Influence of the composition of essential oils on their antioxidant and antiradical properties

The antiradical and antioxidant properties of essential oil mixtures (EOMs) with various compositions were studied and compared in model systems of hexanal autooxidation, thermal oxidation of methyl linoleate and beta3-carotene, and in a reaction with the stable diphenylpicrylhydrazyl radical. It was found that all EOMs under investigation exhibited antiradical activity. The highest antiradical activity was observed for an EOM containing monoterpene hydrocarbons as the main components (the phenol content was low). The antioxidant activity of all EOMs was from 60 to 98% and depended on the model system composition and the method of assay. The mixture with the highest phenol content exhibits the highest antioxidant activity level in the hexanal autooxidation system. EOMs with a high content of phenols and alpha- and y-terpinenes were the most efficient antioxidants in the beta3-carotene model system. The study confirmed the possibility to vary the antioxidant and antiradical properties of essential oils by preparing their mixtures with a specific composition.     

Influence of the composition of essential oils on their antioxidant and antiradical properties

The antiradical and antioxidant properties of essential oil mixtures (EOMs) with various compositions in model systems of hexanal autooxidation, thermal oxidation of methyl linoleate and β-carotene, and in a reaction with the stable diphenylpicrylhydrazyl radical were studied and compared. It was found that all studied EOMs exhibited antiradical activity. The highest antiradical activity was observed for an EOM containing monoterpene hydrocarbons as the main components (the phenol content was low). The antioxidant activity of all EOMs was from 60 to 98% and depended on the model system composition and the method of assay. The mixture with the maximum phenol content exhibits the highest antioxidant activity level in the hexanal autooxidation system. EOMs with a high content of phenols and α- and γ-terpinenes were the most efficient antioxidants in the β-carotene model system. The study confirmed the possibility to vary the antioxidant and antiradical properties of essential oils by preparing their mixtures with a specific composition.     

Comparison of the antiradical activity of ionol, components of fresh ginger, and its extracts

The antiradical properties of three samples of ginger (Zingiber officinale R.)—juice from fresh rhizome, essential oil, and extracts (oleoresin)—were studied and compared with the properties of synthetic antioxidant ionol (butylatedhydroxy-toluene, BHT). Reaction antioxidants with stable free 2,2-diphenyl-1-picrylhydrozyl radicals were used as model systems. DPPH equivalents per gram of ginger sample, EC₅₀, and antiradical efficiency (AE) were determined. The EC₅₀ and AE values for ginger oleoresin and BHT were similar. They were the same as those of highly active natural antioxidants, and the values for essential oil and ginger juice were lower by two orders of magnitude. On the base of kinetic parameters, the ginger samples may belong to antiradical compounds with prolonged action.     

Cysteinyl-flavan-3-ol conjugates from grape procyanidins. Antioxidant and antiproliferative properties

New bio-based antioxidant compounds have been obtained by depolymerisation of grape polymeric flavanols in the presence of cysteine. Their preparation and purification, as well as their antiradical/antioxidant and antiproliferative properties are reported. 4beta-(S-cysteinyl)epicatechin 5, 4beta-(S-cysteinyl)catechin 6 and 4beta-(S-cysteinyl)epicatechin 3-O-gallate 7 were efficiently purified from the crude depolymerised mixture by cation-exchange chromatography and preparative reversed-phase chromatography. The new compounds were more efficient than the underivatised (-)-epicatechin 1 as scavengers of the 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH) and weak growth inhibitors of human colon carcinoma HT29 cells. The order of antiradical and antiproliferative efficiency was 7 >5 approximately 6 >1, the same for both assays.     

Antiradical protective systems in the plasma membranes of an irradiated animal

In the purified plasma membranes of rat liver the antiradical protection systems were revealed involving superoxide dismutase, glutathione peroxidase, glutathione reductase, lipid-dependent and water-soluble catalase, and reduced glutathione. Early changes were observed in these systems after total-body X-irradiation (LD50/30). The authors discuss the role of a plasma membrane in the radiation response of cells.     

