Synergistic, additive, and antagonistic antioxidant effects in the mixtures of curcumin with (-)-epicatechin and with a green tea fraction containing (-)-epicatechin.

The combinations of curcumin with green tea flavan-3-ols produce various synergistic biological effects. This study aimed to verify the antioxidant effects in mixtures of curcumin with (-)-epicatechin (EC) or with EC fraction from green tea in a non-polar lipid system (triacylglycerol autoxidation) and in a polar conditions (ABTS assay). Curcumin was 2.5-2.6 and 2.9-3.6 times weaker antioxidant than EC and EC fraction, respectively. The synergism was found in mixtures using the isobologram analysis of ABTS•+ scavenging activity results. The strongest effect with a combination index of 0.751 was in the equimolar mixture of pure compounds. In the lipid system, antagonism occurred for curcumin and EC fraction combination. However, an additive effect was found between curcumin and EC. In conclusion, the antioxidant effects in the curcumin and EC mixtures depended on the polarity of the assay media, the ratio of antioxidants, and presence other phenolics in the system.

Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress.

Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon "tails" of the lipids. This process is known as "lipid peroxidation", and the accumulation of the oxidation products as peroxides and the aldehydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like ortho-methoxy and ortho-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure-activity relationship ((Q)SAR) modeling) were used to clarify their structure-activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed.

Antioxidant properties of novel curcumin analogues: A combined experimental and computational study.

The multi-target activity of curcumin makes it a promising pharmacological lead for structural modifications focused on the preparation of new better therapeutics with improved bioavailability. A possible modification is to "decompose" the parent curcumin structure into constituent units and to build up curcumin analogues with biphenyl structural moiety. The antioxidant properties of the so-called "monomers" (m1-m3) and "dimers" (d1-d3) are studied experimentally and computationally. Their protective effects as chain-breaking antioxidants are investigated for the individual compounds and in binary/ternary compositions with α-tocopherol (TOH) and ascorbyl palmitate (AscPH). All monomers manifest significant synergism up to 70% in mixtures with TOH. Synergistic effects are found for the ternary compositions of monomeric analogues upon addition to the binary mixture of standard antioxidants (TOH + AscPH). Dimers with biphenyl skeleton manifest a lower potential in compositions under lipid oxidation conditions. DFT computations provide a detailed insight into the structure and antiradical properties of the curcumin analogues and standard antioxidants. PRACTICAL APPLICATIONS: Bioactive compounds in the diet play a crucial role in the prevention of numerous diseases in whose pathogenesis oxidative stress is well known to be involved. Therefore, enhancement of the antioxidant status of the biological target is often helpful. Two of the monomers studied are considered leading agents in the treatment or prophylaxis of smooth muscle disorders and are useful in the maintenance of the normal gut function- as a calmative for the gut and to ease upset stomach. We hypothesized that the presence of a biphenyl scaffold in the parent molecular structure can enhance the biological activity. Equimolar mixtures of TOH with studied compounds have potential application in food chemistry and medicine. A composition comprising the active agent and additional components (strong conventional antioxidants) may be administered in foodstuffs, as a food supplement, beverage supplement, or as a pharmaceutical composition.

Protective effects of new antioxidant compositions of 4-methylcoumarins and related compounds with dl-α-tocopherol and l-ascorbic acid.

BACKGROUND: Coumarin derivatives possess a wide range of biological activities. By functionalization of the parent coumarin skeleton that has neither antioxidant nor biological activity, a series of new bio-antioxidants has been designed. RESULTS: New antioxidant compositions (equimolar binary and ternary mixtures) of eight 4-methylcoumarins and three related compounds have been tested and different effects between individual components have been observed: synergism (positive effect), additivism (summary effect) and antagonism (negative effect). Higher oxidative stability of the lipid substrate was obtained in the presence of the new antioxidant compositions of the studied compounds with dl-α-tocopherol and l-ascorbic acid. The role of each component in the antioxidant compositions of ternary mixtures has been identified by using new equations composed by the authors. CONCLUSION: All ternary mixtures demonstrate synergism as a result of continuous regeneration of dl-α-tocopherol from the studied antioxidants and l-ascorbic acid. Theoretical calculations have been probed as indicators of the expected effects between the individual components in a binary mixture. © 2018 Society of Chemical Industry.

Protective effects of 4-methylcoumarins and related compounds as radical scavengers and chain-breaking antioxidants.

