Lipid Peroxidation In Liver Microsomes Research Articles

The Systematic Assessment of the Membrane-Stabilizing and Antioxidant Activities of Several Kazakhstani Plants in the Asteraceae Family.

The objective of our research was to examine the antioxidant and membrane-protective characteristics of a few medicinal plant extracts belonging to the Asteracea family, along with their flavonoid and polyphenolic content, in order to identify strategies for enhancing beverage composition and boosting the antioxidant capacity of green and black tea. The activity of aqueous-ethanolic extracts from the dried parts of plants, such as Arictum tomentosum Mill., Ghnapilum kasachstanicum Kirp. & Kuprian. ex Kirp., Artemisia schrenkiana Ledeb., A. rutifolia Steph. ex Spreng., A. cina O.Berg, and A. vulgaris L., were examined using a model of Wistar rats. Thiobarbituric acid-reacting substances (TBARS), a marker of malondialdehyde concentration, were used to measure the amount of lipid peroxidation (LPO) in liver microsomes. Considering the outcomes, the extracts from A. tomentosum, G. kasachstanicum, and A. vulgaris exhibit the strongest membrane-stabilizing action among those examined. At a concentration of 5 g/mL, the extracts of these plants demonstrated a significant anti-hemolitic impact, whereas the remaining extracts displayed a similar effect at doses above 10 g/mL. Accordingly, among the extracts studied, the A. tomentosum, G. kasachstanicum, A. schrenkiana, A. rutifolia, A. cina, and A. vulgaris extracts have significant antioxidant properties. The integrated antioxidant and antihemolytic qualities of A. tomentosum and green tea extracts were comparable to those of the individual plant extracts. When the extracts of A. schrenkiana and green tea were combined, similar outcomes were seen, suggesting that there was no appreciable synergistic interaction.

A new lignan glucoside from stems and branches of Rhododendron ovatum

Ten lignans were isolated from the ethanol extract of stems and branches of Rhododendron ovatum through column chromatography over silica gel, ODS, Sephadex LH-20, and MCI-gel resin and semi-preparative RP-HPLC. The structures of all compounds were elucidated by extensive spectroscopic data analysis(UV, IR, HR-ESI-MS, ECD and NMR) as(-)-4-epi-lyoniresinol-9'-O-α-L-rhamnopyranoside(1),(+)-lyoniresinol-3α-O-α-L-rhamnopyranoside(2),(+)-5'-methoxyisolariciresinol-9'-O-α-L-rhamnopyranoside(3),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(4),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(5),(-)-4-epi-lyoniresinol-9'-O-β-D-glucopyransoide(6), racemiside(7), neociwujiaphenol(8),(+)-syringaresinol(9), and homohesperitin(10). Among them, compound 1 was a new aryltetralin-type lignan. All the isolated lignans were tested for antioxidant activities in Fe~(2+)-cysteine induced rat liver microsomal lipid peroxidation in vitro, and compounds 8 and 9 showed antioxidant activities on the formation of malondiadehyde(MDA) in rat liver microsomes at 1×10~(-5) mol·L~(-1), with significant inhibitory rates of 75.20% and 91.12%, respectively.

New iridal-type triterpenoid analogues with 6/5/6-fused carbon skeleton from the rhizomes of Belamcanda chinensis

Five new iridal-type triterpenoid derivatives with 6/5/6 tricyclic ring skeleton (1–5) were obtained from the rhizomes of Belamcanda chinensis. Their structures were determined on the basis of detailed spectroscopic data and ECD calculation. Compounds 1–5 possessed the same 6/5/6-fused carbon skeleton as Belamchinenin A, which further enriched this kind of iridals. In vitro bioassay, compounds 2 and 3 exhibited 51.95 and 54.52% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 μM. A putative biogenetic pathway for compounds 1–5 was proposed.

