Potent Antioxidant Potential Research Articles

Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis.

Attenuation of mitochondrial oxidative stress by morin during chemical carcinogen-mediated mammary carcinogenesis

In this study we evaluated the effects of morin on the mitochondrial functions with reference to mitochondrial citric acid cycle enzymes, respiratory chain complex enzymes, membrane bound ATPases and protein-bound carbohydrates in mammary tissues of 7,12-dimethyl benz(a)-anthracene (DMBA)-induced mammary carcinoma of Sprague-Dawley rats. Adult female Sprague-Dawley rats were induced mammary carcinoma by administration of DMBA (25mg/kg b.wt.) orally. The normal and cancer-induced rats were treated with morin (50mg/kg b.wt.) for three times per week for 13 weeks. Cancer-induced rats showed a significantly increased level of lipid peroxidation (LPO) products and protein-bound carbohydrates with concomitant decreased levels of nonenzymic antioxidants (vitamin C, reduced glutathione [GSH]) and vitamin E and enzymic antioxidants (superoxide dismutase [SOD]), catalase (CAT) and glutathione peroxidase (GPx) in the mammary tissue. Decreased levels of ATPases, citric acid cycle enzymes and respiratory chain enzymes were observed in the mammary tissue of tumor bearing group of rats. Treatment with morin brought back lipid peroxidation products, nonenzymic and enzymic antioxidants to near normalcy. Since morin treatment decreases lipid peroxidation and enhances antioxidants and enzymes involved in the biochemical pathways, it may play a critical role in oxidative stress-related changes in cancer-induced rats and may possess a potent antioxidant potential to protect subcellular organelles being damaged by oxidative stress.

ANTIHYPERGLYCEMIC AND ANTIOXIDANT POTENTIAL OF POLYSACCHARIDE FRACTION FROM PORTULACA OLERACEA SEEDS AGAINST STREPTOZOTOCIN-INDUCED DIABETES IN RATS

ABSTRACT The present study envisaged the antidiabetic and antioxidant potential role of polysaccharide fraction of Portulaca oleracea (P. oleracea polysaccharide fraction [PPFt]) against streptozotocin (STZ)-induced (50 mg/kg, intraperitoneal) diabetes in experimental animals. After 3 weeks of oral treatment with PPFt (25 and 50 mg/kg), significant dose-dependent reduction in blood glucose, Thiobarbituric Acid Reactive Substances and subsequent increase in total reduced glutathione levels and glutathione peroxidase activity was observed in the diabetic animals. Enzymatic antioxidant defense, catalase and superoxide dismutase were significantly reduced after STZ administration and concomitant administration of PPFt significantly reversed the levels of these enzymes near to normal values. These findings strongly indicate that PPFt could protect against the STZ-induced hyperglycemia and disturbance in lysosomal enzymes in a dose-dependent manner. PRACTICAL APPLICATIONS Portulaca oleracea seeds exhibit good nutritional value with potent antidiabetic and antioxidant potential, which supports it to be used as excellent food supplement for diabetics. The present investigation was therefore undertaken to evaluate the possible role of polysaccharides fraction of P. oleracea against streptozotocin-induced oxidative stress in experimental diabetic rats. Our result indicates that polysaccharide fraction of P. oleracea possesses moderate antidiabetic activity and exhibited potent antioxidant potential in diabetic conditions. These findings strongly indicate that polysaccharides could protect against oxidative stress in diabetic rats.

Chemopreventive and antioxidant efficacy of (6)-paradol in 7, 12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis

The present study evaluated the chemopreventive potential of (6)-paradol, a pungent phenolic constituent of ginger, on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. The mechanistic pathway for the chemopreventive potential of (6)-paradol was evaluated by measuring the status of tumor incidence, volume and burden as well as by analyzing the status of phase II detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinoma was induced in hamster buccal pouches by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% tumor formation with marked biochemical abnormalities in tumor-bearing animals compared to control animals. Oral administration of 30mg/kg b.w. (6)-paradol to DMBA-treated hamsters on alternate days from DMBA painting for 14 weeks, significantly reduced the formation of tumors and improved the status of detoxification agents, lipid peroxidation and antioxidants. Therefore, the present study suggests that (6)-paradol has potent chemopreventive, anti-lipid peroxidative and antioxidant potentials as well as a modulating effect on phase II detoxification enzyme and reduced glutathione (GSH) in DMBA-induced hamster buccal pouch carcinogenesis.

