Structure-antioxidant activity relationships of flavonoids: a re-examination

The antioxidant and prooxidant activities of flavonoids belonging to several classes were studied to establish their structure-activity relationships against different oxidants. Special attention was paid to the flavonoids quercetin (flavone), taxifolin (flavanone) and catechin (flavanol), which possess different basic structures but the same hydroxylation pattern (3,5,7,3',4'-OH). It was found that these three flavonoids exhibited comparable antioxidant activities against different oxidants leading to the conclusion that the presence of ortho -catechol group (3',4'-OH) in the B-ring is determinant for a high antioxidant capacity. The flavone kaempferol (3,5,7,4'-OH), however, in spite of bearing no catechol group, also presents a high antioxidant activity against some oxidants. This fact can be attributed to the presence of both 2,3-double bond and the 3-hydroxyl group, meaning that the basic structure of flavonoids becomes important when the antioxidant activity of B-ring is small.     

Structure-antioxidant and anti-tumor activity of Teucrium polium phytochemicals

Chemical characterization as well as antioxidant and anti-tumor activity are reported for isolated metabolites from Teucrium polium L. (Lamiaceae). Structures were identified using standard MS and NMR spectroscopic methods. Sesquiterpene absolute stereochemistry was determined based on a modified Mosher’s reaction. Biological activity was evaluated by a cupric reducing antioxidant capacity (CUPRAC) assay and select compounds screened for anti-tumor activity. (1R,4S,10R) 10,11-dimethyl-dicyclohex-5(6)-en-1,4-diol-7-one and (R)-mandelonitrile-β-laminaribioside, together with ten previously reported compounds were identified. Antioxidant versus tumor-inhibition relationships was examined.     

Synthesis and radical-scavenging activity of a dimethyl catechin analogue

Catechin analogue 1 with methyl substituents ortho to the catechol hydroxyl groups was synthesized to improve the antioxidant ability of (+)-catechin. The synthetic scheme involved a solid acid catalyzed Friedel–Crafts coupling of a cinnamyl alcohol derivative to 3,5-dibenzyloxyphenol followed by hydroxylation and then cyclization through an intermediate orthoester. The antioxidative radical scavenging activity of 1 against galvinoxyl radical, an oxyl radical, was found to be 28-fold more potent than (+)-catechin.     

Identification and biological evaluation of flavonoids from the fruits of Prunus mume

This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4′-trihydroxyflavan-(4α → 8)-epicatechin (1), was isolated along with five known flavonoids (2–6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1–6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1–10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.     

Oxidized low density lipoprotein inhibits the hemolytic activity of Asp-hemolysin from Aspergillus fumigatus

We have examined the effect of chemically modified human low density lipoproteins (LDLs) , acetylated LDL and oxidized LDL, on the hemolytic activity of Asp-hemolysin. Oxidized LDL, but not acetylated LDL, inhibited the hemolytic activity of this toxin. The inhibitory effects of oxidized LDL increased with the time of Cu²⁺-induced LDL oxidation. Similar inhibition was observed in the filtrate which was separated from the incubation mixture of Asp-hemolysin with oxidized LDL (for 2 h of oxidation) following ultrafiltration through a membrane with a molecular mass cutoff of 100 000. However, at longer LDL oxidation times, the inhibition by the filtrates was less than the control mixture without ultrafiltration. We suggest that the inhibition by oxidized LDL was due to the binding of oxidized LDL to Asp-hemolysin at shorter LDL oxidation times .     

