (HPLC) analysis to quantify isomers of retinol, retinal and retinoic acid simultaneously was established. The HPLC system consisted of a silica gel absorption column and a linear gradient with two kinds of solvents containing n-Hexane, 2-propanol, and glacial acetic acid in different ratios. It separated six retinoic acid isomers (13-cis, 9-cis, all-trans, all-trans-4-oxo, 9-cis-4-oxo, 13-cis-4-oxo), three retinal isomers (13-cis-, 9-cis-, and all-trans) and two retinol isomers (13-cis- and all-trans). Human serum samples were subjected to this HPLC analysis and at least, all-trans retinol, 13-cis retinol, and all-trans retinoic acid were detectable. This HPLC system is useful for evaluating retinoic acid formation from retinol via a two-step oxidation pathway. Moreover, it could be applied to monitoring the concentrations of various retinoids, including all-trans retinoic acid in human sera.     

Enzymatic Formation of Hexadecenoic Acid from Palmitic Acid

Desaturation of palmitic acid was investigated in an enzyme system prepared from rat liver. 2-trans-Hexadecenoic acid as well as 9-cis-hexadecenoic acid (palmitoleic acid) were found to be formed as monoenoic acid in this system.