Lipid Peroxidation In Liver Microsomes Research Articles

Hematopoietic Recovery and Amelioration of Radiation-Induced Lethality by the Vitamin E Isoform δ-Tocotrienol

δ-Tocotrienol (DT3), a vitamin E isoform, is associated with strong antioxidant and immunomodulatory properties. We confirmed the potent antioxidant activity in membrane systems and showed that DT3 is an effective radiation protector and mitigator. DT3 (4 μM, P < 0.001) inhibited lipid peroxidation in mouse liver microsomes and nitric oxide (NO) formation (20 μM DT3, P < 0.01) in RAW264.7 cells, a murine alveolar macrophage line. In CD2F1 mice exposed to lethal total-body radiation from a (60)Co γ-radiation source, a single subcutaneous (s.c.) injection of DT3 before or after irradiation produced a significant increase in 30-day survival. DT3 was effective from 18.75 to 300 mg/kg (--24 h, P < 0.001). A single dose of 150 or 300 mg/kg DT3 given 24 h before irradiation (radioprotection) resulted in dose reduction factors (DRFs) of 1.19 and 1.27, respectively (P < 0.001). Further, DT3 reduced radiation lethality when administered 2, 6 or 12 h after irradiation, and 150 mg/kg DT3 administered 2 h after exposure conferred a DRF of 1.1 (mitigation). The optimum schedule of 300 mg/kg DT3 24 h prior to 7 Gy significantly reduced pancytopenia compared to irradiated controls (P < 0.05). The large therapeutic potential of and multi-lineage hematopoietic recovery for DT3 warrants further studies.

Constituents of Gymnadenia conopsea

To investigate the chemical constituents of tuber of Gymnadenia conopsea. The constituents were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. Thirty-four compounds were isolated. Their structures were identified as six 2-isobutyltartrate benzyl ester glucosides: coelovirin A (1), coelovirin B (2), coelovirin E (3), coelovirin D (4), dactylorhin B (5) and loroglossin (6). Three 2-isobutylmalate benzyl ester glucosides: dactylorhin A (7), dactylorhin E (8) and militarine (9). Three lignans: arctigenin (10), lappaol A (11) and lappaol F (12). Six aromatic acid (alhyde or alcohol) derivatives: 4-beta-D-glucopyranosyloxyl-trans-phenylpropenoic acid (13), 4-beta-D-glucopyranosyloxyl-cis-phenylpropenoic acid (14), gastrodin (15), 4-beta-D-glucopyranosyloxylphenylaldehyde (16), 4-beta-D-glucopyranosyloxylbenzyl methyl ether (17), 4-beta-D-glucopyranosyloxyloxylbenzyl ethyl ether (18), and bis(4-hydroxybenzyl) ether mono 4-O-beta-D-glucopyranoside (19). Four cyclodipeptides: cyclo(L-Leu-L-Tyr) (20), cyclo(L-Leu-L-Pro) (21), cyclo(L-Val-L-Tyr) (22), and cyclo(L-Ala-D-Phe) (23). One N6-substituted andenosine: N6-(4-hydroxybenzyl)-adenine riboside (24). An aromatic amide: N-trans-feruloyltyramine (25). Nine aromatic acids (or aldehyde or alcohol): 3-hydroxybenzoic acid (26), 4-hydroxyisophthalic acid (27), 4-hydroxybenzyl alcohol (28), 4-hydroxybenzyl methyl ether (29), 4-hydroxybenzylaldehyde (30), 4-hydroxybenzoic acic (31), 4-hydroxy-3-methoxybenzoic acid (32), trans-p-hydroxyphenylpropenoic acid (33), and cis-p-hydroxyphenylpropenoic acid (34). At a concentration of 1.0 x 10(-6) mol x L(-1), compounds 10-12 showed antioxidative activity inhibiting Fe(+2) -cystine induced rat liver microsomal lipid peroxidation with inhibitory rates of 53%, 59%, and 52%, respectively(positive control VE with 35% inhibition). These compounds were obtained from the genus Gymnadenia for the first time except for 5-7, 9, 15, 28-34. Compounds 10-12 possess antioxidant activity.