The use of classification methods for modeling the antioxidant activity of flavonoid compounds

A study using two classification methods (SDA and SIMCA) was carried out in this work with the aim of investigating the relationship between the structure of flavonoid compounds and their free-radical-scavenging ability. In this work, we report the use of chemometric methods (SDA and SIMCA) able to select the most relevant variables (steric, electronic, and topological) responsible for this ability. The results obtained with the SDA and SIMCA methods agree perfectly with our previous model, in which we used other chemometric methods (PCA, HCA and KNN) and are also corroborated with experimental results from the literature. This is a strong indication of how reliable the selection of variables is. Three-dimensional projection of the hyperboxes for Classes 1 (right) and 2 (left)     

Structure-activity relationships of flavonoids for vascular relaxation in porcine coronary artery

Flavonoids are polyphenolic compounds that are widespread in the plant kingdom, and structure-activity relationships (SAR) for vascular relaxation effects were examined for 17 of them using porcine coronary arteries. Density functional theory was employed to calculate the chemical parameters of these compounds. The order of potency for vascular relaxation was as follows: flavones (apigenin and luteolin) >or= flavonols (kaempferol and quercetin)>isoflavones (genistein and daidzein)>flavanon(ol)es (naringenin)>chalcones (phloretin)>anthocyanidins (pelargonidin)>flavan(ol)es ((+)-catechin and (-)-epicatechin). SAR analysis revealed that for good relaxation activity, the 5-OH, 7-OH, 4'-OH, C2=C3 and C4=O functionalities were essential. Comparison of rutin with quercetin, genistin with genistein, and puerarin with daidzein demonstrated that the presence of a glycosylation group greatly reduced relaxation effect. Total energy and molecular volume were also predictive of their relaxation activities. Our findings indicated that the most effective relaxing agents are apigenin, luteolin, kaempferol and genistein. These flavonoids possess the key chemical structures demonstrated in our SAR analysis.     

Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer

Cancer prevention and treatment using traditional Chinese medicines have attracted increasing interest. This study characterizes antioxidant activity and phenolic compounds of traditional Chinese medicinal plants associated with anticancer, comprising 112 species from 50 plant families. The improved ABTS(*+) method was used to systematically assess the total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC) of the medicinal extracts. The TEAC values and total phenolic content for methanolic extracts of herbs ranged from 46.7 to 17,323 micromol Trolox equivalent/100 g dry weight (DW), and from 0.22 to 50.3 g of gallic acid equivalent/100 g DW, respectively. A positive, significant linear relationship between antioxidant activity and total phenolic content (all R(2) values>/=0.95) showed that phenolic compounds were the dominant antioxidant components in the tested medicinal herbs. Major types of phenolic compounds from most of the tested herbs were preliminarily identified and analyzed, and mainly included phenolic acids, flavonoids, tannins, coumarins, lignans, quinones, stilbenes, and curcuminoids. These medicinal herbs exhibited far stronger antioxidant activity and contained significantly higher levels of phenolics than common vegetables and fruits. Traditional Chinese medicinal plants associated with anticancer might be potential sources of potent natural antioxidants and beneficial chemopreventive agents.     

Structure-activity relationships in a series of melatonin analogues with the low-density lipoprotein oxidation model

Despite an increasing number of publications concerning the antioxidant activity of melatonin, little is known about the structural features responsible for this kind of activity. To understand the role played by the different elements of melatonin structure in its antioxidant activity, we have designed and tested several compounds related to this molecule in the low-density lipoprotein peroxidation model. We present here the results of this study in terms of structure-activity relationships focusing on the influence of the acetamidoethyl side chain, the methoxy group, and the indole heterocycle. In this model, we found that changing the acyl residue generally resulted in more active products. We obtained particularly good results with the nonanoyl derivative which showed a level of activity comparable to that of phenols despite lacking a phenolic function. The presence of a methoxy group in position 5 generally had a beneficial influence on the activity, but when located in position 6, the effects were various. The substitution of a hydroxy for the methoxy group led to phenolic compounds endowed with very high antioxidant activity. Replacing the amide with a ketone function did not affect the activity while replacement with an amine group in some cases resulted in prooxidant compounds. Finally, we compared the efficacy of different aromatic rings. The indole heterocycle proved to be better than benzofurane and naphthalene rings.     