Long-chain fatty acid acylated derivatives of isoflavone glycosides from the rhizomes of Iris domestica

Six undescribed long-chain fatty acid esters of isoflavone glycosides were obtained from the rhizomes of Iris domestica (L.). Their structures were elucidated by comprehensive spectroscopic data, alkaline hydrolysis, and acid hydrolysis. This is the first report of the long-chain (C14–C18) fatty acid derivatives of isoflavone glycosides from natural products. Belamcandnoate B and D exhibited moderate cytotoxic activities against HCT-116, HepG2, and BGC823 cell lines with IC50 values of 1.69–6.86 μM. Belamcandnoate B and E exhibited 72.27 and 58.98% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 μM.

Evaluation of the Free Radical Scavenging Activities of Ellagic Acid and Ellagic Acid Peracetate by EPR Spectrometry.

The purpose of this study was to examine the free radical scavenging and antioxidant activities of ellagic acid (EA) and ellagic acid peracetate (EAPA) by measuring their reactions with the radicals, 2,2-diphenyl-1-picrylhydrazyl and galvinoxyl using EPR spectroscopy. We have also evaluated the influence of EA and EAPA on the ROS production in L-6 myoblasts and rat liver microsomal lipid peroxidation catalyzed by NADPH. The results obtained clearly indicated that EA has tremendous ability to scavenge free radicals, even at concentration of 1 µM. Interestingly even in the absence of esterase, EAPA, the acetylated product of EA, was also found to be a good scavenger but at a relatively slower rate. Kinetic studies revealed that both EA and EAPA have ability to scavenge free radicals at the concentrations of 1 µM over extended periods of time. In cellular systems, EA and EAPA were found to have similar potentials for the inhibition of ROS production in L-6 myoblasts and NADPH-dependent catalyzed microsomal lipid peroxidation.

Systematic Analysis of Combined Antioxidant and Membrane-Stabilizing Properties of Several Lamiaceae Family Kazakhstani Plants for Potential Production of Tea Beverages.

One of the most important compounds that exhibit a wide range of biological activities with especially strong antioxidant action are plant polyphenols. In the course of the experiment, the dose-dependent effects of polyphenols-rich extracts isolated from the Lamiaceae family Kazakhstani plants were studied on the processes of lipid peroxidation and on the degree of erythrocytes hemolysis. The activity of aqueous-ethanolic extracts from dried parts of plants, such as Origanum vulgare, Ziziphora bungeana, Dracocephalum integrifolium, Mentha piperita, Leonurus turkestanicus, Thymus serpyllum, and Salvia officinalis, was studied in a Wistar rat model. Lipid peroxidation (LPO) in liver microsomes was assessed by measuring malondialdehyde content in the form of thiobarbituric acid-reacting substances (TBARS). Estimation of osmotic resistance of isolated erythrocytes was evaluated based on hemoglobin absorbance. The amount of total phenolics in the extracts was measured using the Folin-Ciocalteu reagent method. Based on the results, Thymus serpyllum extract exhibited a significantly higher antioxidant activity (IC50 = 3.3 ± 0.7) compared to other plant extracts. Accordingly, among the extracts studied, those from Salvia officinalis, Thymus serpyllum, and Origanum vulgare show the most pronounced membrane-stabilizing activity. Antioxidant and antihemolytic properties of green tea and Origanum vulgare extract mixtures were similar to that of each individual plant extract. Similar results were obtained when the green tea extract was mixed with Mentha piperita, Ziziphora bungeana, and Dracocephalum integrifolium extracts, indicating no discernible synergistic interaction.

Sulfated Metabolites of Luteolin, Myricetin, and Ampelopsin: Chemoenzymatic Preparation and Biophysical Properties.