A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity

We have previously reported the successful replacement of a carboxylic acid functionality with that of a difluorophenolic group on the known aldose reductase inhibitors (ARIs) of 2-(phenylsulfonamido)acetic acid chemotype. In the present work, based on bioisosteric principles, additional 2,6-difluorophenol and tetrazole, methylsulfonylamide, and isoxazolidin-3-one phenylsulfonamide derivatives were synthesized and tested in vitro in protocols primarily related to the long-term diabetic complications. Most of the compounds were found as ARIs at IC(50) < 100 μM, while the introduction of the 4-bromo-2-fluorobenzyl group in a phenylsulfonamidodifluorophenol structure resulted in a compound (4c) presenting a submicromolar inhibitory profile. However, the derivatives of tetrazole, methylsulfonylamine, and the (R)-enantiomer of isoxazolidin-3-one did not exhibit appreciable ARI activity. The selectivity of the active ARIs is also discussed. Furthermore, the synthesized compounds exhibited potent antioxidant potential (homogeneous and heterogeneous systems).

In vitro N1-Amylase Inhibition and Antihyperglycemic Activity of Helicteres isora in Streptozotocin-Induced Rats

In present study, in vitro N1-amylase inhibition and streptozotocin-induced oxidative stress were used to evaluate hypoglycemic effects of Helicteres isora (sterculiaceae). Antidiabetic treatment with of H. isora extract (100 mg/kg and 250 mg/kg body weight) for three weeks showed significant reduction in thiobarbituriuc acid reactive substances (TBRAS) and glutathione reductase (GSH-R) in both liver and kidney. The treatment with H. isora significantly altered the glutathione (GSH) and GSH-R to be comparable with the control group. H. isora and tolbutamide treated rats showed decreased lipid peroxidation that is associated with increased activity of superoxide dismutase (SOD) and catalase (CAT).The result of this study thus shows that at 1000 N less than g /ml there was maximum inhibition by the H. isora extract (53.75 %). It also possesses moderate antidiabetic activity, but it exhibits potent antioxidant potential in diabetic conditions.

Action of Portulaca oleracea against Streptozotocin-Induced Oxidative Stress in Experimental Diabetic Rats

Antidiabetic treatment with an extract of Portulaca oleracea leaves (100mg/kg and 250mg/kg body weight) for three weeks showed a significant reduction in thiobarbituric acid reactive substances (TBRAS) and an increase in glutathione reductase (GSH-R) in both the liver and kidney of STZ diabetic rats. The treatment with P. oleracea significantly altered the glutathione and GSH-R to be comparable with the control group. P. oleracea- and tolbutamide-treated rats showed decreased lipid peroxidation that is associated with increased activity of superoxide dismutase (SOD) and catalase(CAT). The effects of P. oleracea on tissue lipid peroxidation and antioxidant status in diabetic animals have not been studied before. The result of this study thus shows that although P. oleracea extract possesses moderate antidiabetic activity, it exhibits potent antioxidant potential in diabetic conditions.

Phenolic Constituents from the Stem Bark of Magnolia officinalis

Three new compounds, magnolianone (1), erythro-honokitriol (2), and threo-honokitriol (3), together with 14 known compounds, magnaldehyde (4), magnatriol B (5), randaiol (6), obovatol (7), magnolignan B (8a and 8b), magnolol, honokiol (9), p-hydroxylbenzaldehyde, coniferaldehyde, coniferol alcohol, syringaldehyde, syringaresinol, and acteoside, were isolated from the MeOH-soluble part of a water extract of the stem bark of Magnolia officinalis. Among these compounds, 2-8b were studied for anti-inflammatory and antioxidative activities. Compound 7 displayed more potent antioxidative potential than 9. Compounds 4-7 effectively inhibited LPS-induced NO production, whereas 5 and 6 were more potent than 9.

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.