Flavonoids from Cleistocalyx operculatus Buds and their Cytotoxic Activity

Cleistocalyx operculatus (Roxb.) Merr and Perry (Myrtaceae) is a well-known medicinal plant, widely distributed and propagated in China, Vietnam and some other tropical countries. Several species of Cleistocalyx are used in folk medicine. In Vietnam, C. operculatus is commonly called “Voi”. The flower buds (“Nu Voi”) and leaves (“La Voi”) have been used to make a beverage since ancient times. 1 The buds are commonly used as an ingredient for tonic drinks in Southern China. 2 The water extract of C. operculatus buds was shown to increase the contractility and decrease the frequency of contraction in an isolated rat heart perfusion system. 3 It showed strong protective effects on lipid peroxidation in rat liver microsomes and on the H2O2induced trauma of PC12 cells. 4 C. operculatus extract showed inhibitory activity against the α-glucosidase, rat-intestinal maltase, sucrase activities, and is considered a promising material for preventing and treating diabetes. 5 Recently, the essential oil of the C. operculatus buds was investigated for its in vitro and in vivo anti-inflammatory activities. These results suggested that its essential oil might exert an anti-inflammatory effect by suppressing the expression of pro-inflammatory cytokines, which is mediated, at least in part, by blocking the NF-κB activation. 6

Cytochrome-P450 2B1 gene silencing attenuates puromycin aminonucleoside-induced cytotoxicity in glomerular epithelial cells

Previously, we demonstrated that cytochrome P450 2B1 (CYP2B1) can generate reactive oxygen species in puromycin aminonucleoside (PAN)-induced nephrotic syndrome, an animal model of minimal-change disease in humans. In this study we found that overexpression of CYP2B1 in rat glomerular epithelial cells in vitro significantly increased PAN-induced reactive oxygen species generation, cytotoxicity, cell death, and collapse of the actin cytoskeleton. All of these pathological changes were markedly attenuated by siRNA-induced CYP2B1 silencing. The cellular CYP2B1 protein content was significantly decreased whereas its mRNA level was markedly increased, suggesting regulation by protein degradation rather than transcriptional inhibition in the PAN-treated glomerular epithelial cells. This degradation of CYP2B1 was accompanied by the induction of heme oxygenase-1, an important indicator of heme-induced oxidative stress. In PAN-treated CYP2B1-silenced glomerular epithelial cells the induction of heme oxygenase-1 and caspase-3 activity were significantly decreased. Further, cleavage of the stress-induced pro-apoptotic endoplasmic reticulum-specific pro-caspase-12 was prevented in the silenced cells. Our results support a pivotal role of CYP2B1 for reactive oxygen species production in the endoplasmic reticulum in PAN-induced cytotoxicity.

ChemInform Abstract: Synthesis and Antioxidant Properties of Some New Flavone Derivatives on Lipid Peroxidation in the Rat Liver.

A series of 2'-, 3'-, 4'- and 6-substituted flavone derivatives was synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. Retinoic acid, at 10(-4) M concentration, decreased the LP level by about 34%. A significant decrease in male liver microsomal LP level was noted for the compounds 3d, 1a, 3b and 4b at a concentration of 10(-4) M (100%, 95%, 75% and 62%, respectively).

Chemical constituents of stems and branches of Adina polycephala

To investigate chemical constituents of the stems and branches of Adina polycephala and their pharmacological activities. The constituents were isolated by a combination of various chromatographic techniques including column chromatography on silica gel, Sephadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, anti-inflammatory, anti-oxidant, anti-HIV, neuroprotective and anti-diabetic activities were screened by using cell-based models. Twenty-eight constituents were isolated. Their structures were identified as clemochinenoside B (1), kelampayoside A (2), osmanthuside H (3), 4-hydroxy-3-methoxyphenol-beta-D-[6-O-(4-hydroxy-3,5-dimethoxylbenzoate)]-glucopyranoside (4), and syringic acid beta-D-glucopyranosyl ester (5). Ten iridoidal glycosides: geniposidic acid (6), geniposide (7), 6beta-hydroxygeniposide (8), 6beta-hydroxygeniposide (9), ixoside (10), ixoside 11-methyl ester (11), 11-methyl forsythide (12), 7beta-hydroxysplendoside (13), gardoside (14) and mussaenosidic acid (15), (+) -pinoresinol (16), (+) -medioresinol (17), (+) -syringaresinol (18), (-)-lariciresinol (19), evofolin-B (20), alpha-hydroxyacetovaillone (21), syringic acid (22), vanillin (23), 3, 4, 5-trimethoxyphenol (24), and 2,6-dimethoxy-1, 4-benzoquinone (25), beta-sitosterol (26), mannitol (27), and daucosterol (28). At a concentration of 1.0 x 10(-5) mol x L(-1), these compounds were inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), anti-inflammatory activity against the release of beta-glucuronidase in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF), antioxidant activity in Fe(2+)-cystine-induced rat liver microsomal lipid peroxidation, anti-HIV activity against HIV-1 replication, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Compounds 1-20 were obtained from the genus Adina for the first time. The 13C-NMR data of compounds 10 and 11 were reassigned. A further evaluation of pharmacological activity of these compounds is expected.