Caffeoylquinic Acids: Separation Method,Antiradical Properties and Cytotoxicity

Twelve chlorogenic acid derivatives and two flavones were isolated from Moquiniastrum floribundum (Asteraceae, other name: Gochnatia floribunda). Compounds were evaluated in relation to their cytotoxicity and antiradical properties. Cytotoxicity was not observed for compounds, however, chlorogenic acid derivatives showed antiradical activity and were more active than the Trolox standard. Quinic acid esterified with caffeoyl group at C‐4 position showed higher antiradical activity compared to acylation at C‐3 or C‐5 positions. Additional caffeoyl groups esterified in quinic acid increase the antiradical activity observed for 4‐caffeoylquinic acid. Excepted to 3,4‐dicaffeoylquinic acid methyl ester, methyl ester derivatives show higher capacity of trapping radicals than their respective acids. Consequently, the presence of caffeoyl group at C‐4 position of quinic acid is suggested as fundamental to obtain the highest antiradical activity.     

Antioxidative and antiradical properties of plant phenolics

The plant phenolic compounds such as flavonoids, tannins and phenolic acids appeared to be strong antiradical and antioxidant compounds. The number of hydroxy groups and the presence of a 2,3-double bond and orthodiphenolic structure enhance antiradical and antioxidative activity of flavonoids. The glycosylation, blocking the 3-OH group in C-ring, lack of a hydroxy group or the presence of only a methoxy group in B-ring have a decreasing effect on antiradical or antioxidative activity of these compounds. Tannins show strong antioxidative properties. Some tannins in red wine or gallate esters were proved to have antioxidative effect in vivo. The number of hydroxy groups connected with the aromatic ring, in ortho or para position relative to each other, enhance antioxidative and antiradical activity of phenolic acids. The substitution of a methoxy group in ortho position to the OH in monophenols seems to favour the antioxidative activity of the former.     

Antiradical properties of oregano, thyme, and savory essential oils

In model reactions with the stable free 2,2-diphenyl-1-picrylhydrazyl radical, the antiradical properties of essential oils of thyme (Thymus vulgare), oregano (Origanum vulgare), and savory (Satureja hortensis) that are similar in the qualitative composition, but differ in the quantitative content of the main components, were studied and compared with the properties of synthetic antioxidant ionol. The reaction rates of components of essential oils with the radical were almost identical for all essential oils and were twice the reaction rate of ionol. The antiradical efficiency values were close to each other for all essential oils and by an order of magnitude smaller than for ionol.     

The mechanisms of the antioxidant action of shielded phenols in biological membranes. The effects of 4-methyl-2,6-di-tert-butylphenol (ionol) and its derivatives

According to Bulgarian-Soviet program "Biostab" we studied characteristics of different phenol compounds (ionol derivatives). The aim of the present study is to determine antiradical and antioxidant activity of a number of ionol derivatives in pure chemical systems and in different membrane fractions of a natural origin.     

Antiradical and antioxidant activities of alkaloids isolated from Mahonia aquifolium. Structural aspects

The antioxidant activities of three alkaloids isolated from Mahonia aquifolium--berberine, jatrorrhizine, and magnoflorine--were studied with respect to their structural aspects, particularly the presence and the position of -OH groups, steric conditions of unpaired electron delocalization and parameters of lipophilicity and hydration energy. The antiradical activities of the compounds tested were evaluated as the reactivities toward free stable alpha,alpha'-diphenyl-beta-picrylhydrazyl radical (DPPH). The antioxidant features of the alkaloids tested were investigated in heterogeneous membrane system of DOPC liposomes stressed by peroxidative damage induced by AAPH azoinitiator. Both alkaloids bearing free phenolic groups--jatrorrhizine and magnoflorine--showed better activities in both systems used than berberine not bearing any readily abstractable hydrogen on its skeleton. The former two showed antiperoxidative efficiency in DOPC liposomal membrane comparable to that of an effective scavenger of peroxyl radicals--stobadine-and higher than that of Trolox. We conclude that the favorable antioxidant features of the hydroxylated alkaloids are most probably ensured by the combination of reasonably high antiradical reactivity with high lipophilicity, however, the solvation process was found to markedly interfere with these beneficial effects.     

