Protective Effect Of Phenolic Compounds Research Articles

Neuronal cell protective effects of phenolic compounds derived from steam exploded nematode-infected pine

Pine wilt disease is one of the most serious forest diseases that kills pine trees. Most of the nematode-infected pines are fumigated or locally incinerated and are thus not appropriately utilized. This study explored methods to utilize abandoned nematode-infected pines. The chemical compositions of healthy and nematode-infected pines were analyzed, and the neuroprotective effects of phenolic compounds extracted after steam explosion treatment were investigated. In terms of chemical composition, the nematode-infected pine chips suffered more damage from the steam explosion treatment than the healthy pine chips. In addition, the total phenolic compound content showed a clear difference depending on the presence of infection and steam explosion conditions. The maximum total phenolic compound content of extracted ethanol was found when the nematode-infected pine chip was subjected to steam explosion with a severity factor (Ro) of 3.82. The steam exploded pine extract of 10 μg/mL inhibited glutamate-induced early apoptotic cell death compared to cells treated with 10 mM glutamate alone. These results suggested that steam-exploded pine can be used as an effective natural material for neuronal cell protection.

Protective Effect of Phenolic Compounds Isolated from Mugwort (Artemisia argyi) against Contrast-Induced Apoptosis in Kidney Epithelium Cell Line LLC-PK1.

We investigated whether 14 phenolic compounds isolated from Artemisia argyi could prevent the apoptotic damage caused by iodixanol, an iodinated contrast agent, on LLC-PK1 cells. Iodixanol was used to induce cytotoxicity in LLC-PK1 cells. Apoptotic cell death was observed as the fluorescence intensity emitted by annexin V and Hoechst 33342 stains. Western blotting was used to detect specific proteins. Seven phenolic compounds protected against iodixanol-induced LLC-PK1 cell death in a concentration-dependent manner. Among them, methyl caffeate exerted the strongest protective effect, and co-treatment with 50 and 100 μM methyl caffeate decreased intracellular reactive oxygen species elevated by 25 mg/mL iodixanol. In addition, the treatment of LLC-PK1 cells with iodixanol resulted in an increase in apoptotic cell death, which decreased by co-treatment with methyl caffeate. Iodixanol caused a cytotoxicity-related increase in the phosphorylation of extracellular-signal-regulated kinase, c-Jun N-terminal kinase, and P38; and a similar increase in the expression levels of kidney injury molecule-1 and cleaved caspase-3. However, the up-regulation of these proteins was reversed by co-treatment with methyl caffeate. These findings suggest that phenolic compounds isolated from A. argyi play an important role in protecting kidney epithelium cells against apoptotic damage caused by iodixanol.

Oleuropein and hydroxytyrosol protect rats’ pups against bisphenol A induced hypothyroidism

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats.

In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan Oat Cultivars.

Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition.

The Potential Protective Effects of Phenolic Compounds against Low-density Lipoprotein Oxidation.

The exact mechanism(s) of atherosclerosis in humans remains elusive, but one theory hypothesizes that this deleterious process results from the oxidative modification of low-density lipoprotein (LDL). Research suggests that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo. With regard to the different classes of flavonoids, there appears to be a structurefunction relationship between the various moieties/constituents attached to the flavonoids' three ring system and their impact at retarding LDL oxidation. This article summarizes the findings to date of both in vitro and in vivo studies using foods or phenolic extracts isolated from foodstuffs at inhibiting the incidence of LDL oxidation. Three bases: SCOPUS, Web Science, and PubMed were used for search. An often used method for the determination of antioxidant properties of natural phenolic compounds is the LDL oxidation assay. LDLs are isolated from human plasma and their oxidation is induced by Cu2+ ions or 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The sample is incubated with a phenolic extract or individual/isolated phenolic compounds. LDL oxidation is then monitored by various chemical methods (e.g., measurement of the generation of conjugated dienes and trienes). This technique confirmed the antioxidant properties of several extracts as obtained from plant material (e.g., grapes, berries, orange, grapefruit, coffee, tea, chocolate, olives, nuts) as well as the individual phenolic compounds (e.g., luteolinidin, apigenidin, caffeic acid, chlorogenic acid, catechin, quercetin, rutin). Several studies in vivo confirmed protective effects of phenolic compounds against LDL oxidation. They covered the healthy subjects with hyperlipidaemia, overweight, obesity, metabolic syndrome, heavy smokers, patients receiving haemodialysis, patients with peripheral vascular disease, and subjects at high cardiovascular risk. The studies comprise individuals of all ages, and the number of participants in the different experiments varied widely. Properly designed double-blind, placebo-controlled randomised clinical trials offer stronger evidence as to the impact of dietary phenolics consumption at retarding LDL oxidation. More such clinical trials are needed to strengthen the hypothesis that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo.