Authentic standards of food flavonoids are important for human metabolic studies. Their isolation from biological materials is impracticable; however, they can be prepared in vitro. Twelve sulfated metabolites of luteolin, myricetin, and ampelopsin were obtained with arylsulfotransferase from Desulfitobacterium hafniense and fully characterized by high-performance liquid chromatography, MS, and NMR. The compounds were tested for their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and N,N-dimethyl-p-phenylenediamine radicals, to reduce ferric ions and Folin-Ciocalteu reagent, and to inhibit tert-butyl hydroperoxide-induced lipid peroxidation of rat liver microsomes. The activity differed considerably even between monosulfate isomers. The parent compounds and myricetin-3'-O-sulfate were the most active while other compounds displayed significantly lower activity, particularly luteolin sulfates. No mutagenic activity of the parent compounds and their main metabolites was observed; only myricetin showed minor pro-mutagenicity. The prepared sulfated metabolites are now available as authentic standards for future in vitro and in vivo metabolic studies.

Six new monacolin analogs from red yeast rice.

Six novel monacolin analogs, monacolins V1-V6 (1-6), together with seven known ones (7-13), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods, especially 2D NMR (1H-1HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation. Monacolins V2 (2) and V3 (3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide (LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.

Eight new triterpenoid saponins with antioxidant activity from the roots of Glycyrrhiza uralensis Fisch

Eight new triterpenoid saponins (1–8), were isolated from the roots of Glycyrrhiza uralensis Fisch., together with 10 known triterpenoid saponins (9–18). Their structures were determined by analysis of their spectroscopic data and comparison with the reference. All of the compounds were evaluated for their antioxidant effects in the in vitro assay. Compounds 2 and 8 showed significant antioxidant activities against Fe2+/cysteine-induced liver microsomal lipid peroxidation at 0.1 μM.

A comparative study of phenolic compound antioxidant activity by the polarography method, using microsomal lipid peroxidation in vitro

Abstract For comparative purposes, a quantitative estimation of antioxidant activity of phenolic compounds of different classes was conducted by way of the polarography method, via the ADP-Fe2+ model of the induced ascorbate-dependent lipid peroxidation of rat liver micro-somes within an in-vitro system. As a result, it was recognized that the antioxidant properties of phenolic compounds depend on the nature and chemical structure of several substances. In respect of such activity, leaders in the classes of investigated polyphenolic compounds are: Propyl gallate = Gallotannin (Phenolcarboxylic acids and their derivatives) > Quercetin = Myricetin (Flavonols) > Luteolin (Flavo n) = Mangiferin (Xanthones) > Kaempferol (Flavonols) = Catechin (Flavans). Thus, the assessment of the inhibition ability of the lipid peroxidation of microsomes by phenolic compounds can be used as an accessible test for the preliminary quantitative estimation of their antioxidant properties.

Effect of Caesalpinia pulcherrima (L.) Sw. seeds on serum glucose and other metabolic parameters of normal and alloxan - induced diabetic rats

Oral administration of the ethanol extract of Caesalpinia pulcherrima seeds (CP - 250 and 500 mg/kg) caused significant fall in blood glucose levels even at 2½ h after a single dose of treatment in normal fasted and glucose loaded Wistar rats. At 250 mg/kg dose level, CP completely prevented the elevation of blood glucose caused by oral glucose feeding. In alloxan diabetic rats, CP was able to lower the blood glucose level to around 132 mg / 100 ml from 10th day and thereafter. The biochemical findings were supported by histopathological studies of liver, kidney and pancreas of control and treated rats. CP was able to increase catalase levels of diabetic rats. Reduced levels of serum protein and elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase(SGPT), alkaline phosphatase(ALP), cholesterol, triglycerides, creatinine and uric acid were almost normalised in CP treated diabetic rats. CP was also able to reduce in vitro lipid peroxidation in rat liver microsomes and inhibit 1- diphenyl – 2-picryl hydrazyl (DPPH) induced free radicals significantly.

Isolation and Purification of Galloyl, Caffeoyl, and Hexahydroxydiphenoyl Esters of Glucoses from Balanophora simaoensis by High-Speed Countercurrent Chromatography and Their Antioxidant Activities In Vitro.