Novel multi-functional nitrones for treatment of ischemic stroke

Ischemic stroke resulting from obstruction of blood vessels is an enormous public health problem with urgent need for effective therapy. The co-administration of thrombolytic/antiplatelet agent and neuroprotective agent improves therapeutic efficacy and agent possessing both thrombolytic/antiplatelet and antiradical activities provides a promising strategy for the treatment of ischemic stroke. We have previously reported a novel compound, namely TBN, possessing both antiplatelet and antiradical activities, showed significant neuroprotective effect in a rat stroke model. We herein report synthesis of a series of new pyrazine derivatives, and evaluation of their biological activities. Their mechanisms of action were also investigated. Among these new derivatives, compound 21, armed with two nitrone moieties, showed the greatest neuroprotective effects in vitro and in vivo. Compound 21 significantly inhibited ADP-induced platelet aggregation. In a cell free antiradical assay, compound 21 was the most effective agent in scavenging the three most damaging radicals, namely (·)OH, O(2)(·-) and ONOO(-).     

Unsolved problems of human cell defence against radiation

The complex of human cell defence systems against gamma-radiation was investigated: DNA repair, antiradical system, GST-family M1 and T1, radioadaptive response. Were compared in repair-deficient cells the action of natural (carlic extract) and synthetic (crown-compound) antimutagens. New approach related to the detection of the activity of different defence systems is developing. It helps to estimate the individual sensitivity to mutagens.     

Chemical composition and biological action of rowanberry extract

The object of this study was the extract from the dried pomace of the Amur rowanberry (Sorbus amurensis Koehne) after the juice separation. The content of total polyphenols, lipid composition, and antiradical activity of the extract were studied. The total content of polyphenols proved to be 80 ± 2,5 mg-equivalents of gallic acid per 100 mL of the extract, suggesting the high level of its antiradical activity (29.73 ± 0.23 mmolequivalents of trolox per liter). The lipid part of the extract included three phospholipid fractions and six fractions of neutral lipids. Their content was found to be 13.4 ± 0.14 mg of total lipids/mL. These results pointed to a high biological activity of the extract which could be considered as a promising object for further experimental studies. The Amur rowanberry extract was shown to exhibit a pronounced antioxidant and hepatoprotective activity on the laboratory model of the carbon-tetrachloride-induced hepatitis in rats with endogastric administration at a dose of 100 mg of total polyphenols per kg of body weight. Administration of the extract resulted in a decrease in the content of total lipids, specific liver weight, and the activity of alanine aminotransferase. The level of the reduced glutathione and the activity of antioxidant and lysosomal enzymes were also normalized. The rowanberry extract seemed to be a promising source for the creation of biologically active food supplements with high antioxidant and antiradical activity.     

Antioxidant and antiproliferative activity of curcumin semicarbazone

A new semicarbazone derivative of curcumin (CRSC) was synthesized and examined for its antioxidant, antiproliferative, and antiradical activity and compared with those of curcumin (CR). The antioxidant activity was tested by their ability to inhibit radiation induced lipid peroxidation in rat liver microsomes. The antiproliferative activity was tested by studying the in vitro activity of CRSC against estrogen dependant breast cancer cell line MCF-7. Kinetics of reaction of (2,2'-diphenyl-1-picrylhydrazide) DPPH, a stable hydrogen abstracting free radical was studied to measure the antiradical activity using stopped-flow spectrophotometer. Finally one-electron oxidized radicals of CRSC were generated and characterized by pulse radiolysis. The results suggest that the probable site of attack for CRSC is both the phenolic OH and the imine carbonyl position. CRSC shows efficient antioxidant and antiproliferative activity although its antiradical activity is less than that of CR.     

Evaluation of antiradical properties of components of the ginger root

Antiradical properties of components of juice of the fresh ginger root and essence and oleoresin of ginger (Zingiber officinale R.) were studied and compared with the properties of the ionol synthetic antioxidant. A reaction with the stable free 2,2-diphenyl-1-picrylhydrazyl radical was used for the evaluation of the antiradical properties. Rates of the fast phase of this reaction and equivalent concentrations of the antiradical components in the ginger samples were determined from kinetic curves of this reaction phase. The values of EC50 and antiradical efficacy (AE) found for the ginger oleoresin were close to those of ionol and characteristic of highly active natural antioxidants, whereas the same values for the ginger essence and juice were two orders of magnitude lower. The ginger preparations belonged to the antiradical compounds of prolonged action according to their kinetic parameters.     