The aim of this study is to determine, and to compare the protective effects of eight 4-methylcoumarins and four related compounds as radical scavengers and chain-breaking antioxidants. The main kinetic parameters of their radical scavenging activity (as % RSA, stoichiometry, n, and rate constants of reaction with DPPH radical, kRSA) and of chain breaking antioxidant activity (as antioxidant efficiency, PF and reactivity, ID), have been determined and discussed. The RSA study has been conducted at physiological temperature (37 °Ð¡) towards DPPH radical and the tested compounds are separated into three main groups: with strong activity (% RSA > 40%); with moderate activity (20% < % RSA > 40%) and with weak activity (% RSA < 20%). Chain-breaking antioxidant activities of the studied compounds have been evaluated during bulk phase lipid (triacylglycerols of sunflower oil, TGSO) autoxidation at 80 °C. All results obtained are compared with those for standard and known inhibitors of oxidation processes, e.g. caffeic and p-coumaric acids, α-tocopherol and butylated hydroxytoluene (BHT). On the basis of a comparative analysis with standard antioxidants, the differences in the radical scavenging and antioxidant abilities of the studied compounds have been discussed and reaction mechanisms proposed. All structures are optimized at UB3LYP/6-31 + G(d,p) level in gas phase and in acetone solution to study the solvation effects.

Effects of Gamma-Irradiation on the Antioxidant Potential of Traditional Bulgarian Teas.

Food irradiation technologies are used to reduce the risk of food bome diseases by eliminating pathogenic microorganisms, prolonging shelf life and reducing storage losses by delaying ripening, germination or sprouting. However, application of irradiation in food technology can negatively influence the biologically active compounds in foods. In this research, the effect of gamma-irradiation on the antioxidant activity of Bulgarian teas was investigated. The aim of the study was to evaluate the total phenolic and tannin content and antioxidant activity of ethanolic extracts of Bulgarian herbal teas before and after gamma-irradiation. Mursalski tea (Sideritis scardica), Mashterka tea (Thymus serpyllum), Good Night tea (tea mix), Staroplaninski tea (Balkan tea mix), Trakia tea (tea mix), and Mountain tea (Planinski tea mix) were selected for this study. Gamma-irradiation was applied at the absorbed dose of 5 kGy. Antioxidant activity of non- irradiated and irradiated teas was determined by measuring antiradical activity against DPPH' and ABTS and the ability to reduce ferrous ions. The highest total-phenolic content was found in Mursalski tea (268 mg/g), and the highest tannin content in Good Night tea (168 mg/g). FRAP, TEAC and DPPH assays revealed that the most active samples were Staroplaninski (2.78 mmol Fe (II)/g), Planinski (0.87 mmol Trolox/g) and Planinski (0.032 mg/mL), respectively. The radical scavenging activity of irradiated tea samples was maintained after gamma-irradiation. The most interesting extract from irradiated tea studied was Staroplaninski, which demonstrated a higher antioxidant potential in the irradiated sample compared with the non-irradiated sample.

Kinetics of curcumin oxidation by 2,2-diphenyl-1-picrylhydrazyl (DPPH˙): an interesting case of separated coupled proton-electron transfer.

The decay of dpph˙ in absolute ethanol at 25 °C and in the presence of curcumin (1), 4-methylcurcumin (3), 4,4-dimethylcurcumin (4) or curcumin 4'-methyl ether (5) follows bi-exponential kinetics. These unusual reaction kinetics are compatible with a two-step process in which an intermediate accumulates in a reversible first step followed by an irreversible process. As in other similar cases (Foti et al., Org. Lett., 2011, 13, 4826-4829), we have hypothesised that the intermediate is a π-stacked complex, formed between one curcumin anion (in the case of 1, 3 and 5 the enolate anion) and the picryl moiety of dpph˙, in which an intra-complex electron transfer from the (enolate) anion takes place. By comparing the kinetics of curcumin 4',4''-dimethyl ether (2) (no phenolic OH), (5) (one phenolic OH) and (1) (two phenolic OHs), we have deduced that the electron transfer process must be accompanied by a simultaneous proton transfer from the phenolic OHs to the bulk solvent (separated coupled proton-electron transfer). The rate constants kα for the forward reaction of 2, 5 and 1 with dpph˙ are in fact ∼0, 7.5 × 10(3) and 1.8 × 10(4) M(-1) s(-1), respectively, in a clear dependence on the number of phenolic OHs.

Antioxidant Activity of Flaxseed Extracts in Lipid Systems.

