Structure-antioxidant Activity Relationship Research Articles

Studies of the Relationship between Structure and Antioxidant Activity in Interesting Systems, Including Tyrosol, Hydroxytyrosol Derivatives Indicated by Quantum Chemical Calculations

In nature, tyrosol (TY) and hydroxytyrosol (HT) are found in olive leaves which are for medical aims, with immune stimulant and antibiotic properties as well as the ability to be used for the treatment of neurodegenerative diseases such as Alzheimer. This ability of phytochemical TY and HT compounds are mainly believed to be of higher radical scavenging potential with effective antioxidant properties. In order to establish the possible structure-antioxidant activity relationship of tyrosol, hydroxytyrosol, hydroxytyrosol acetate and two designed hydroxytyrosol derivatives were studied by the help of quantum chemical calculations. The molecular electronic properties such as heat formation of the neutral, radical and orbitals energies were calculated as descriptors to predict the H atom donating abilities of compounds. Considering the results from the calculated descriptors, the derivatives having OH group substitutions in position number four of the aromatic ring can be classified highly active and better antioxidant compound. Therefore, the designed hydroxytyrosol derivatives showed most active feasible H atom donation. This work can be useful to design novel antioxidants.

Characterization of structure–antioxidant activity relationship of peptides in free radical systems using QSAR models: Key sequence positions and their amino acid properties

Antioxidative peptides have attracted increasing attention from researchers because of their antioxidant properties as natural materials in functional food and for applications in medicine. However, the relationship between structure and activity (SAR) remains unclear, especially in antioxidative peptides in free radical systems. Antioxidative peptides with different lengths were obtained from the literature, measured using different methods, and were organized into three databases, namely, Trolox-equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and superoxide radical (SOR). After the peptides were processed using the two-terminal position numbering method, quantitative SAR modeling was performed on antioxidative peptides in the three databases. The vectors of hydrophobic, steric, and electronic properties (VHSE) and the divided physicochemical property scores descriptors (DPPS) were selected from 17 physicochemical descriptors to express electronic, hydrophobic, and steric properties (or hydrogen bonding) of the three (or four) external amino acids in the N-terminal and C-terminal positions. Models were estimated using partial least squares regression and validated through full cross-validation and external validation (R2>0.7, Q2>0.5 for TEAC; R2>0.9, Q2>0.5 for ORAC and SOR). The results found a relationship between the physicochemical properties of the C-terminal and N-terminal regions and antioxidant potency. The properties of amino acids at C-terminal regions were more important than those at the N-terminal regions for predicting antioxidant activity. The properties of amino acids at C2>C1 for TEAC, C3>C4>C1 for ORAC, and C4>C1>N1 for SOR were highly correlated with antioxidant activity. Although electronic property most significantly contributed to antioxidant activity in the three free radical systems, it had complex effects at each position. Bulky hydrophobic amino acids at the C-terminal were related to the antioxidant activity of peptides in the three free radical systems. For peptides in the TEAC database, the relationship between the N-terminal segment (N2, N3) and the activity increased when longer peptides were included, which reflects the likely influence of stericity. This study contributes to the ongoing research on antioxidants in food and its application in medicine.

Production and properties of chlorogenic acid lipophilic esters

AbstractChlorogenic acid is a dietary polyphenol with important bioactivities. However, its high hydrophilicity prevents its applications as an antioxidant for lipid protection in a complex matrix such as food. Grafting an aliphatic chain onto chlorogenic acid, so‐called lipophilisation, via lipase‐catalysed esterification represents an efficient means of increasing its lipophilicity. A series of alkyl esters with various chain lengths were produced and used to explore the structure‐antioxidant activity relationship of amphiphilic antioxidants. Data obtained from complex systems (oil‐in‐water emulsion and cell culture) concluded that short or medium chain lengths enhance the antioxidant activity while longer chains tend to decrease the antioxidant ability of chlorogenic acid. This phenomenon remains to be fully explained. Acyl esters, in which the carboxylic acid group remains free were also produced and were shown to be interesting antioxidant candidates as well as useful tools for the understanding of antioxidant activities.