High-speed counter-current chromatography was used to separate and purify galloyl, caffeoyl, and hexahydroxydiphenoyl esters of glucoses from the aerial parts of the parasitic plant Balanophora simaoensis for the first time using n-hexane-ethyl acetate-methanol-water (1:2:1:2, v/v) as the optimum solvent system. Accordingly, 1-O-(E)-caffeoyl-3-O-galloyl-β-d-glucopyranose (I, 12.5 mg), 1-O-(E)-caffeoyl-3-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-β-d-glucopyranose (II, 27.2 mg), and 1-O-(E)-caffeoyl-4,6-(S)-hexahydroxydiphenoyl-β-d-glucopyranose (III, 52.8 mg) with 98.0%, 98.5%, and 98.7% purities, respectively, were purified from 210 mg crude extract of B. simaoensis in a one-step separation. The structures of the glucose esters were identified by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance spectra (NMR). Their antioxidant activities were evaluated by measuring their inhibition activity on liver microsomal lipid peroxidation induced by the Fe2+-Cys system in vitro. Compounds I–III showed significant antioxidant activities with IC50 values ranging from 2.51 to 6.68 μm, respectively.

Selenium and sulphur derivatives of hydroxytyrosol: inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats.

The objective of this study was to evaluate the capacity of modified phenols synthesized from hydroxytyrosol, a natural olive oil phenol, specifically those containing a selenium or sulphur group, to inhibit lipid peroxidation. The compounds' abilities to inhibit lipid peroxidation in liver microsomes obtained from vitamin E-deficient rats were compared to hydroxytyrosol. All synthetic compounds had a significant higher ability to inhibit lipid peroxidation than hydroxytyrosol. Selenium derivates displayed a higher antioxidant activity than sulphur derivatives. In addition, the antioxidant activity increased with a higher number of heteroatoms in the hydroxytyrosol molecular structure. The study shows, for the first time, the ability of synthetic compounds, derived from the most active phenol present in olives in free form (hydroxytyrosol), and containing one or two atoms of sulphur or selenium, to inhibit the lipid peroxidation of vitamin E-deficient microsomes. The antioxidant activity of five thioureas, a disulfide, a thiol, three selenoureas, a diselenide, and a selenonium were evaluated and the results showed a higher inhibition of lipid peroxidation than the natural phenol. Selenium and sulphur derivatives of hydroxytyrosol are novel antioxidants with the potential to supplement the lack of vitamin E in the diet as natural alternatives for the prevention of diseases related to oxidative damage.

Hepatoprotective glycosides from the rhizomes of Imperata cylindrical

Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8–4′-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 μM) exhibited pronounced hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays. Furthermore, their antioxidant activities against Fe2+-cysteine-induced rat liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated.

A Tri-O-Bridged Diels-Alder Adduct from Cortex Mori Radicis.

Sanggenon X, an unusual tri-O-bridged Diels-Alder adduct, was isolated from Cortex Mori Radicis. Its structure was established by spectroscopic analysis, including NMR and HR-MS (High Resolution Mass Spectrometry). Sanggenon X contained three O-bridged rings, where the oxygenated bridgeheads were all quaternary carbons. Chemical methylation was carried out to deduce the linkages of the three O-bridges. The absolute configuration was determined by calculating the ECD (Electronic Circular Dichroism) using the TDDFT (Time-Dependent Density Functional Theory) method. Sanggenon X showed significant antioxidant activity against Fe2+-Cys-induced lipid peroxidation in rat liver microsomes, and was as effective as the positive control, curcumin.

Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids and Their Homologues.