Prenylation enhances the biological activity of dietary flavonoids by altering their bioavailability

Flavonoids are distributed across the plant kingdom and have attracted substantial attention owing to their potential benefits for human health. Several studies have demonstrated that flavonoids prenylation enhances various biological activities, suggesting an attractive tool for developing functional foods. This review provides an overview of the current knowledge on how prenylation influences the biological activity and bioavailability of flavonoids. The enhancement effect of prenylation on the biological activities of dietary flavonoids in mammals was demonstrated by comparing the effect of 8-prenyl naringenin (8PN) with that of parent naringenin in the prevention of disuse muscle atrophy in mice. This enhancement results from higher muscular accumulation of 8PN than naringenin. As to bioavailability, despite the lower absorption of 8-prenyl quercetin (8PQ) compared with quercetin, higher 8PQ accumulation was found in the liver and kidney. These data imply that prenylation interferes with the elimination of flavonoids from tissues.     

Synthesis,antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids

Two 2-amino-1,3,4-thiadiazoles containing phenolic hydroxyl groups were combined with different carboxylic acid chlorides giving sixteen amide derivatives with good antioxidant and antiproliferative potential. The compound 3′c with an adamantane ring displayed excellent DPPH radical scavenging activity and good cytotoxic activity against human acute promyelocytic leukemia HL-60 cells, while 1,3,4-thiadiazole 3′h with 4-chlorophenyl moiety was found to be the most effective in inhibition of survival of lung carcinoma A549 cells. All examined thiadiazoles except 3a and 3′a exerted higher cytotoxic activities on A549 and HL-60 cancer cells when compared with normal fibroblasts MRC-5, pointing to selectivity in their antiproliferative action. Some of the most active novel compounds 3c, 3′c, 3′g and 3′h induced significant increase in the percentage of HL-60 cells in the subG1 cell cycle phase in comparison with the control cells. The induction of cell death in HL-60 cells by these compounds was at least partially dependent on activation of caspase-3 and caspase-8. The compounds 3c and 3′c exerted strong antiangiogenic activity. Furthermore, compounds 3c, 3′c, 3′g and 3′h showed the ability to down-regulate the MMP2 and VEGFA expression levels in the treated HL-60 cells when compared with the control cell samples.     

Effects of catechin and epicatechin on superoxide dismutase and glutathione peroxidase activity,in vivo

Abstract

Objectives

The objective of this study was to investigate the effects of catechin and epicatechin on the activity of the endogenous antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) (as well as the total antioxidant capacity (TAC)) of rats after intra-peritoneal (i.p.) administration.

Methods

Twenty-four Wistar rats were randomly divided into two groups: the experimental group which was administered daily with a 1:1 mixture of epicatechin and catechin at a concentration of 23 mg/kg body weight for 10 days and the control group which was injected daily with an equal amount of saline. Blood and urine samples were collected before and after the administration period, as well as 10 days after (follow-up).

Results

Intra-peritoneal administration of catechins led to a potent decrease in GPx levels and a significant increase in SOD levels. TAC was significantly increased in plasma and urine. Malonaldehyde levels in urine remained stable. In the animals treated with catechins, SOD activity showed a moderate negative correlation with GPx activity.

Discussion

Boosting the activity of the antioxidant enzymes could be a potential adjuvant approach for the treatment of the oxidative stress-related diseases.     

Antioxidant flavonoids from leaves of Polygonum hydropiper L

Ten flavonoid compounds were isolated from the dried leaves of Polygonum hydropiper L. (Laksa leaves), and identified as 3-O-alpha-L-rhamnopyranosyloxy-3',4',5,7-tetrahydroxyflavone; 3-O-beta-D-glucopyranosyloxy-4',5,7-trihydroxyflavone; 6-hydroxyapigenin; 6"-O-(3,4,5-trihydroxybenzoyl) 3-O-beta-D-glucopyranosyloxy-3', 4', 5, 7-tetrahydroxyflavone; scutillarein; 6-hydroxyluteolin; 3',4',5,6,7-pentahydroxyflavone; 6-hydroxyluteolin-7-O-beta-D-glucopyranoside; quercetin 3-O-beta-D-glucuronide; 2"-O-(3,4,5-trihydroxybenzoyl) quercitrin; quercetin. Evaluation of the antioxidative activity, conducted in vitro, by using electron spin resonance (ESR) and ultraviolet visible (UV-vis) spectrophotometric assays, showed that these isolated flavonoids possess strong antioxidative capabilities. Measurement of the Trolox equivalent antioxidant capacity (TEAC) values, against ABTS (2,2'-azinobis(3-ethyl-benzo-thiazoline-6-sulphonic acid) radicals and phenyl-tert-butyl nitrone (PBN) azo initiator (AI) also showed strong anti-oxidative activity. The most powerful of the antioxidants was 2"-O-(3,4,5-trihydroxybenzoyl) quercitrin (galloyl quercitrin). A combination of two flavonoid compounds was tested for synergistic anti-oxidative capacity, but no significant improvement was observed.     