Highly glycosylated and acylated flavonols isolated from kale (Brassica oleracea var. sabellica) — Structure–antioxidant activity relationship

Kale is a common Brassica vegetable rich in secondary plant metabolites especially flavonols, that comprise highly glycosylated and acylated quercetin and kaempferol derivatives. Several kale flavonols have been isolated, structurally identified and characterized by means of HPLC-DAD-ESI–MSn and NMR spectroscopy from kale for the first time. Their antioxidant activity given by a wide variety of glycosylation and acylation patterns was investigated using the Folin–Ciocalteu assay, the TEAC assay, and EPR spectroscopy. The purpose was to obtain distinct structure–antioxidant activity relationships of structures differing either in their aglycone structure, their number of glycoside substituent, and the kind of acylation. A high radical scavenging activity is mainly due to catechol like structure of e.g. quercetin derivatives. Noteworthy is the fact that flavonol derivatives esterified with methoxylated hydroxycinnamic acids possess higher antioxidant capacities than those conjugated with hydroxycinnamic acids with catechol structure. Remarkably, the influence of the acyl moiety seems to be less effective than that of the glycosylation pattern in 7-O position. In conclusion, the antioxidant behavior differs depending on the assay used and the above mentioned structural features, revealing the importance of these attributes to be responsible for a specific antioxidant capacity.

Quantitative Structure-Antioxidant Activity Relationship of Quercetin and its New Synthetised Derivatives

Interest in the biological activity of the flavonoids increases due to the potential health benefits of these polyphenolic components of foodstuff. Our research investigates biological properties of the flavonoids and their new synthetized derivatives, focuses on the relationship between their antioxidant activity and their chemical structures. Quantitative structure-activity relationship (QSAR) attempts to correlate chemical structure with biological activity using statistical approaches. It is the process by which chemical structure of a molecule is quantitatively correlated with a well defined process, such as biological activity, that can be expressed quantitatively as the concentration of a substance required to give a certain biological response. When physicochemical properties or structures are expressed by numbers, the mathematical relation can be formed between the two. The mathematical expression can then be used to predict the biological response of other chemical compounds. QSARs represent predictive models derived from application of statistical tools correlating antioxidant activity (including desirable therapeutic effect and undesirable side effects) of chemicals with descriptors representative of molecular structure and properties. Obtaining a good QSAR model depends on many factors, such as the quality of biological data, the choice of descriptors and statistical methods. Any QSAR modeling should ultimately lead to statistically robust models capable of making accurate and reliable predictions of biological activities of new untested compounds.

Theoretical and experimental studies on the structure-antioxidant activity relationship of synthetic 4-methylcoumarins

The development of antioxidants as useful drugs for the treatment of neurodegenerative diseases such as Alzheimer’s is extremely challenging in medicinal chemistry. Coumarins have attracted great attention as possible therapeutic tools against oxygen radicals in human degenerative diseases. In order to establish the possible structure-antioxidant activity relationship, a series of twenty four 4-methylcoumarin derivatives were examined by employing reducing power measurements, and comparison with bond dissociation enthalpy and ionization potential calculations. Based on the reducing potency of 4-methylcoumarin derivatives with respect to trolox, these compounds were classified into five groups as “most active”, “more active”, “moderately active”, “less active” and “inactive” derivatives. The presence of hydroxyl groups is an essential requirement for the activity, and substitution of hydroxyl groups by methoxy groups leads to non-active derivatives. The results revealed that dihydroxyl groups in the ortho position show a better antioxidant activity with respect to dihydroxyl groups in the meta position. This is ascribed to the ability to construct more stable 4-methylcoumarin radical intermediates by rearrangement of intra-molecular hydrogen bonding. Our findings indicate that other important factors to enhance the antioxidant activity of coumarins are the number of hydroxyl groups, the presence of ester substitutions and a thiono functional group on the pyrone ring. However, bond dissociation enthalpy and ionization potential calculations alone are not sufficient to identify the best antioxidant structures. As a result, chemical and functional properties of molecules such as 4-methylcoumarins should be examined as a whole entity, considering all substitutions versus a single substitution to design functional compounds with good antioxidant activity.