Antioxidant and antiradical activities of resorcinarene tetranitroxides

Resorcinarene oxazines bearing four TEMPO fragments at the wide rim of the macrocycle were prepared through the aminomethylation of resorcinarene octols with 4-amino-TEMPO and formaldehyde. Tetra-TEMPO resorcinarenes are efficient scavengers of 1,1-diphenyl-2-picrylhydrazyl radicals. The model studies revealed that macrocyclic structure and intramolecular hydrogen bonding make considerable contribution to antiradical activity of these compounds. Tetra-TEMPO resorcinarenes show also superoxide dismutase-like activity and efficiently inhibit ABAP-induced peroxidation of linoleic acid.     

Antiradical and NO-inhibiting activities of bet-hydroxy(ethoxy) derivatives of nitrous heterocycles

The antiradical and NO-inhibiting activities of beta-hydroxy(ethoxy) derivatives of nitrous heterocycles (3-hydroxypyridine, 5-hydroxybenzimodazole, and 6-hydroxy(alkoxy)-benzothiazole) have been studied. The antiradical activity has been studied using a homogeneous hydrophilic chemiluminescent system, and the quenching constants (Ki) have been determined. For the most reactive compound, 4-methylthiobenzimidazolyl-3-hydroxypyridine, Ki = 4.5 x 105 M(-1). The NO-inhibiting activity was estimated on a model of the endotoxin shock of experimental animals using a spin trap of nitric oxide radicals based on complexes of iron with sodium diethyldithiocarbamate. It was found that the compounds at doses of 0.25-1 mmol/kg have both the inhibitory and stimulating action on the production of nitric oxide in the liver of animals. The results obtained suggest that some derivatives of nitrous heterocycles can be used as effective antioxidant preparations.     

Biosynthesis and radical scavenging activity of betalains during the cultivation of red beet (Beta vulgaris) hairy root cultures

Betalains biosynthesis and antiradical scavenging activity were investigated during cultivation of four hairy root cultures of Beta vulgaris, obtained from different cultivars (Bordo, Egyptian, Detroit 2 and Detroit Dark Red). The best producer of betalains was a hairy root culture from Beta vulgaris cv. Detroit Dark Red (13.27 mg/g dry weight total pigment production). The ethanol extract, derived from roots of the same culture grown for 15 days under submerged conditions, showed a high antiradical activity (83% of inhibition of the stable DPPH.).     

Stable free radical scavenging and antiperoxidative properties of resveratrol compared in vitro with some other bioflavonoids

Stable free radical scavenging and antiperoxidative activities of resveratrol, a component of grapes and red wine, were evaluated and compared with some other known bioflavonoids (quercetin, catechin, kaempferol, myricetin, fisetin, ellagic acid and naringenin) widely present in the plant kingdom. Free radical scavenging activity was measured in an in vitro chemical system (DPPH assay), while for antiperoxidative activity, biological system comprising of hepatic and pulmonary homogenates was employed. Antiradical activity assay showed quercetin and myricetin to be stronger antiradical agents than resveratrol. Structure-activity study revealed that O-dihydroxy group on ring B of flavonoid plays a crucial role. A double bond at 2-3 position conjugated with a 4-oxo function and hydroxy groups at positions 3 and 5 also contribute towards antiradical activity of flavonoids. Resveratrol exhibited stronger antiradical activity than kaempferol and naringenin and was also more efficient than alpha-tocopherol, a known strong endogenous non-flavonoid antioxidant, used for comparison. In vitro antiperoxidative assay showed fisetin as the strongest and kaempferol as the weakest antioxidant. Resveratrol was found to be stronger antioxidant than catechin, myricetin, kaempferol and naringenin, but was weaker than quercetin, fisetin and alpha-tocopherol. Antiradical and antiperoxidative activities of resveratrol may explain its beneficial effects in disease states. Assays exhibited no direct correlation between antiradical and antiperoxidative activities of the phenolics.     

Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors

Potent and selective TACE and MMP inhibitors utilizing the diazepine and thiazepine ring systems were synthesized and evaluated for biological activity in in vitro and in vivo models of TNF-alpha release. Oral activity in the mouse LPS model of TNF-alpha release was seen. Efficacy in the mouse collagen induced arthritis model was achieved with diazepine 20.