Oxidation of flavonoids by hypochlorous acid: reaction kinetics and antioxidant activity studies

Flavonoids, plant polyphenols, ubiquitous components of human diet, are excellent antioxidants. Hypochlorous acid (HOCl), produced by activated neutrophils, is highly reactive chlorinating and oxidizing species. It has been reported earlier that flavonoids are chlorinated by HOCl. Here we show that flavonoids from flavonol subclass are also oxidized by HOCl, but only if the latter is in a large molar excess (≥?10). The kinetics of this reaction was studied by stopped-flow spectrophotometry, at different pH. We found that flavonols were oxidized by HOCl with the rate constants of the order of 10⁴–10⁵ M^?1 s^?1 at pH 7.5. Antioxidant activity of HOCl-modified flavonoids was measured by 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method. Slightly higher antioxidant activity, compared to parent compounds, was observed for flavonols after their reaction with equimolar or moderate excess of HOCl whereas flavonols treated with high molar excess of HOCl exhibited decrease in antioxidant activity. The mechanism of flavonoid reaction with HOCl at physiological pH is proposed, and biological consequences of this reaction are discussed.     

South African Lippia herbal infusions: Total phenolic content,antioxidant and antibacterial activities

Lippia javanica and Lippia scaberrima are used as herbal remedies and are commercially traded as health teas in southern Africa under the brands “Mosukujane” and “Musukudu”, respectively. This study evaluates the relationship between the presence of phenolic compounds and the antioxidant activities of infusions prepared from four Lippia species (L. javanica, L. scaberrima, L. rehmannii and L. wilmsii) indigenous to South Africa. The antioxidant activities of the infusions, determined by the 2,2-diphenylpycrylhydrazyl (DPPH) method, were also compared to those of popular black, green and herbal tea brands. Of the four indigenous species, infusions of L. javanica and L. wilmsii exhibited the highest antioxidant activities (EC₅₀: 358 and 525 µg/ml, respectively) and contained the most phenolic compounds (14.8 and 14.5 mg/ml of dry weight gallic acid equivalent, respectively). Antibacterial activities of methanolic extracts of the four Lippia species were determined against four human pathogens (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa). The extract of L. javanica was the most active against all the pathogens tested. Those Lippia species (L. javanica and L. wilmsii) previously reported to produce higher levels of the pharmacologically active phenylethanoid glycosides verbascoside and isoverbascoside, portrayed stronger antioxidant and antibacterial activities. This study gives credence to the use of infusions of these Lippia species for their general health benefits.     