Structure–antioxidant activity relationship study of natural hydroxybenzaldehydes using in vitro assays

Structure–activity relationships (SARs) were sought among protocatechuic aldehyde 1, syringaldehyde 2, vanillin 3, p-hydroxybenzaldehyde 4 and salicylaldehyde, 5 using various in vitro antioxidant assays (crocin bleaching assay, ABTS, DPPH, Rancimat and liposomes). These aldehydes are known to contribute to the evolution of flavor during aging of alcoholic beverages in wood barrels and as natural preservatives. Their acid counterparts (1′–5′) were also studied for comparison. The non-substituted hydroxybenzaldehydes (4, 5) and the respective acids showed negligible activity under the CBA, DPPH and the accelerated bulk oil oxidation conditions, so that no SAR could be drawn. The only compound that exhibited high antioxidant activity, equal or even higher than 1′, in all assay environments was 1. Syringaldehyde was found to possess exceptionally high activity in comparison to 2′, only under the CBA conditions. Moreover, 1 and 2 were found to be strong inhibitors of bulk oil or of lecithin liposome oxidation. Our findings add to knowledge about the antioxidant activity of the particular aldehydes apart from their flavoring and antibacterial properties.

Quantum-chemical study on the antioxidation mechanisms of trans-resveratrol reactions with free radicals in the gas phase, water and ethanol environment

To explain the structure–antioxidant activity relationships of trans-resveratrol, its anions and phenoxy radical in the gas phase, water and ethanol media, the quantum-chemical calculations based on CPCM solvation model have been performed for the first time. For fully optimised geometries, the antioxidative parameters have been calculated at the B3LYP/6-311G(d,p) and B3LYP/6-311+G(d,p) levels of theory. The calculated values of the Gibbs free enthalpies revealed that the reactions of trans-resveratrol with water molecule are thermodynamically unfavourable, while the reaction of this compound with hydroxide anion is thermodynamically preferable in the media studied. The calculations performed have shown that in polar media, the 4′-OH group is a stronger proton donor than the 3-OH group and hence, the 4′-OH group contributes most to the antioxidant activity of trans-resveratrol. In addition, it has been established that the ability of 4′-O-monoanion to donate proton is higher than that of 3,4′-O-dianion and 3,5-O-dianion of trans-resveratrol in the media investigated. The results obtained demonstrate that the hydrogen atom transfer mechanism for scavenging of free radicals is more preferable than the single-electron transfer or the sequential proton loss electron transfer mechanism in all types of environment. Trans-resveratrol is found to be a more active donor of hydrogen atoms in the gas phase than in polar environments and in polar media it is more susceptible to electron and proton donation than in the gas phase. Polar media are shown to stabilise trans-resveratrol and its 4′-O-radical, cation radical and all anionic forms stronger than the gas phase. Furthermore, our study shows that the antioxidant capacity of trans-resveratrol is related to the planar and semi-quinone structure of its 4′-O-radical and all anionic forms in the environments investigated.

Development and validation of a chemiluminogenic method for the evaluation of antioxidant activity of hydrophilic and hydrophobic antioxidants