Protective effect of phenolic compounds on carbonyl-amine reactions produced by lipid-derived reactive carbonyls.

The degradation of phenylalanine initiated by 2-pentenal, 2,4-heptadienal, 4-oxo-2-pentenal, 4,5-epoxy-2-heptenal, or 4,5-epoxy-2-decenal in the presence of phenolic compounds was studied to determine the structure-activity relationship of phenolic compounds on the protection of amino compounds against modifications produced by lipid-derived carbonyls. The obtained results showed that flavan-3-ols were the most efficient phenolic compounds followed by single m-diphenols. The effectiveness of these compounds was found to be related to their ability to trap rapidly the carbonyl compound, avoiding in this way the reaction of the carbonyl compound with the amino acid. The ability of flavan-3-ols for this reaction is suggested to be related to the high electronic density existing in some of the aromatic carbons of their ring A. This is the first report showing that carbonyl-phenol reactions involving lipid-derived reactive carbonyls can be produced more rapidly than carbonyl-amine reactions, therefore providing a satisfactory protection of amino compounds.

0217 : Antioxidant and protective effects of a pu-erh tea extract (camellia sinensis) on primary cultured rat cells

Oxidative stress is recognized to be implicated in the pathogenesis of cardiovascular and non-alcoholic fatty liver diseases. It is well know that tea is a rich source of phenolic compounds known for their antioxidant activity. Consequently, the antioxidant and protective effects of phenolic compounds from a pu-erh tea extract (PTE) was evaluated on primary culture of rat hepatocytes. PTE was quantified for its composition in catechins and polyphenol content by HPLC analysis. The antioxidant capacity of tea products was determined using TAC and DPPH assay methods. Then, antioxidant and hepatoprotective effects were determined by pretreating hepatocytes during 4h with various concentrations of PTE (25, 50 and 100μg/ml), epigallocatechin-3-gallate (EGCG) as major catechin of PTE (12μM corresponding to 100μg/ml PTE) and N-acetylcystein (NAC) (0.1 and 1mM) as an antioxidant reference. Then, cells were stressed for 1h with 150μM tert-Butyl hydroperoxide (TBHP). Viability was determined by real time cellular impedance and MTT assays. Oxidative stress was measured by CellRox, MitoSox and TMRE stainings and evaluated by fluorescence microscopy on an ArrayScanXTI high Content Analysis Reader (Cellomics Inc.). We found that TBHP induced oxidative stress (+1.5 fold increase vs control) was prevented by PTE pretreatment (+1.07 fold increase vs ctrl) and EGCG (+1.1 fold increase vs ctrl). We also demonstrated that PTE pretreatment protected rat hepatocytes (–28% mortality relative to TBHP) against TBHP induced mortality (+23% mortality relative to ctrl). However, EGCG did not prevented death in the same proportion than PTE (–9% mortality relative to TBHP). In this study, we reported that PTE pre-exposure prevented oxidative stress and mortality induced by TBHP. Moreover, we reported here that PTE has higher antioxidative and protective effects than EGCG alone, well known for its antioxidant effects, which means that EGCG may act in synergy with other PTE components.

In vitro toxicity assessment of silver nanoparticles in the presence of phenolic compounds – preventive agents against the harmful effect?

The increasing commercial use of silver nanoparticles (Ag-NPs) will inevitably lead to elevated silver exposure and thus to potential human health complications. In this study the acute toxicity of Ag-NPs <20 nm alone and upon co-administration with food matrix component phenolic compounds (PCs) on the cell-based models of the gastrointestinal tract was investigated. An improved co-culture model of Caco-2 and RajiB cells was applied for more precise in vitro simulation of the gastrointestinal tract. The involvement of two major factors contributing to the toxicity of Ag-NPs, i.e. the release of Ag+ and the induction of oxidative stress, was investigated. Ag-NPs were cytotoxic for Caco-2 cells with an EC50 of ca. 40 µg/ml. Ag-NPs led to oxidative stress starting from ca. 45 µg/ml. The epithelial barrier integrity disruption by Ag-NPs on Caco-2 cell mono- and co-cultures was established by decreased transepithelial electrical resistances and increased passages of Lucifer Yellow, a paracellular marker. Immunofluorescence staining demonstrated that Ag-NPs affect occludin and zonula occludens 1 distributions, suggesting the opening of tight junctions. Ag+, corresponding to the release from Ag-NPs, demonstrated a partial contribution in the toxic parameters, induced by Ag-NPs. Two PCs, quercetin and kaempferol, partially protected the Caco-2 cells from Ag-NP-induced toxicity and maintained the epithelial barrier integrity, disrupted by NPs. No protective effect was observed for resveratrol. The protective effect could be beneficial and decrease the potential toxicity of ingested Ag-NPs. However, the precise mechanisms of barrier-integrity-destabilising action of Ag-NPs/Ag+ and protective effect of PCs still require further elucidation.