Bauhenia tomentosa Stimulates the Immune System and Scavenges Free-Radical Generation in vitro and in vivo

A methanolic extract of Bauhinia tomentosa was studied for its immunomodulatory, antioxidant, and anti-inflammatory activity in BALB/c mice. Intraperitoneal administration of the extract significantly increased the total leukocyte account (10075 +/- 542 cells/cm2) on the 18th day, bone marrow cellularity (93.1 x 10(5) +/- 3.35 cells/femur), and alpha-esterase positive cells (1332 +/- 32 cells/4000 bone marrow cells) when compared with untreated control mice. The weights of lymphoid organs, such as spleen and thymus, also increased. An evaluation of the antioxidant activity of B. tomentosa revealed that the extract inhibited non-enzymic lipid peroxidation in mouse liver microsomes at all concentrations, with an IC50 value of 90 microg/ml. For nitric oxide radical scavenging activity, the IC50 of B. tomentosa was 65.0 microg/ml, indicating that B. tomentosa is a good antioxidant. The anti-inflammatory effect B. tomentosa also significantly reduced acute inflammation of the paw edema induced by carrageenan and formalin.

Design, synthesis and biological evaluation of novel beta-substituted indol-3-yl ethylamido melatoninergic analogues.

A series of new melatonin analogues have been synthesized. Interestingly, two of the new compounds, 11c and 11e, which did not show any appreciable affinity for the melatonin receptor, were found to be potent inhibitors of lipid peroxidation in rat liver microsomes. Analogue 11c, in particular, is a better antioxidant than melatonin.

Antioxidant properties of novel lipophilic ascorbic acid analogues.

Structural modifications of ascorbic acid by the introduction of lipophilic moieties has led to derivatives with increased stability against thermal and oxidative degradation. Two series of new lipophilic ascorbic analogues were synthesized to obtain antioxidants devoid of autooxidant properties: 4-benzoyl-3-hydroxyfuran-2(5H)-ones (3a-j) and 4-acetyl-5-aryl-3,4-dihydrofuran-2(5H)ones (5a-f). These compounds were submitted to three different tests: reduction of the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH); superoxide-anion scavenging assay; and lipid-peroxidation assay. Most compounds interacted with DPPH: at a concentration of 5 x 10(-3) M, the reducing activity of 4-benzoyl derivatives, 3c and 3h, was more than 50%; under the same conditions, the rate of inhibition for 4-acetylbutanolides, 5a and 5f, reached 60.6% and 87.3%, respectively; 93.3% inhibition was observed with ascorbic acid. In the superoxide-anion scavenging assay, at a concentration of 1 mg mL(-1), 4-benzoyl derivatives, 3g and 3i, exhibited a good activity, with IC50 (dose resulting in 50% inhibition) values of 1.45 and 1.35 x 10(-3) M, respectively. 4-Acetylbutanolide, 5f, significantly inhibited the Fe2+/ADP/ascorbate-induced lipid peroxidation of rat liver microsomes with an IC50 of 4.9 x 10(-4) M. This study demonstrates that enol functions in the structure of ascorbic acid analogues are not absolutely essential to bring about antioxidant effects.