A sensitive and simple procedure is described for evaluating the antioxidant activity of 21 known hydrophilic and hydrophobic compounds by using the chemiluminogenic reaction of lucigenin with hydrogen peroxide. The method was validated for linearity, limit of detection, precision, additivity and ruggedness and compared to the DPPH method. Furthermore, the IC 50 values of all compounds were calculated and compared by both methods and results are discussed on the basis of structure–antioxidant activity relationship. Among hydrophilic antioxidants, phenolic compounds with adjacent hydroxyl groups (gallic acid, caffeic acid, pyrocatechol, (±)-catechin, oleuropein) were found to be efficient antioxidants in chemiluminescence method with IC 50 values at the sub-micromolar range, while phenolic compounds without adjacent hydroxyl groups (p-coumaric acid, BHT, BHA, resorcinol) exhibited weak activity with IC 50 values > 10 μM. α-Tocopherol was the most efficient hydrophobic antioxidant (IC 50 = 6.7 μM) while oleic and linoleic acids were found to be very poor antioxidants (IC 50 > 300 μM). Finally the method was applied to the estimation of antioxidant activity of complex samples such as olive oils. To the best of our knowledge, this is the first time that total antioxidant activity can be determined directly in olive oil and not in aqueous extracts.

Plant extracts with anti-inflammatory properties—A new approach for characterization of their bioactive compounds and establishment of structure–antioxidant activity relationships

Geranium robertianum L. (Geraniacea) and Uncaria tomentosa (Willd.) DC. (Rubiaceae) plant extracts, frequently used in traditional medicine for treatment of inflammatory and cancer diseases, were studied to identify potential bioactive compounds that may justify their therapeutic use and their underlying mechanisms of action. Since some of the pharmacological properties of these plant extracts may be linked to their antioxidant potential, the antioxidant activity, in relation to free radical scavenging, was measured by the ABTS/HRP and DPPH assays, presenting U. tomentosa the higher activity. The antioxidant activity was also evaluated by scavenging of HOCl, the major strong oxidant produced by neutrophils and a potent pro-inflammatory agent. U. tomentosa was found to be a better protector against HOCl, which may justify its effectiveness against inflammatory diseases. SPE/LC-DAD was used for separation/purification purposes and ESI-MS/MS for identification/characterization of the major non-volatile components, mainly flavonoids and phenolic acids. The ESI-MS/MS methodology proposed can be used as a model procedure for identification/characterization of unknowns without the prerequisite for standard compounds analysis. The ESI-MS/MS data obtained were consistent with the antioxidant activity results and structure–activity relationships for the compounds identified were discussed.

Structure–Antioxidant Activity Relationships in a Series of NO‐Donor Phenols

Recently we reported a new class of NO-donor phenols that could be of interest in the treatment of many forms of cardiovascular disease (CD). Their potencies as inhibitors of ferrous salt/ascorbate-induced peroxidation of membrane lipids of rat hepatocytes were assessed as pIC(50) values through the TBARS assay. In this work we aimed to find quantitative relationships between the antioxidant activity of these compounds and appropriate molecular descriptors. In particular, we determined their log P(oct), their reactivity (log Z) in reaction with the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(.)), and the theoretical parameter DeltaH(abs), which describes the enthalpy of homolytic O--H bond cleavage. The QSAR equations found through the classical Hansch approach allowed us to draw interesting conclusions on the possible mechanisms of reaction with radicals in the various environments, while underlining the role of lipophilicity in antioxidant activity.

Soil Quality Effects on Chenopodium album Flavonoid Content and Antioxidant Potential

Antioxidant capacity, total phenolic content and flavonoid glycosides profile were compared in C.album samples grown in intensively cultivated (IC) and nondisturbed (ND) soils to evaluate differences in their nutraceutical potential. Petroleum ether, methanol, and aqueous extracts were sequentially obtained from C. album dried samples. Methanol crude extract exhibited the highest antioxidant potential and phenolic content, which were significantly enhanced by soil deterioration. This feature was enhanced in its ethyl acetate/n-buthanol subextract that also yielded higher amounts of the fraction containing flavonoid glycosides in samples grown in IC soils. Compounds were isolated by activity guided fractionation, and chemical structure-antioxidant activity relationships were established. Chemical structures were elucidated by chemical and spectroscopic methods. Six known flavonoid glycosides were isolated, and their antioxidant activity was determined by DPPH assay. 1, quercetin-3-O-(2",6"-di-O-R-L-rhamnopyranosyl)-beta-D-glucopyranoside; 2, kaempferol-3-O-(2",6"-di-O-R-L-rhamnopyranosyl)-beta-D-glucopyranoside; 3, quercetin-3-O-beta-D-glucopyranosyl-(1'''-->6")-beta-D-glucopyranoside; 4, rutin; 5, quercetin-3-O-beta-D-glucopyranoside; and 6, kaempferol-3-O-beta-D-glucopyranoside. Triosides 1 and 2 were identified for the first time in C. album. Our results suggest that this edible weed, ubiquitously present in cultivated fields, should be considered as a nutraceutical food and an alternative source for nutrients and free radical scavenging compounds, particularly when collected from cultivated fields that seem to increase some of its advantages.

Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats

Flavonoids are known to possess a broad set of pharmacological effects, some of which have been attributed to their antioxidant properties and, more recently, to cell signalling modulation. Nevertheless, flavonoids are extensively metabolized and their metabolites are the potential bioactive forms in vivo. Therefore, a first and crucial step to understand the mechanisms underlying potential health benefits of flavonoids is knowledge of their metabolites and their biological activities. To approximate a human dietary pattern of intake of flavonoids, regular rat chow was supplemented with 0.02% quercetin and fed to Sprague-Dawley rats over 3 weeks. Plasma samples were analysed by HPLC and electrospray tandem mass spectrometry, and plasma antioxidant capacity was measured by the 2,2'-azino-bis(3-ethylbenzothiazoline sulphonate) assay. Major metabolites were 3'-methylquercetin (isorhamnetin) glucuronide sulphate conjugates, the most plausible conjugation positions being at the 3-, 5- and 7-hydroxyl positions. Isorhamnetin conjugates are methylated at the 3'-OH position, which decreases the high antioxidant activity of quercetin and its metabolites and their contribution to plasma antioxidant potential. This metabolic pattern differs from that observed after a single high-dose administration, where the major metabolites were quercetin conjugates at 5- and 7-hydroxyl positions and a significantly increased plasma antioxidant activity was observed. These data show altogether that the different metabolic patterns obtained under a prolonged low-dosage regimen or after a single high dose, crucially affected the antioxidant potential of plasma in treated animals. Our data also allow for the establishment of structure-antioxidant activity relationships for quercetin metabolites.

Synthesis, antioxidant activity and structure–activity relationships for a new series of 2‐(N‐acylaminoethyl)indoles with melatonin‐like cytoprotective activity

5-Methoxy-2-(N-acetylaminoethyl)indole (5d), a melatonin analogue derived from the transposition of the acetylaminoethyl side chain from C3 to C2 of the indole nucleus, had been previously characterized as a low affinity antagonist at MT1 and MT2 membrane receptors; this molecule is endowed with good in vitro antioxidant and cytoprotective potency in rat cerebellar cell cultures, comparable to or better than those of melatonin. In order to further investigate the role of structure-antioxidant activity relationships in cytoprotection, the structure of 5d was systematically modulated to design a new series of compounds. The 5-methoxy group was replaced by substituents with different electronic and lipophilic properties and it was moved to a different position on the indole ring. Other modifications of the lead structure involved the methylation of the indole nitrogen or its replacement by a sulfur atom. The side chain was also modified either increasing its lipophilicity or introducing an ionisable acid group. The antioxidant activity of this set of compounds was evaluated by the ABTS and conjugated dienes (CD) assays, while their cytoprotection was evaluated against kainate-induced cytotoxicity in cultured cerebellar neurons. In both antioxidant assays, the shift of the 5-methoxy group to the 4-position of the indole nucleus led to the most active radical scavenger (9), more potent than the parent compound and melatonin in the antioxidant tests, but much less effective as a cytoprotectant. Sharp structure-activity relationships were registered for cytoprotection, where the maintenance of the 5-alkoxy-2-(N-acylaminoethyl)indole scaffold appeared as the key feature to confer both antioxidant and cytoprotective activity to the structure. Some derivatives of the set, however, together with the most potent 5d, maintained a significant antioxidant and cytoprotective effect and could be employed as tools for in vivo pharmacological investigations on neuroprotective efficacy of melatonin-related indoles.