Effect of Phenolic Compounds Against Aβ Aggregation and Aβ-Induced Toxicity in Transgenic C. elegans

Substantial evidence suggests that the aggregation of amyloid-β (Aβ) peptide into fibrillar structures that is rich in β-sheets is implicated as the cause of Alzheimer's disease. Therefore, an attractive therapeutic strategy is to prevent or alter Aβ aggregation. Phenolic compounds are natural substances that are composed of one or more aromatic phenolic rings and present in wine, tea, fruits, vegetables and a wide variety of plants. In this work, we investigated the effects of ferulic acid, morin, quercetin and gossypol against Aβ aggregation. From the ThT and turbidity assays, it is observed that in addition to the fibril aggregate, another type of aggregate is formed in the presence of morin, quercetin, and gossypol. On the other hand, ferulic acid did not prevent fibril formation, but it did appear to reduce the average length of fibrils compared to Aβ alone. To study the protective effects of phenolic compounds on Aβ-induced toxicity, we utilized the nematode Caenorhabditis elegans (C. elegans) as an in vivo model organism, human Aβ is expressed intracellularly in the body wall muscle. We found that exposure of Caenorhabditis elegans to ferulic acid give more protection against Aβ toxicity than morin, quercetin and gossypol.

The potential role of honey and its polyphenols in preventing heart diseases: a review.

Honey is rich in phenolic compounds, which act as natural antioxidants and are becoming increasingly popular because of their potential role in contributing to human health. A wide range of phenolic constituents is present in honey like quercetin, caffeic acid phenethyl ester (CAPE), acacetin, kaempferol, galangin which have promising effect in the treatment of cardiovascular diseases. Many epidemiological studies have shown that regular intake of phenolic compounds is associated with reduced risk of heart diseases. In coronary heart disease, the protective effects of phenolic compounds include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. In this review paper, we discussed the preventive role of polyphenols of honey against cardiovascular diseases.

Programmed cell death in plants: protective effect of phenolic compounds against chitosan and H2O2.

Addition of chitosan or H2O2 caused destruction of nuclei of epidermal cells (EC) in the epidermis isolated from pea leaves. Phenol, a substrate of the apoplastic peroxidase-oxidase, in concentrations of 10(-10)-10(-6) M prevented the destructive effect of chitosan. Phenolic compounds 2,4-dichlorophenol, catechol, and salicylic acid, phenolic uncouplers of oxidative phosphorylation pentachlorophenol and 2,4-dinitrophenol, and a non-phenolic uncoupler carbonyl cyanide m-chlorophenylhydrazone, but not tyrosine or guaiacol, displayed similar protective effects. A further increase in concentrations of the phenolic compounds abolished their protective effects against chitosan. Malate, a substrate of the apoplastic malate dehydrogenase, replenished the pool of apoplastic NADH that is a substrate of peroxidase-oxidase, prevented the chitosan-induced destruction of the EC nuclei, and removed the deleterious effect of the increased concentration of phenol (0.1 mM). Methylene Blue, benzoquinone, and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) capable of supporting the optimal catalytic action of peroxidase-oxidase cancelled the destructive effect of chitosan on the EC nuclei. The NADH-oxidizing combination of TMPD with ferricyanide promoted the chitosan-induced destruction of the nuclei. The data suggest that the apoplastic peroxidase-oxidase is involved in the antioxidant protection of EC against chitosan and H2O2.

Apoptosis induced by oxidized lipids is associated with up-regulation of p66Shc in intestinal Caco-2 cells: protective effects of phenolic compounds