The aim of this work was to compare the antioxidant activity of the extract of flaxseed and its alkaline hydrolysate in two model systems: lipid autoxidation of triacylglycerols of sunflower oil (TGSO)-in a homogeneous lipid media and during ß-carotene-linoleate emulsion system. In addition, pure lignans were tested. The material was defatted with hexane and then phenolic compounds were extracted using dioxane-ethanol (50:50, v/v) mixture. Carbohydrates were removed from the crude extract using an Amberlite XAD-16 column chromatography. The content of total phenolic compounds in the crude extract and after alkaline hydrolysis was determined using a Folin-Ciocalteu's phenol reagent. Individual phenolic compounds were determined by nordihydroguaiaretic acid (RP-HPLC) method in gradient system. The alkaline hydrolysis increased the content of total phenolics in the extract approximately by 10%. In the extracts of flaxseed, phenolic compounds were present in the form of macromolecular complex. In the alkaline hydrolysate, secoisolariciresinol diglucoside (SDG) was found as the main phenolic compound. Small amounts of p-coumaric and ferulic acids were also determined. SDG and both extracts were not able to inhibit effectively lipid autoxidation. The kinetics of TGSO autoxidation at 80 °C in absence and in presence of the extract before hydrolysis (EBH) and after hydrolysis (EAH) was monitored and compared with known standard antioxidants. Ferulic acid (FA) and butylated hydroxyl toluene (BHT) showed much higher antioxidant efficiency and reactivity than that of both extracts. Secoisolariciresinol (SECO) showed a higher activity in both model systems than SDG. However, the activity of SECO was much lower than that of nordihydroquaiaretic acid (NDGA).

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations.

This study compares the ability to scavenge different peroxyl radicals and to act as chain-breaking antioxidants of monomers related to curcumin (1): dehydrozingerone (2), zingerone (3), (2Z,5E)-ethyl 2-hydroxy-6-(4-hydroxy-3-methoxyphenyl)-4-oxohexa-2,5-dienoate (4), ferulic acid (5) and their corresponding C 2-symmetric dimers 6-9. Four models were applied: model 1 - chemiluminescence (CL) of a hydrocarbon substrate used for determination of the rate constants (k A) of the reactions of the antioxidants with peroxyl radicals; model 2 - lipid autoxidation (lipidAO) used for assessing the chain-breaking antioxidant efficiency and reactivity; model 3 - oxygen radical absorbance capacity (ORAC), which yields the activity against peroxyl radicals generated by an azoinitiator; model 4 - density functional theory (DFT) calculations at UB3LYP/6-31+G(d,p) level, applied to explain the structure-activity relationship. Dimers showed 2-2.5-fold higher values of k A than their monomers. Model 2 gives information about the effects of the side chains and revealed much higher antioxidant activity for monomers and dimers with α,ß-unsaturated side chains. Curcumin and 6 in fact are dimers of the same monomer 2. We conclude that the type of linkage between the two "halves" by which the molecule is made up does not exert influence on the antioxidant efficiency and reactivity of these two dimers. The dimers and the monomers demonstrated higher activity than Trolox (10) in aqueous medium (model 3). A comparison of the studied compounds with DL-α-tocopherol (11), Trolox and curcumin is made. All dimers are characterized through lower bond dissociation enthalpies (BDEs) than their monomers (model 4), which qualitatively supports the experimental results.

Protective effects of equimolar mixtures of monomer and dimer of dehydrozingerone with α-tocopherol and/or ascorbyl palmitate during bulk lipid autoxidation.

Protective effects of recently synthesised dehydrozingerone, M1OH (which is one half of the molecule of curcumin) and dimer of dehydrozingerone, D1(OH)2, as individual compounds (1 mM) and as equimolar binary (1:1) and ternary (1:1:1) mixtures with α-tocopherol (TOH) and/or ascorbyl palmitate (AscPH), were studied during bulk lipid autoxidation at 80 °C. The highest oxidation stability of lipid substrate, in the presence of individual compounds, was found for TOH, followed by D1(OH)2 and M1OH, determined from the main kinetic parameters (antioxidant efficiency, reactivity and capacity). AscPH did not show any protective effect. Synergism was obtained for the binary mixtures of (TOH+AscPH) [42.4%], (M1OH+TOH) [32.4%] and (M1OH+AscPH) [35.6%] and for the ternary mixture of (M1OH+TOH+AscPH) [28.7%]. Different protective effects observed were explained on the basis (of results) of TOH regeneration and its content determined by HPLC. These antioxidant binary and ternary mixtures can be used as functional components of foods with health-promoting effects.