Molecular Dynamics Simulations on the Coplanarity of Quercetin Backbone for the Antioxidant Activity of Quercetin-3-monoglycoside

Flavonoids are a broad class of low molecular weight, secondary plant phenolics characterized by the flavan nucleus. The family includes flavanols, flavanones, anthocyanidines, flavones, and flavonols. Most of the beneficial effects of flavonoids are attributed to their antioxidant abilities. The flavonoids contain a number of phenolic hydroxyl groups attached to ring structures, conferring the antioxidant activity. Among these flavonoid families, flavonols are found in almost every plant. The most commonly occurring flavonols are those with dihydroxylation in the 3' and 4' positions of B ring and the preferred glycosylation site on the flavonoids is the 3 position. It has been reported that the hydroxyl group at position 3 is required for the maximal radical scavenging activity of flavonols. Quercetin is a representative flavonol with high antioxidant activity. Therefore, we focused on the conformation of quercetin and quercetin-3-monoglycoside to investigate the effect of glycosylation of quercetin on their antioxidant activity. Structure-antioxidant activity relationships of flavonoids have been extensively reported. Generally, antioxidant activity depends on the number and positions of hydroxyl groups and other substituents, and glycosylation of flavonoid molecules. Glucose is the most usual sugar residue but others include galactose and rhamnose. Aside from other factors which can affect the activity, it is generally known that glycosylation of flavonoids diminishes their antioxidant activity when compared to the corresponding aglycones, perhaps since this reduces the number of free hydroxyl groups and also the linkage of sugar may hinder access of the free radical scavengers to the radical center. As mentioned above, there are several and complicated factors which affect the antioxidant activity of flavonol. Conjugation between the Aand B-rings permits a resonance effect of the aromatic nucleus that lends stability to the flavonoid radical. van Acker et al. suggested that the removal of the 3 hydroxyl group or other substituents interfere with the coplanarity of the B-ring with the rest of the flavonoid and the ability to delocalize electrons. They calculated the geometry using quantum chemical calculation which cannot include the solvent effects and shows only optimized conformation. The flavonols are conformationally flexible and their conformations are influenced by the intermolecular environment. Thus, a range of torsion angle of backbone can be observed for the same flavonol in different environments. Therefore, we pursue the trajectories during the molecular dynamics simulations in aqueous environment and investigate the coplanarity of quercetin’s backbone and conformations in order to find out the relationship between the conformation and antioxidant activity. It is difficult to compare the antioxidant activities of flavonols between the results of one author and others because of different experimental condition, methods, and skill. Therefore, we selected one reference which use two different methods and obtained similar results. Six flavonols are investigated by molecular dynamic simulations and their chemical structures and abbreviations are shown in Figure 1. Quercetin aglycone has the most potent antioxidant activity in flavonol aglycones. The structure of quercetin was elucidated by crystal and molecular modeling. The exocyclic B ring of quercetin exists in an almost planar conformation with respect to the rest of the molecule. Quercetin not only has 3-hydroxyl group in the C-ring and 3',4'-dihydroxy groups in the B-ring, but also possess the 2,3-double bond in conjugation with 4-oxo function in the C-ring (Figure 1), which are the essential structural elements for potent radical

Antioxidant profile of dihydroxy- and trihydroxyphenolic acids-A structure–activity relationship study