Hydroxy-1-aryl-isochromans: protective compounds against lipid peroxidation and cellular nitrosative stress

Hydroxy-1-aryl-isochromans are a novel class of polyphenolic heterocyclic compounds with potent antioxidative potential. Here we investigated the protective effects of hydroxy-1-aryl-isochroman derivatives against lipid peroxidation and nitrosative stress as a function of their degree of hydroxylation. Measurements of thiobarbituric acid reactive substances (TBARS) in rat brain mitochondria, nitric oxide analysis in microglia cultures, and cell viability analysis were performed. We found that hydroxyl-1-aryl-isochroman derivatives with two, three, and four hydroxyl groups (ISO-2, ISO-3, and ISO-4, respectively) display a higher activity against mitochondrial lipid peroxidation than the corresponding derivative without hydroxyl groups (ISO-0) as well as the reference antioxidant Trolox. However, ISO-0 strongly reduced microglial nitric oxide production, whereas ISO-2 and ISO-4 had a less pronounced effect and ISO-3 was even ineffective. ISO-0 and ISO-3 increased the cell viability of activated microglia, whereas a minor effect of ISO-2 and no significant increase after treatment with ISO-4 could be observed. In conclusion, hydroxy-1-aryl-isochromans exhibit cytoprotective properties, besides their action against reactive oxygen/nitrogen species.

The potential of Manitoba chokecherry as a source of high natural antioxidants

AbstractConsumption of fruits and vegetables is shown to be beneficial for protecting health and preventing some chronic diseases such as cancer, cardiovascular disease, and stroke. The positive health effects have been mainly due to the contributions of their natural antioxidant capacity. Chokecherry (Prunus virginiana), a unique fruit, is a member of the Rose family and native to North America. Here we demonstrate that chokecherry fruit with strong antioxidant capacity is available in Manitoba, and that its potent antioxidant potential can be developed for health benefits in value-added applications.These findings are useful for developing novel value-added antioxidant products from chokecherry because of its phytochemical profile associated with health protection and prevention of disease. The results provide evidence essential for breeding novel cultivars of fruit plants with strong natural antioxidants.

Free Radical Scavenging Activity of a Novel Antioxidative Peptide Isolated fromIn VitroGastrointestinal Digests ofMytilus coruscus

A low-molecular-weight peptide with potent antioxidative activity was obtained from Mytilus coruscus muscle protein using an in vitro gastrointestinal digestion system. The potent antioxidant peptide, which was identified as Leu-Val-Gly-Asp-Glu-Gln-Ala-Val-Pro-Ala-Val-Cys-Val-Pro (1.59 kDa), exhibited higher protective activity against polyunsaturated fatty acid (PUFA) peroxidation than the native antioxidants, ascorbic acid and alpha-tocopherol. In a free radical scavenging assay using electron spin resonance spectroscopy, hydroxyl radical formation was quenched by 75.04% in the presence of M. coruscus peptide (50 microg/mL), which was similar to ascorbic acid. In addition, the purified peptide could also quench super-oxide and carbon-centered radicals, but those activities were weaker than for ascorbic acid. This study showed that the low-molecular-weight peptide released from in vitro gastrointestinal digestion of mussel exhibited potent antioxidant potential by inhibiting the formation of reactive oxygen species formed by the peroxidation of PUFAs.

Action of Hygrophila auriculata against streptozotocin-induced oxidative stress

Hygrophila auriculata (K. Schum.) Heine (Family: Acanthaceae) is a wild herb widely used in ‘Ayurveda’ as ‘Rasayana’ drug for treatment of various disorders. Treatment of diabetic rats with aerial parts of Hygrophila auriculata extract (HAEt, 100 and 250 mg/kg body weight) for 3 weeks showed significant reduction in blood glucose, thiobarbituric acid reactive substances (TBARS) and hydroperoxide in both liver and kidney. The treatment with HAEt significantly increased the glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT) in the drug-treated group, which is comparable to the control group. HAEt and glibenclamide-treated rats also showed decreased lipid peroxidation that is associated with increased activity of superoxide dismutase (SOD) and catalase. The ability of HAEt on tissue lipid peroxidation and antioxidant status in diabetic animals has not been studied before. The result of this study thus shows that HAEt possesses significant antidiabetic activity along with potent antioxidant potential in diabetic conditions.

Ferulic Acid Stabilizes a Solution of Vitamins C and E and Doubles its Photoprotection of Skin

Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15%l-ascorbic acid and 1%alpha-tocopherol improved chemical stability of the vitamins (C+E) and doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer.

Antioxidative effects of glycoprotein isolated from Solanum nigrum L.