In this study, we investigated the alterations of the redox balance induced by the lipid fraction of oxLDL in Caco-2 intestinal cells, and the effects of tyrosol and protocatechuic acid, two dietary phenolic compounds. We found that oxidized lipids extracted from oxLDL (LipE) induced oxidative stress by determining, 6 h after treatment, ROS overproduction (about a 100% and a 43% increase of O 2 − and H 2O 2 production, respectively, P<.05: LipE vs. control) and, 12 h after treatment, GSH depletion (about a 26% decrease, P<.05: LipE vs. control), and by impairing the activities of superoxide dismutase, catalase and glutathione peroxidase. In response to the induced oxidative stress, we observed significant overexpression of glutathione peroxidase (6 h after treatment: P<.05), glutathione reductase and γ-glutamylcysteine synthetase (12 h after treatment: P<.05). Notably, when GSH depletion occurred, p66Shc protein expression increased by about 300% with respect to control ( P<.001; LipE vs. control). These effects were fully counteracted by dietary phenolics which inhibited ROS overproduction and GSH consumption, rendered the reactive transcription of glutathione-associated enzymes unnecessary and blocked the intracellular signals leading to the overexpression and rearrangement of p66Shc signalling molecule. Altogether, these results suggest that the impairment of the antioxidant system hijacks intestinal cells towards an apoptotic-prone phenotype via the activation of p66Shc molecule. They also propose a reappraisal of dietary polyphenols as intestinal protecting agents, indicating the antiapoptotic effect as a further mechanism of action of these antioxidant compounds.

Protective Effects of Exogenous Antioxidants and Phenolic Compounds on Photosynthesis of Wheat Leaves under High Irradiance and Oxidative Stress

Infiltration of methyl viologen (MV, source of O2-) and Na-diethyldithiocarbamate (DDC, inhibitor of SOD) into wheat leaves resulted in the accumulation of active oxygen species and photo-oxidative damage to photosynthetic apparatus under both moderate and high irradiance. Exogenous antioxidants, ascorbate (ASA) and mannitol, scavenged active oxygen efficiently, protected the photosynthetic system from MV and DDC induced oxidative damage, and maintained high Fv/Fm [maximal photochemical efficiency of photosystem 2 (PS2) while all PS2 reaction centres are open], Fm/F0 (another expression for the maximal photochemical efficiency of PS2), ΦPS2 (actual quantum yield of PS2 under actinic irradiation), qP (photochemical quenching coefficient), PN (net photosynthetic rate), and lowered qNP (non-photochemical quenching coefficient) of the leaves kept under high irradiance and oxidative stress. Phenolic compounds used in these experiments, catechol (Cat), resorcinol (Res), and tannic acid (Tan), had similar anti-oxidative activity and protective effect on photosynthetic apparatus as ASA and mannitol. The anti-oxidative activity and the protective effect of phenolic compounds increased with increase in their concentration from 100 to 300 g m-3. The number and the position of hydroxyl group in phenolic molecules seemed to influence their antioxidative activity.

Protective effect of phenolic compounds isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death.

We isolated the phenolic compounds epicatechin, catechin, procyanidin B-1, procyanidin B-2, hyperin and caffeic acid from the hooks and stems of Uncaria sinensis (HSUS), and studied their protective effects against glutamate-induced neuronal death in cultured rat cerebellar granule cells. Cell viability evaluated by MTT assay was significantly increased by application of epicatechin (100-300 microM), catechin (300 microM), procyanidin B-1 (30-300 microM) and procyanidin B-2 (100-300 microM) compared with exposure to glutamate only. 45Ca2+ influx into cells induced by glutamate was also significantly inhibited by administration ofepicatechin (300 microM), catechin (300 microM), procyanidin B-1 (100-300 microM) and procyanidin B-2 (100-300 microM). These results suggest that epicatechin, catechin, procyanidin B-1 and procyanidin B-2 are the active components of HSUS that protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.

Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation.

The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra-virgin) and without (refined) phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025-0.3 mg/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper-mediated LDL oxidation in a concentration-dependent manner. Concentrations of phenolics greater than 20 mg/L inhibited formation of thiobarbituric-acid reactive substances after AAPH-initiated LDL oxidation. LDL isolated from plasma after preincubation with phenolics (25-160 mg/L CAE) showed a concentration-dependent increase in the lag time of conjugated diene formation after copper-mediated LDL oxidation. Refined olive oil (0 mg/L CAE) and extra-virgin olive oil (0.1 and 0.3 mg/L CAE) added to isolated LDL caused an increase in the lag time of conjugated diene formation after copper-mediated LDL oxidation that was related to olive oil phenolic content. Multiple regression analysis showed that phenolics were significantly associated with the increase in lag time after adjustment for effects of other antioxidants; alpha-tocopherol also achieved a statistically significant effect. These results indicate that olive oil phenolic compounds protect LDL against peroxyl radical-dependent and metal-induced oxidation in vitro and could associate with LDL after their incubation with plasma. Both types of olive oil protect LDL from oxidation. Olive oil containing phenolics, however, shows more antioxidant effect on LDL oxidation than refined olive oil.