Effect of purified saponin mixture from Astragalus corniculatus on enzyme- and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive rats

The aim of the following study was to evaluate the effect of a purified saponin mixture (PSM), isolated from Astragalus corniculatus Bieb. (Fabaceae), on enzyme-induced and non-enzyme-induced lipid peroxidation (LPO), in liver microsomes from spontaneously hypertensive rats (SHRs) - strain Okamoto Aoki, as compared to normotensive Wistar rats (NTRs). The enzyme-induced lipid peroxidation was performed by incubating rat liver microsomes with carbonetetrachloride (CCl(4)) in the presence of NADPH. In nonenzyme-induced LPO, the microsomes were incubated with a solution of iron sulphate and ascorbinic acid (Fe(2+)/AA). The effect of PSM (196.5 microg/ml) was assessed at 20 minutes' incubation time. MDA, a product of LPO, was measured spectrophotometrically. The results of our study showed that the initial MDA quantity in SHRs was significantly higher, than in NTRs. The incubation of the microsomes from both strains with PSM (196.5 microg/ml), resulted in significant reduction of MDA level, by 25% in SHRs. In NTRs, the formation of MDA was unchanged. In enzyme-induced LPO model, PSM significantly decreased the formation of MDA, by 55% in NTRs and by 35% in SHRs, compared to the respective control groups. In the model of non-enzyme induced LPO, PSM significantly decreased the formation of MDA by 95% in NTRs and practically restored it to the control level. The MDA quantity in SHR's microsomes was reduced by 25%. According to the results of this experiment we could conclude that PSM, isolated from Astragalus corniculatus, shows antioxidant activity both in SHRs and NTRs and the effect in NTRs is more pronounced.

Antioxidant and antiglycation properties of triterpenoid saponins from Aralia taibaiensis traditionally used for treating diabetes mellitus

Our previous study has demonstrated that the antidiabetic activity of the extract of root bark of Aralia taibaiensis (EAT) was correlated with its combined antioxidant and antiglycation properties. To confirm further the constituents responsible, 12 triterpenoid saponins were isolated from EAT and examined for their antioxidant and antiglycation activities. The antioxidant activities of the pure compounds and EAT were evaluated by studying the inhibition of lipid peroxidation in rat liver microsomes induced by ascorbate/Fe2+, cumine hydroperoxide (CHP) or CCl4/reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH). The antioxidant capacities were also evaluated by studying the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The antiglycation activities of the pure compounds and EAT were evaluated by hemoglobin–δ-gluconolactone (δ-Glu) assay, bovine serum albumin (BSA)-glucose assay and N-acetyl-glycyllysine methyl ester (GK peptide)-ribose assay. EAT outperformed other compounds in all the assays. The compounds with best antioxidant (TA7, TA24 and TA35) and antiglycation (TA21, TA9 and TA24) activities in different assays were screened out. The results suggest that the antioxidant and antiglycation properties of EAT could be explained, at least in part, by the synergistic effect of pure compounds isolated from it.

The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.

Effect of Polyphenolic Compounds from Solanum torvum on Plasma Lipid Peroxidation, Superoxide anion and Cytochrome P450 2E1 in Human Liver Microsomes

Previous studies presented evidence that plants contain antioxidants that have free radical-scavenging properties. Overproduction of free radicals leads to oxidative stress, a factor associated with a variety of diseases, such as diabetes. Cytochrome P450 2E1 enzymes (CYP2E1) are involved in drug metabolism in the liver and metabolism of DNA-reaction generating intra-mitochondrial ROS, which leads to micro- and macro-vascular pathology in diabetes. Plant-based chemicals can affect CYP2E1 enzymes and related defense mechanisms, possibly leading to protection against oxidative stress. We investigated the effect of Solanum torvum (ST) extracts on the inhibition of CYP2E1 activity in human liver microsomes. ST extract was analyzed for antioxidant activity by the ABTS method. Polyphenolic compounds were measured by the total phenol content using the Folin-Ciocalteau reagent. Flavonoid and tannin content were analyzed by standard methods. Oxidative stress was evaluated by measuring lipid peroxidation by TBARS and superoxide anion scavenging levels in plasma from diabetic patients. Results showed that 10 mg/ml of ST had CYP2E1 catalytic inhibiting activity (57.16 %). The IC50 value of CYP2E1 catalytic inhibiting activity level was 5.14 mg/ml by concentration in a dependent manner. One gram of concentrated ST extract had an antioxidant activity index of 3.68 mg of trolox and 360.53 mg of ascorbic acid equivalent. Effects on free radical-scavenging, as measured by TBARS and superoxide anion, showed IC50 values of 20.60 and 10.26 microg/ml, respectively. Polyphenolic compounds found included phenol, flavonoid and tannin, measuring 160.30, 104.36 and 65.91 mg/g, respectively. These results imply that ST is a natural source of polyphenolic antioxidants, which have cytochrome P450 2E1 enzyme inhibiting and free radical scavenging properties, as related to lipid peroxidation and superoxide anion activity. ST could potentially be used for reducing oxidative stress in diabetes. Study for usage as a conventional medicine, including dosage and chronic toxicity in humans, should be pursued.

Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation

In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, α-iodinated naphthofuranquinone (NPPN-3223), β-iodinated naphthofuranquinone (NPPN-3222) and β-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate–lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH–P450 reductase system, as detected by ESR measurements. These results support the hypothesis that naphthofuranquinones reduction by microsomal NADPH–P450 reductase and semiquinone oxidation by molecular oxygen diverts electrons, preventing microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones formed by naphthofuranquinones reduction would be capable of lipid peroxidation inhibition and on interacting with the lipid peroxide radicals can lead to an antioxidant effect as we suggested for NPPN-3226 in close agreement to the inhibition of ascorbate–lipid peroxidation. Due to the properties of these molecules and their incoming structure developments, naphthofuranquinones would be considered as potentially promising therapeutic agents, mainly against Chagas disease.

Antioxidant activity of methanolic extract of Bombax ceiba

The antioxidant activity of a methanolic extract of Bombax ceiba was evaluated using several antioxidant assays, in terms of its: (i) ability to scavenge DPPH (1,1-diphenyl-2-picryl-hydrazyl) and hydroxyl free radicals; (ii) action against lipid peroxidation (in rat liver microsomes and soy bean phosphatidylcholine liposomes), induced by ascorbyl radicals and peroxynitrite; and (iii) effect on myeloperoxidase activity. The cytotoxicity was monitored through the mitochondrial activity in the Vero cell line. The extract showed antioxidant activity in all assays, the EC50 (μg/ml) for DPPH was 87 and for lipid peroxidation of microsomes and soy bean liposomes induced by ascorbyl radicals were 141 and 105, respectively, and by peroxynitrite were 115 and 77, respectively. The K0.5 value for myeloperoxidase activity inhibition by the extract was 264 μg/ml. The extract showed very low toxicity toward Vero cells.

Antioxidant, antiinflammatory and antiinvasive activities of biopolyphenolics

A large number of polyphenolic and heterocyclic compounds, i.e. 4-methylcoumarins, 4methylthionocoumarins, xanthones, pyrazoles, pyrazolylacrylonitriles, flavones and isoflavones have been tested for their antioxidant activity towards NADPH-catalysed liver-microsomal lipid peroxidation with a view to establish their structure-activity relationship. Inhibition of microsomal lipid peroxidation by 7,8-dihydroxy-4-methylcoumarin (DHMC, 2) and 7,8diacetoxy-4-methylcoumarin (DAMC, 3) was intriguing. We also found that dihydroxy and diacetoxy derivatives of 4-methylthionocoumarin were more potent in comparison to the corresponding coumarin derivatives in inhibiting TNF-α induced expression of ICAM-1. The effect of nine different xanthones has been examined on the modulation of cytokine-induced expression of ICAM-1 in human endothelial cells. 1,4-Dihydroxyxanthone (10) showed enhanced antioxidant activity as well as the inhibition of the expression of cell adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin on endothelial cells in a concentration and time dependent manner. Antioxidant activity of different pyrazoles and pyrazolylacrylonitriles and antiinvasive activity of flavones and isoflavones against solid tumors have also been studied.