Glycoprotein from Solanum nigrum L. (SNL glycoprotein) was isolated and tested for antioxidative effects on oxygen free radicals using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The free radical scavenging activities of the SNL glycoprotein are optimal in acidic pH and up to 60 degrees C. However, it has minimal activities in the presence of EDTA, although such activities are not dependent on M(2+) ions (Ca(2+), Mn(2+), and Mg(2+)) in the presence of EDTA. Interestingly, when SNL glycoprotein was treated with deactivation agents (pronase E and NaIO(4)), the DPPH radical scavenging activity was decreased compared with the SNL glycoprotein treatment alone. The antioxidative effects of SNL glycoprotein on superoxide anion and hydroxyl radical under optimal conditions revealed that SNL glycoprotein has remarkable scavenging effects on both radicals, but exhibited slightly higher scavenging effects on superoxide anion generated by the enzymatic hypoxanthine/xanthine oxidase system than on hydroxyl radicals generated by the Fenton reaction. However, SNL glycoprotein was more effective against hydroxyl radials in cell cultures (NIH/3T3). Consequently, 20 microg/mL SNL glycoprotein has a scavenging ability against superoxide anion corresponding to that of ascorbic acid. On the other hand, its hydroxyl radical scavenging activity corresponds to 0.1 microg/mL catalase. From these results, we suggest that SNL glycoprotein has potent antioxidative potential.

Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation

Increased atherosclerosis risk in hyperlipidemic patients may be a result of the enhanced oxidizability of their plasma lipoproteins. We have previously shown that hypocholesterolemic drug therapy, including the 3-hydroxy-3-methyl-glutaryl CoenzymeA (HMG-CoA) reductase inhibitors, and the hypotriglyceridemic drug bezafibrate, significantly reduced the enhanced susceptibility to oxidation of low density lipoprotein (LDL) isolated from hyperlipidemic patients. Although this antioxidative effect could not be obtained in vitro with all of these drugs, the active drug metabolites, which are formed in vivo, could affect lipoprotein oxidizability. We thus sought to analyze the effect of atorvastatin and gemfibrozil, as well as specific hydroxylated metabolites, on the susceptibility of LDL, very low density lipoprotein (VLDL), and high density lipoprotein (HDL) to oxidation. LDL oxidation induced by either copper ions (10 microM CuSO4), by the free radical generator system 2'-2'-azobis 2-amidino propane hydrochloride (5 mM AAPH), or by the J-774A.1 macrophage-like cell line, was not inhibited by the parent forms of atorvastatin or gemfibrozil, but was substantially inhibited (57-97%), in a concentration-dependent manner, by pharmacological concentrations of the o-hydroxy and the p-hydroxy metabolites of atorvastatin, as well as by the p-hydroxy metabolite (metabolite I) of gemfibrozil. On using the atorvastatin o-hydroxy metabolite and gemfibrozil metabolite I in combination an additive inhibitory effect on LDL oxidizability was found. Similar inhibitory effects (37-96%) of the above metabolites were obtained for the susceptibility of VLDL and HDL to oxidation in the oxidation systems outlined above. The inhibitory effects of these metabolites on LDL, VLDL, and HDL oxidation could be related to their free radical scavenging activity, as well as (mainly for the gemfibrozil metabolite I) to their metal ion chelation capacities. In addition, inhibition of HDL oxidation was associated with the preservation of HDL-associated paraoxonase activity. We conclude that atorvastatin hydroxy metabolites, and gemfibrozil metabolite I possess potent antioxidative potential, and as a result protect LDL, VLDL, and HDL from oxidation. We hypothesize that in addition to their beneficial lipid regulating activity, specific metabolites of both drugs may also reduce the atherogenic potential of lipoproteins through their antioxidant properties.

Antioxidant potential of ferulic acid

Ferulic acid is a ubiquitous plant constituent that arises from the metabolism of phenylalanine and tyrosine. It occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical which accounts for its potent antioxidant potential. UV absorption by ferulic acid catalyzes stable phenoxy radical formation and thereby potentiates its ability to terminate free radical chain reactions. By virtue of effectively scavenging deleterious radicals and suppressing radiation-induced oxidative reactions, ferulic acid may serve an important antioxidant function in preserving physiological integrity of cells exposed to both air and impinging UV radiation. Similar photoprotection is afforded to skin by ferulic acid dissolved in cosmetic lotions. Its addition to foods inhibits lipid peroxidation and subsequent oxidaive spoilage. By the same mechanism ferulic acid may protect against various inflammatory diseases. A number of other industrial applications are based on the antioxidant potential of ferulic acid.