Eight structurally similar dihydroxy and trihydroxyphenolic acids (protocatechuic acid, 3,4-dihydroxyphenylacetic acid, hydrocaffeic acid, caffeic acid, gallic acid, 3,4,5-trihydroxyphenylacetic acid, 3-(3,4,5-trihydroxyphenyl)propanoic acid and 3-(3,4,5-trihydroxyphenyl)propenoic acid) were examined for their total antioxidant capacity (TAC). Furthermore, their ability to scavenge peroxyl radicals, generated by AAPH in liposomes, was determined. The antioxidant/pro-oxidant activity of the compounds was screened using the 2′-deoxyguanosine assay. All compounds behave as radical scavengers, with 3,4,5-trihydroxyphenylacetic acid being the most potent. Nevertheless, in the lipid peroxidation assay an inverse ranking order was observed, 3,4-dihydroxyphenylacetic acid being the most effective compound. All the dihydroxylated compounds showed a pro-oxidant behaviour leading to an increase of 50% in 8-OH-dG induction. From the structure–antioxidant activity relationship studies performed it may be concluded that the number of phenolic groups and the type of the alkyl spacer between the carboxylic acid and the aromatic ring strongly influence the antioxidant activity.

Superoxide radical- and peroxynitrite-scavenging activity of anthocyanins; structure-activity relationship and their synergism

Antioxidant activities of 15 purified bilberry anthocyanins together with pelargonidin 3-O-β-d-glucopyranoside and 4′-O-methyl delphinidin 3-O-β-d-glucopyranoside (MDp 3-glc), the major metabolite of delphinidin 3-O-β-d-glucopyranoside (Dp 3-glc), were evaluated in order to study the structure-antioxidant activity relationship and any synergism among them in the mixture. Both aglycone structure and the attached sugar moiety affected the - and ONOO− -scavenging activities, although the effect of the attached sugar moiety was smaller than that of the aglycone structure. The potency of activity toward the superoxide radical was in the following order: delphinidin > petunidin > malvidin ≈ cyanidin>(+)-catechin > peonidin > pelargonidin. The activity toward ONOO− was: delphinidin > cyanidin ≈ petunidin > malvidin ≈ (+)-catechin > peonidin > pelargonidin. It was confirmed that methylation of 4′-OH markedly reduced the antioxidant activity of anthocyanin. Further, it was revealed that synergism occurred in both - and ONOO− -scavenging activities among the anthocyanins in the mixture.

Structure–activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives

Gallic acid and its derivatives are a group of naturally occurring polyphenol antioxidants which have recently been shown to have potential healthy effects. In order to understand the relationship between the structures of gallic acid derivatives, their antioxidant activities, and neuroprotective effects, we examined their free radical scavenging effects in liposome and anti-apoptotic activities in human SH-SY5Y cell induced by 6-hydrodopamine autooxidation. It was found that these polyphenol antioxidants exhibited different hydrophobicity and could cross through the liposome membrane to react with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical in a time and dose-dependent manner. At the same time, the structure–antioxidant activity relationship of gallic acid derivatives on scavenging DPPH free radical in the liposome was also analyzed based on theoretical investigations. Analysis of cell apoptosis, intracellular GSH levels, production of ROS and the influx of Ca 2+ indicated that the protective effects of gallic acid derivatives in cell systems under oxidative stress depend on both their antioxidant capacities and hydrophobicity. However, the neuroprotective effects of gallic acid derivatives seem to depend more on their molecular polarities rather than antioxidant activities in the human SH-SY5Y cell line. In conclusion, these results reveal that compounds with high antioxidant activity and appropriate hydrophobicity are generally more effective in preventing the injury of oxidative stress in neurodegenerative diseases.

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.

Potential of Eigen Value Method to the Study on Structure‐antioxidant Activity Relationship

AbstractAntioxidants are of great interest because of their involvement in many important biological and industrial processes. It is meaningful to study their structure‐antioxidant activity relationship (SAAR) and design novel, efficient and low‐toxicity antioxidant. In this paper, Eigen Value Analysis (EVA), a 3‐dimensional quantitative structure activity relationship (3‐D QSAR) method, was employed to study antioxidant SAAR. Significant relational models were obtained with all the PLS cross‐validate $q^{2}_{cv} $ values being larger than 0.5, meaning that the models have sound predictive power. Compared with other QSAR methods, EVA possesses several advantages, especially that it does not need alignment. It should be believed that EVA will be an efficient approach to SAAR.