酚酸类物质对苜蓿种子萌发及抗氧化物酶活性的影响

实验选用紫花苜蓿体内的4种化感物质包括阿魏酸、香豆素、香草酸、香豆酸,以10-3、10-4、10-5mol·L-1和10-6mol·L-1四个浓度,采用培养皿试纸法和沙培法进行苜蓿种子萌发及幼苗生长试验,研究了苜蓿种子萌发和幼苗生长以及抗氧化保护性酶活性的变化,并就生物量、种子萌发和酶活性等三大指标的敏感性进行了讨论。结果表明,4种化感物质对苜蓿种子萌发及幼苗生长有明显的影响作用,这种影响效应与化感物质的种类及浓度显著相关。其中,10-3mol·L-1的4种化感物质均表现出对苜蓿种子萌发有显著的抑制作用,阿魏酸、香豆素和香草酸达到了极显著的抑制效果。当浓度为10-3mol·L-1时,除香豆酸外,其它3种化感物质均表现出对幼苗体内超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)和抗坏血酸酶(APX)活性有显著的抑制作用,同时使幼苗体内丙二醛(MDA)的含量显著增加;随着浓度的降低,化感物质抑制作用减弱;当浓度降低为10-6mol·L-1时,阿魏酸、香豆素、香草酸则表现出了对上述各种酶活性的轻微促进作用。阿魏酸表现出的化感效应最强,香豆素、香草酸次之,香豆酸最弱。发芽指标受化感物质的影响最敏感、其次是生物量指标,而酶活性指标相对较弱。     

Variation in phenolic compounds and antioxidant activity in apple seeds of seven cultivars

Polyphenols are the predominant ingredients in apple seeds. However, few data are available on the phenolic profile or antioxidant activity in apple seeds in previous researches. In this study, low-molecular-weight phenolic compounds and antioxidant activity in seeds, peels, and flesh of seven apple cultivars grown in northwest China were measured and analyzed using HPLC and FRAP, DPPH, ABTS assays, respectively. HPLC analysis revealed phloridzin as the dominant phenolic compound in the seeds with its contents being 240.45–864.42 mg/100 gDW. Total phenolic content (TPC) measured by the Folin–Ciocalteu assay in apple seed extracts of seven cultivars ranged from 5.74 (Golden Delicious) to 17.44 (Honeycrisp) mgGAE/gDW. Apple seeds showed higher antioxidant activity than peels or flesh; antioxidant activity in seeds varied from 57.59 to 397.70 μM Trolox equivalents (TE)/g FW for FRAP, from 37.56 to 64.31 μM TE/g FW for DPPH, and from 220.52 to 708.02 μM TE/g FW for ABTS. TPC in apple seeds was significantly correlated with all three assays. Principal component analysis (PCA) indicated that Honeycrisp was characterized with high contents of total polyphenols and phloridzin. Our findings suggest that phenolic extracts from apple seeds have good commercial potential as a promising antioxidant for use in food or cosmetics.     

Antioxidant actions of flavonoids: Thermodynamic and kinetic analysis

The benefits of flavonoids on human health are very often ascribed to their potential ability to act diminishing free radical steady state concentration in biological systems providing antioxidant protection. This is an assumption based on the chemical structures of flavonoids that support their capacity to scavenge free radicals and chelate redox-active metals. In this paper we will use thermodynamic and kinetic approaches to analyze the interactions of flavonoids with biological material and from there, extrapolate the physiological relevance of their antioxidant actions. Thermodynamic analysis predicts that both, scavenging of oxygen-derived radicals and the sequestration of redox-active metals are energetically favored. Nevertheless, the actual concentrations reached by flavonoids in most animal and human tissues following dietary ingestion are incompatible with the kinetic requirements necessary to reach reaction rates of physiological relevance. This incompatibility becomes evident when compared to other antioxidant compounds, e.g. α-tocopherol (vitamin E), ascorbate (vitamin C), and glutathione. Alternatively, lipid-flavonoid and protein-flavonoid interactions can indirectly mediate a decrease in oxidant (free radical) production and/or oxidative damage to both cell and extracellular components. The final mechanisms mediating the antioxidant actions of flavonoid will be determined by their actual concentration in the tissue under consideration.     

油菜花粉总黄酮的微波辅助提取及其抗氧化活性研究

采用微波辅助提取法提取油菜花粉总黄酮,通过单因素和正交试验,得到最佳提取条件：80％的乙醇、1：20的料液比、提取时间140s、微波功率242W、提取3次,总黄酮质量分数为（2．64±0．05）％。同时还研究提取物对羟自由基、DPPH自由基的清除作用,以及对小鼠肝组织脂质过氧化的抑制作用,自由基半清除质量浓度和脂质过氧化丰抑制盾奄浓度分剐为0．115、0．325和0．065mg／mL。