Anti-dyslipidemic and antioxidant activities of different fractions of Pongamia pinnata (lin.) fruits

Ethanol extract of Pongamia pinnata fruits was evaluated. In an acute experiment, hyperlipidemia in rats was induced by administration of triton WR-1339 (400 mg/kg, i.p.). P. pinnata fractions and guggulipid were fed orally at a dose of 250 mg/kg simultaneously with triton. Only chloroform-soluble fractions (B) exerted a significant lowering effect on levels of plasma levels of total cholesterol, triglycerides, and phospholipid in triton-induced hyperlipidemic rats. The antioxidant activity of all four fractions A, B, C and D was assessed in vitro. The chloroform (B) and butanol (C) extracts of P. pinnata at concentrations of 500 μg significantly inhibited the generation of superoxide anions and hydroxyl radical as well as the reaction of lipid peroxidation in rat liver microsomes induced by Fe+2. The most active fraction (C) was further tested for its anti-dyslipidemic activity at a dose of 500 mg/kg p.o. in a fructose-rich high-fat diet hamster model of dyslipidemia, in which the treatment caused significant reversal in the plasma level of triglyceride, total cholesterol, HDL cholesterol glucose, and glycerol. No significant decrease in animal body weight and quantity of food intake was observed.

Diarylheptanoids and a monoterpenoid from the rhizomes of Zingiber officinale: antioxidant and cytoprotective properties.

Three new diarylheptanoids and one new monoterpenoid were isolated from the rhizomes of Zingiber officinale together with four known diarylheptanoids, 5-8. Their structures were elucidated mainly by spectroscopic methods, and they were deduced as 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2 H-pyran-2-yl]-3-methoxybenzene-1,2-diol (1), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 S-sulfonate (2), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 R-sulfonate (3), and hydroxycineole-10-O-beta-D-glucopyranoside (4), respectively. Among the isolated compounds, compounds 1, 5, and 8 exhibited strong superoxide anion radical scavenging activities in a phenazine methosulfate-NADH system. In a more biological system, these compounds were demonstrated to exhibit potent protection against lipid peroxidation in mouse liver microsomes exposed to oxidative conditions. These compounds were subsequently tested on primary cultures of rat hepatocytes exposed to oxidative damage, and definitive cytoprotective actions were found.

Synthesis and evaluation of N-substituted indole-3-carboxamide derivatives as inhibitors of lipid peroxidation and superoxide anion formation

The in vitro antioxidant effects of novel N-substituted indole-3-carboxamides (I3CDs) 1-10 on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels and their free radicals scavenging properties were determined by the inhibition of superoxide anion formation (SOD). Among the synthesized compounds, 4, 5, 8 and 9 significantly inhibited SOD with an inhibition range at 84–100% at 10− 3 M concentration. The presence of halo substituents both ortho- and para- positions of these compounds resulted 100% inhibition of SOD. Comparison the activity results of halogenated and non-halogenated derivatives suggested that the halogenated compounds are more active than the non-halogenated compounds. On the other hand, the introduction of a para fluoro benzyl in the 1-position of indole (compounds 7, 8) has more impact on the SOD inhibition when the benzamide ring was mono halogenated. However, none of other compounds had a significant inhibitory effects on the level of lipid peroxidation.

Antioxidant and antiglycation properties of total saponins extracted from traditional Chinese medicine used to treat diabetes mellitus

Eleven antidiabetic traditional Chinese medicine (TCM) extracts rich in saponins were examined for their antioxidant and antiglycation activities. The antioxidant activities of these extracts were evaluated by studying the inhibition of lipid peroxidation in rat liver microsomes induced by ascorbate/Fe2+, cumine hydroperoxide (CHP) or CCl4/reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH). The antioxidant capacities were also evaluated by studying the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical. The antiglycation activities of these extracts were evaluated by hemoglobin-delta-gluconolactone (delta-Glu) assay, bovine serum albumin (BSA)-glucose assay and N-acetyl-glycyl-lysine methyl ester (GK peptide)-ribose assay. Aralia taibaiensis outperformed other extracts in most of the assays except inhibition of early glycation products formation, where Acanthopanax senticosus showed higher activity. Aralia taibaiensis was particularly potent in inhibiting the late glycation and formation of advanced glycation end products (AGEs) on proteins. The antioxidant and antiglycation activities of most extracts were correlated with the saponin content. The results demonstrate that the antidiabetic activities of most extracts could be explained, at least in part, by their combined antioxidant and antiglycation properties.