Isoquercitrin, (IQ, quercetin-3-O-β-d-glucopyranoside) is known for strong chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic acids containing an aromatic ring brings entirely new properties to these compounds. Here, we describe the chemical and enzymatic synthesis of a series of IQ derivatives at the C-6″. IQ benzoate, phenylacetate, phenylpropanoate and cinnamate were prepared from respective vinyl esters using Novozym 435 (Lipase B from Candida antarctica immobilized on acrylic resin). The enzymatic procedure gave no products with “hydroxyaromatic” acids, their vinyl esters nor with their benzyl-protected forms. A chemical protection/deprotection method using Steglich reaction yielded IQ 4-hydroxybenzoate, vanillate and gallate. In case of p-coumaric, caffeic, and ferulic acid, the deprotection lead to the saturation of the double bonds at the phenylpropanoic moiety and yielded 4-hydroxy-, 3,4-dihydroxy- and 3-methoxy-4-hydroxy-phenylpropanoates. Reducing capacity of the cinnamate, gallate and 4-hydroxyphenylpropanoate towards Folin-Ciocalteau reagent was significantly lower than that of IQ, while other derivatives displayed slightly better or comparable capacity. Compared to isoquercitrin, most derivatives were less active in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, but they showed significantly better 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid, ABTS) scavenging activity and were substantially more active in the inhibition of tert-butylhydroperoxide induced lipid peroxidation of rat liver microsomes. The most active compounds were the hydroxyphenylpropanoates.

A new styrene dimer derivative from Litsea greenmaniana

A new styrene dimer derivative has been isolated from the branch of Litsea greenmaniana by column chromatography over silica gel and Sephadex LH-20, as well as semi-preparative HPLC. Its structure was identified by spectroscopic data analysis (MS, UV, IR, 1D and 2D NMR) as (E)-2,4-bis(p-hydroxyphenyl)-2-butenol, named as listeanol. At a concentration of 1×10-5 mol•L⁻¹, compound 1 was inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), antioxidant activity in Fe²⁺-cystine-induced rat liver microsomal lipid peroxidation, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).

In vitro evaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

ABSTRACTCurcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer). Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic® P 123 or Pluronic® F 127 triblock copolymers and evaluate the antioxidant and neuroprotective effects after micellization. The micelles were prepared and loaded with curcumin by applying the dissolution method. Higher encapsulation efficiency was observed in the micelles formulated with Pluronic® P 123. These micelles were characterized with small size and narrow size distribution. The effects of micellar curcumin were investigated in two in vitro models. First, the capacity of micellar curcumin to inhibit iron/ascorbic acid-induced lipid peroxidation in rat liver microsomes was evaluated. Micellar curcumin and free drug showed similar inhibition of lipid peroxidation. Second, micellar curcumin and free curcumin showed protective potential in a model of 6-hydroxydopamine induced neurotoxicity in rat brain synaptosomes. The results from both methods indicated preservation of antioxidant and neuroprotective activity of curcumin in micelles. The small micellar size, high loading capacity and preservation of antioxidant activity of curcumin into Pluronic micelles, suggested their further evaluation as a curcumin delivery system.

Phenolic constituents from the roots of Alangium chinense

Three new phenolics (1–3) and twenty-eight known compounds (4–31) were isolated from an ethanolic extract of roots of Alangium chinense. Compound 11 exhibited antiviral activity against Coxsackie virus B3 with IC50 values of 16.89μmol/L. Compounds 1, 10–17, 19–21, and 23 showed strong antioxidant activity against Fe2+-cysteine-induced rat liver microsomal lipid peroxidation, with IC50 values of 0.14–8.18μmol/L.

4-Hydroxybenzyl-substituted glutathione derivatives from Gastrodia elata

Seven new 4-hydroxybenzyl-substituted glutathione derivatives (2–8), together with a known analogue (1), were isolated from the aqueous extract of Gastrodia elata Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of 1–8 were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in 3–6 with those of S-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (9–12) synthesized as authentic samples. The configurations of 9–12 were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of 1, 3, 5, 7, and 8 were verified by synthesis. Compound 3 was active against serum deprivation-induced PC12 cell damage and synthetic 9–14 exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation.