Antiradical Agents Research Articles

Aframomum Melegueta: Evaluation of Chronic Toxicity, HPLC Profiling, and In Vitro/In Vivo Antioxidant Assessment of Seeds Extracts.

Aframomum melegueta, commonly known as grains of paradise, is a medicinal plant celebrated for its rich phytochemical content and therapeutic properties. This study evaluated the antioxidant and cytotoxic potentials of its ethanolic and methanolic extracts, both in vitro and in vivo, while also analyzing their chemical profiles. HPLC analysis identified key compounds, including gallic acid, caffeic acid, caffeine, coumarin, rutin, catechin, ferulic acid, and quercetin. Chronic toxicity assessments confirmed the safety of the extracts, with no adverse effects on animal health, particularly in liver histopathology. Cytotoxicity results indicated reduced splenocyte viability at the highest concentrations. The extracts exhibited significant antioxidant activity in DPPH•, FRP, and phosphomolybdate assays, demonstrating their effectiveness as antiradical agents. In vivo antioxidant results showed a reduction in lipid peroxidation levels in serum and liver, highlighting the extracts' ability to mitigate oxidative stress. Additionally, the extracts provided protection against H2O2-induced erythrocyte hemolysis and modulated NO production in peritoneal macrophages. These findings underscore the therapeutic potential of A. melegueta extracts, suggesting their promise in developing preventive strategies for oxidative stress-related chronic diseases.

Potential antioxidant and antiradical agents from Allium ascalonicum: Superoxide dismutase and density functional theory in silico studies.

Antioxidants are compounds that can inhibit excessive free radical reactions in the body. Excessive free radicals can cause system imbalances in the body which can trigger oxidative stress and cause serious illness. The limitations of antioxidants in the body can be overcome by consuming safe natural additional antioxidants that can be obtained from natural products. Isolating compounds of Allium ascalonicum leaves as antioxidant and antiradical agents in inhibiting excessive free radicals by in vitro and in silico. The extracted compounds were purified by column chromatography. The compounds obtained were then characterized using ultraviolet, infrared, NMR, and mass spectrometry. Determination of antioxidant activity was carried out by in vitro using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the non-enzymatic superoxide dismutase (SOD) methods. The in silico study used the density functional theory (DFT) calculation method with global descriptive parameters (GDP), donor acceptor map (DAM), and frontier molecular orbitals (FMO) analysis. Three compounds have been isolated, of which compound 1 is a new compound. In the DPPH method, compound 1 has more strong antioxidant activity than others, as well as in the non-enzymatic SOD method. Whereas, in the DFT calculation shows that compound 1 has the best reactivity and stability between other compounds and was categorized as the best antiradical. Compound 1 has the highest antioxidant activity compared to the other compounds by in vitro both the DPPH and non-enzymatic SOD methods. In silico, compound 1 has the potential as the best antiradical.

Free radical scavenging behaviour of the plant-beneficial secondary metabolite 2,4-diacetylphloroglucinol derivatives under physiological conditions: A joint experimental and theoretical study

Undoubtedly, natural products (NPs) offer a crucial foundation for crafting novel biologically relevant scaffolds. Among these, 2,4-diacetylphloroglucinol (DAPG) stands out as a polyketide compound produced by Pseudomonads spp, showcasing substantial antimicrobial activity. This study focuses on synthesising derivatives of DAPG and delving into their structural characteristics, tautomerism, and antiradical properties. Through density functional theory (DFT) calculations at the B3LYP/def2-SVP level, we examined the thermodynamic parameters governing the double H+/e−radical trapping processes. These investigations encompassed both gas phase and physiological environments (lipid-like and aqueous solution media). Comparative analyses were conducted with its analogue (2,4-diisobutyrylphloroglucinol, DBPG), its parent compound (phloroglucinol, PG), and a commercial antioxidant standard (2-butylated hydroxyanisole, 2-BHA). This study unveils that DAPG exhibits a preference for double-sequential proton loss electron transfer (dSPLET) as the favoured mechanism within physiological environments. Additionally, we computed redox potentials and equilibrium constants to discuss the effectiveness of the overall scavenging process against diverse reactive oxygen, nitrogen, and sulphur species (ROS, RNS, and RSS). Further insights were gained through molecular docking studies, evaluating the potential inhibition against several ROS-generating enzymes such as xanthine oxidase (XO), lipoxygenase (LO), CYP2C9 (CP450), and NADPH-oxidase (NO). Comprehensive discussions regarding the effects of modifications on PG rings were also conducted. In addition, bioinformatic POM (Petra/Osiris/Molinspiration) analyses were reported to aid in clarifying the experimental data and DFT calculations. Ultimately, this study advocates for the development of potent acyl phloroglucinols (ACPLs)-based antiradical agents, shedding light on how structural characteristics influence their radical scavenging potential.

Assessing the Dual Use of Red and Yellow Algerian Pomegranate Husks: Natural Antiradical Agents and Low-Cost Biosorbents for Chromium (VI) Removal from Contaminated Waters

The hexavalent chromium (Cr(VI)) released in industrial wastewaters can cause adverse effects on both the environment and human health. This study aimed to investigate the efficiency of the red and yellow pomegranate husk powders (RHP and YHP) as natural quenchers for free radicals and as adsorbents towards Cr(VI) ions. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) surface area analyses were used for biosorbent characterization. The antiradical activity was assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. The adsorption isotherms and kinetics were conducted by the batch method. The results showed the roughness and heterogeneity of the biosorbent surface in the presence of active functional groups. At a dose of 5 mg, both biomasses showed a radical inhibition activity (I) > 85% for DPPH, and (I) > 91% for ABTS. Finally, the isotherms modeling showed that the Langmuir model was the best fit with a maximum adsorption capacity (Qmax) of 413.22 and 403.22 mg/g at pH 2 within 60 min with a solid/liquid ratio (S/L) of 0.5 mg/mL for RHP and YHP, respectively. The kinetic data aligned better with the pseudo-second-order model. This study demonstrates the effectiveness of these biomasses as natural quenchers for free radicals and as biosorbents for Cr(VI) removal from contaminated waters.

A green and effective route leading to antiradical agents with 3-arylmethyl 4-hydroxyquinolin-2(1H)-one moiety

A new, green, convenient, cost- and atom effective route leading to 3-arylmethyl 4-hydroxyquinolin-2(1H)-ones from arylaldehydes and 1,3-dicarbonyl compounds in triethyl ammonium formate in good to excellent yield is presented. The provided method foresees the Knoevenagel condensation between a 4-hydroxyquinolin-2(1H)-one and an aromatic aldehyde followed by in situ trapping of the arylidene intermediate with the hydride ion. All synthesized compounds were tested for their antiradical activity against DPPH and GO free radicals. The antiradical activity of the 3-arylmethyl 4-hydroxyquinolin-2(1H)-ones was comparable to or even higher than that of some commercially widely used antioxidants like BHT, TBHQ, or α-tocopherol.

Ceylon cinnamon and clove essential oils as promising free radical scavengers for skin care products

Abstract Due to adverse effects of free radicals on human skin and increasing consumer demand for natural ingredients, essential oils from basil, Ceylon cinnamon bark, clove, juniper, lavender, oregano, rosemary, tea tree, thyme, and ylang-ylang were assessed for their antiradical activity. The oils were evaluated in the concentration range of 5—0.1 mg·mL−1, in which the three reference synthetic antioxidants are most often added to mass-produced cosmetics. Among all examined samples, C. cinnamon oil at a concentration of 5 mg·mL−1 showed the strongest DPPH radical scavenging activity (0.41 mg·mL−1 IC50), followed by clove oil, BHA, α-tocopherol, and BHT (0.82, 0.84, 0.88 and 0.93 mg·mL−1 IC50), respectively. At the same concentration, the reduction power of C. cinnamon oil was higher (1.64 mg·mL−1 Trolox Eq.) than that of α-tocopherol and BHT (1.42 and 0.80 mmol·L−1 Trolox Eq., respectively) but lower than that of BHA (1.81 mmol·L–1 Trolox Eq.). Antiradical activity of the other eight essential oils was low or negligible. C. cinnamon oil and clove oil are promising antiradical agents for skin care but according to our GC-MS analysis, these oils contain 0.29 % of cinnamaldehyde, 0.03 % of linalool, 0.02 % of D-limonene, and 0.02 % of eugenol or 0.41 % of eugenol and 0.002 % of linalool, respectively, which are monitored contact allergens in cosmetics. Such a product is not be suitable for consumers allergic to these substances but for the vast majority of consumers it does not pose a risk in terms of allergic manifestations.

Protective Effect of Dinitrosyl Iron Complexes Bound with Hemoglobin on Oxidative Modification by Peroxynitrite.

Dinitrosyl iron complexes (DNICs) are a physiological form of nitric oxide (•NO) in an organism. They are able not only to deposit and transport •NO, but are also to act as antioxidant and antiradical agents. However, the mechanics of hemoglobin-bound DNICs (Hb-DNICs) protecting Hb against peroxynitrite-caused, mediated oxidative modification have not yet been scrutinized. Through EPR spectroscopy we show that Hb-DNICs are destroyed under the peroxynitrite action in a dose-dependent manner. At the same time, DNICs inhibit the oxidation of tryptophan and tyrosine residues and formation of carbonyl derivatives. They also prevent the formation of covalent crosslinks between Hb subunits and degradation of a heme group. These effects can arise from the oxoferryl heme form being reduced, and they can be connected with the ability of DNICs to directly intercept peroxynitrite and free radicals, which emerge due to its homolysis. These data show that DNICs may ensure protection from myocardial ischemia.

Microwave-assisted synthesis, DFT theoretical study and biological activities evaluation of two phosphonylated m-toluidine derivatives

An easy and efficient microwave-assisted method has been developed for the synthesis of two phosphonylated molecules: α-aminophosphonic acid (MTA) and α-aminophosphonate ester (MTE). To achieve these, we have synthesized the products from m-toluidine, under microwave conditions. All of the obtained compounds were characterized by Microanalysis, UV–Vis, FT-IR, and 1H, 13C and 31P NMR spectroscopic methods. The spectral results are in good line with the proposed structures. Density Functional theory (DFT) calculations were carried out using Gaussian09 program package, using 6–31G++(d,p) basis set. The frontier orbital energies were presented and have been used to predict global reactivity indices. Results showed that MTE is more reactive and less stable than MTA. The Mulliken atomic charges, dipole moment and thermodynamic proprieties were also calculated and discussed. In addition, the target compounds were evaluated for their in vitro antioxidant, antimicrobial and antienzymatic activities. The biological assays indicated that these compounds displayed potent inhibitory activity toward acetylcholinesterase (MTE: 92.71±0.91%, MTA: 67.32±0.52%) and butyrylcholinesterase (MTE: 79.16±0.47% and MTA 34.80±0.76%). It was also found that they act as excellent antiradical agents (ABTS: MTA/226.077±0.29 μg/ml, MTE/ 535,993±0.30 μg/ml and DPPH: MTA/311.853 ± 0.14 μg/ml, MTE/621.627 ± 0.12 μg/ml). In addition, these compounds exhibited the highest antibacterial and antifungal properties.

Spectral, in vitro antiradical and antimicrobial assessment of copper complexes containing tridentate Schiff base derived from dihydroxybenzene functionality with diaminoethylene bridge

The reaction of copper salts with Schiff base ligand: [4-[(1E)-N-{2-[(Z)-(4-methoxybenzylidene)amino]ethyl}ethanimidoyl]benzene-1,3-diol] derived from the condensation of ethylenediamine, 2-hydroxy-1-(4-hydroxyphenyl)ethenone and 4-methoxybenzaldehyde afforded copper complexes bearing chloride, bromide, thiocyanate, nitrate, and acetate. The complexes exhibited crystalline features and excellent thermal stability up to 450 °C. The powder X-ray diffraction pattern suggests a well-defined crystalline structure with average crystallite sizes of < 52 nm. The scavenging ability of 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radicals by the synthesized compounds was studied for their antioxidant potential and screening for antimicrobial activity by p-iodonitrotetrazolium chloride colorimetric assay. The investigated assays suggest that the synthesized compounds are potent antiradical and antimicrobial agents. Research highlights An eco-friendly method was followed for the synthesis of functionalized tridentate ONN Schiff base ligand. Five Schiff base copper(II) complexes were synthesized bearing chloride, bromide, thiocyanate, nitrate, and acetate. Structural features were characterized by CHN, PXRD, TG-DTG, NMR, UV–Vis, and FT-IR spectro-analytical techniques. Schiff base ligand and its copper complexes showed good to excellent DPPH and ABTS radicals scavenging capability. Cu(II) complexes of Schiff base ligand (MEB) showed good antimicrobial properties via the p-iodonitrotetrazolium chloride (INT) colorimetric assay.

Combined experimental and theoretical studies of the structure-antiradical activity relationship of heterocyclic hydrazone compounds

The present paper describes combined experimental and theoretical studies of twelve heterocyclic compounds bearing hydrazone functional group (1–12). Experimentally, the free radical scavenging activity of all the compounds have been investigated using DPPH, ABTS, and DMSO alkaline assays. The obtained results showed that these compounds are potent antiradical agents. The best results have been obtained with the imidazole derivatives 5 and 12, which showed higher antiradical activity than the BHT standard in DPPH and ABTS assays. Theoretical calculations, by means of DFT/B3LYP approach, were carried out in order to explain the experimental results. Some structural characteristics such as molecular descriptors, highest occupied molecular orbital, and molecular electrostatic potential mapping have been computed. The mechanisms, HAT (hydrogen atom transfer), SETPT (sequential electron transfer proton transfer), and SPLET (sequential proton loss electron transfer) have been studied and discussed. In addition, the reactions toward HO•, MeO•, HOO•, and MeOO• radicals have been investigated. As results, the radical scavenger properties of the studied compounds were confirmed. The HAT was found to be the thermodynamically dominant mechanism in the gas-phase for all the studied compounds, whereas the SPLET mechanism is the thermodynamically favorable pathway in ethanol. A good correlation with DPPH and ABTS assays was found between experimental and theoretical results.

Preparation of Retinoyl-Flavonolignan Hybrids and Their Antioxidant Properties

Antioxidants protect the structural and functional components in organisms against oxidative stress. Most antioxidants are of plant origin as the plants are permanently exposed to oxidative stress (UV radiation, photosynthetic reactions). Both carotenoids and flavonoids are prominent antioxidant and anti-radical agents often occurring together in the plant tissues and acting in lipophilic and hydrophilic milieu, respectively. They are complementary in their anti-radical activity. This study describes the synthesis of a series of hybrid ester conjugates of retinoic acid with various flavonolignans, such as silybin, 2,3-dehydrosilybin and isosilybin. Antioxidant/anti-radical activities and bio-physical properties of novel covalent carotenoid-flavonoid hybrids, as well as various mixtures of the respective parent components, were investigated. Retinoyl conjugates with silybin—which is the most important flavonolignan in silymarin complex—(and its pure diastereomers) displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than both the parent compounds and their equimolar mixtures.

Antiradical properties of chemo drug, carboplatin, in cooperation with ZnO nanoparticles under UV irradiation in putative model of cancer cells

The main objective of this study was to assess the antiradical properties of zinc oxide (ZnO) nanoparticles upon exposure to ultraviolet radiation with carboplatin, an anti-proliferative drug used in the treatment of retinoblastoma. For the purpose of this study, the decomposition of 2,2(diphenyl-1-picryhydrazyl) radical (DPPH*) was used to assess the free radical capacity of antioxidants and was followed by MTT measurements. To test the antiradical capacity, the effective concentration, antiradical power, stoichiometry, and number of reduced DPPH* were investigated. DPPH* has a peak absorbance at a wavelength of 515 nm, which disappears upon the introduction of the antiradical agents. Four agents were reacted with DPPH* and represented the possible reaction kinetic categories. ZnO nanoparticles and carboplatin-loaded ZnO nanoparticles reacted more strongly with DPPH* and approached a saturation state at 420 min. The remaining two antiradical agents, ZnO nanoparticles under UV radiation and carboplatin-loaded ZnO nanoparticles under UV radiation, reacted a bit slower with DPPH* and approached a steady state at 1440 min. Among the different four antiradical agents, carboplatin-loaded ZnO nanoparticles under UV light had the highest antiradical response with the lowest effective concentration value to the reduced DPPH* molecules. ZnO nanoparticles alone were found to be poor antiradical agent. Possible mechanisms were attributed to the number of hydroxyl groups available to decrease the number of DPPH*.

Influence of various factors on the antiradical activity of Panax ginseng С. A. Meyer extracts

Aim. The aim of the work was to evaluate the anti-radical activity of extracts of ginseng's underground and overground organs Panax ginseng C.A. Mey, depending on various factors – age of plants, collection time and cultivation conditions. Methods. Extracts obtained from various plant organs were evaluated in the model system with cation-radicals ABTS. At the same time, the amount of extractive substances and phenolic compounds was determined. Results. Samples of leaves and roots of ginseng of 1, 2, 3, 5, 9 years of vegetation from the collection of the Central Botanical Garden of the National Academy of Sciences of Belarus were analyzed. It is established that extracts of ginseng leaves of P. ginseng can be considered as sufficiently effective anti-radical agents. Anti-radical activity of extracts of roots and leaves of ginseng differed significantly depending on the weather conditions of the growing season. Conclusions. It is shown that extracts of ginseng leaves differ by the maximum antiradical activity. Extracts of ginseng roots showed a much lower anti-radical activity in comparison with leaf extracts, which may be due to both a smaller amount of extractives extracted from water-ethanol extraction and their composition.&#x0D; Keywords: ginseng, antiradical activity, phenolic compounds, extractives.

Synthesis and antiradical activity of novel copper(II) complexes of long chain reduced Schiff base ligands

Oxidative stress is the cause of many diseases and at the heart of it is the overproduction of reactive oxygen species (ROS). There are several protective enzymes, e.g., superoxide dismutases (SOD), able to decrease the level of ROS in the cell; however, a therapeutic use of these enzymes is problematic. Small molecule compounds and complexes able to scavenge free radicals such as superoxide anion radicals could be used instead. These compounds are often called SOD-mimics and various researches are interested in synthesis and study of these compounds. In our study, a series of Cu(II) complexes were synthesized, containing reduced Schiff base ligands prepared from salicylaldehyde and amino acids with longer chain length (5-aminopentanoic acid, 6-aminohexanoic acid, 8-aminooctanoic acid, 11-aminoundecanoic acid, and 12-aminododecanoic acid). Complexes prepared from these ligands are novel and were prepared using three different methods. An assay based on the ability to inhibit reduction of iodonitrotetrazolium dye by superoxide anion radicals was used to determine antiradical activity of the prepared complex. Most of the prepared complexes proved to be good antiradical agents compared to cystamine and the copper(II) complex with Schiff base type ligand N-salicylidene-β-alanine. The best IC50 values of the radical transfer of the prepared compounds were two complexes of N-(2-hydroxybenzyl)-11-aminoundecanoic acid: 97.0 ± 1.9 and 45.1 ± 0.5 μM.

Design of chalcogen-containing norepinephrines: efficient GPx mimics and strong cytotoxic agents against HeLa cells.

Numerous chronic diseases exhibit multifactorial etiologies, so focusing on a single therapeutic target is usually an inadequate treatment; instead, multi-target drugs are preferred. Herein, a panel of phenolic thioureas and selenoureas were designed as new prototypes against multifactorial diseases concerning antioxidation and cytotoxicity, as a pro-oxidant environment is usually found in such diseases. Selenoureas were excellent antiradical agents and biomimetic catalysts of glutathione peroxidase for the scavenging of H2O2. They were also potent and selective cytotoxic agents against cancer cells, in particular HeLa (IC50 2.77-6.13 μM), apoptosis being involved. Selenoureas also reduced oxidative stress in HeLa cells (IC50= 3.76 μM). Phenolic selenoureas are promising lead structures for the development of drugs targeting multifactorial diseases like cancer.

Analysis of the Oxidative Stress Status in Nonspecific Vaginitis and Its Role in Vaginal Epithelial Cells Apoptosis.

Nonspecific vaginitis (NSV), also named bacterial vaginosis, is one of the most common genital system diseases in women during their reproductive years. The specific pathogenic mechanism of NSV is not clear yet. Upon the balance alteration, large amount of reactive oxidant species (ROS) is generated and accumulated in the genital tract, and thus resulting in oxidative stress, which has been reported to be an important trigger of mitochondrial pathway cell apoptosis. In this study, the antioxidant secretion level and antioxidant enzyme activity in the vaginal discharge were evaluated to analyze the oxidative status in the vaginal tract of NSV patients. The effect of oxidative stress on the vaginal mucosa epithelial cell apoptosis was then studied. The role of oxidative stress on NSV development was uncovered; thus open new direction for the prevention and treatment of NSV by providing antiradical agents was revealed.

Total Phenolic Content, Anti-Radical property and HPLC profiles of Caralluma diffusa (Wight) N.E. Br.

The relevance of free radical mediated degenerative diseases resulted in the investigation of total phenolic content and antioxidant potential of Caralluma diffusa. Quantification of total phenolics, tannins and flavonoids were done as they are the major antioxidant agents present in the plants. Antioxidant ability was assessed through various biochemical assays like ABTS+, FRAP, metal chelating and phosphomolybdenum reduction. HPLC analysis was done to determine the active constituents. The total phenolic, tannin and flavonoid content were found in moderate amount but could be efficient enough to act as anti radical agents. The plant extracts revealed good antioxidant activity in all the assays. In ABTS radical assay, ethyl acetate extract showed better activity (809.32 µM trolox equi/g extract). The hot water extract expressed maximum activity in FRAP (805.42 mM Fe II/mg extract) and metal chelating assays (36.93 %) compared to other extracts. Methanol extract showed highest ascorbic acid equivalence (88.88 g/100 g extract) in phosphomolybdenum assay. The methanol extract also revealed the presence of gallic acid, catechin, caffeic acid and ferulic acid or its analogues. This study put forward the efficiency of C. diffusa as a natural agent to fight against free radical and diseases associated with it.

ANTI-FREE RADICALS: SOURCE, ROLE AND APPLICATION IN DERMO-COSMETOLOGY

Many environmental factors attack our skin continuously: Sun, wind, pollutants and tobacco which constitute the principle skin aggressors. Free radicals which are highly reactive chemical compounds, induce cellular and tissue injuries, and subsequently lead to aging. These free radicals are normally produced by cellular metabolism. They are represented by: OH°, RCOO°, NO° radicals and singlet oxygen. Free radicals are involved in cutaneous aging. Normally these radicals are neutralised by natural or human antiradical agents like superoxide dismutase, glutathione reductase, glutathione peroxidase and others. Some pathologic situations (cancer, Alzheimer disease, Crohn’s disease, atherosclerosis, diabetes mellitus …) are characterized by an over production of these radicals where the natural defences become overwhelmed. Oral administration of exogenous substances like vitamin A, C, E, oligoelements Cu, Zn, Se, Mn decrease free radical harmful and deleterious effects. Nature has several means to fight against oxidative stress: polyphenols, flavonoides and lipids are antiradical substances of plant origin. The future belongs to understand natural antiradical mechanisms as well as the synthesis of new molecules which would be effective in prevention of harmful effects produced by these radicals.

Antiproliferative effect of antioxidant polyphenols from grape in murine Hepa-1c1c7.

Grapes and wine contain high concentrations of polyphenolic compounds. Although their cancer protective effect has been well documented, their activity as anticarcinogens should be cautiously considered since the molecular bases of action and their applicability to human cancer prevention are still unclear. We studied the antioxidant/antiradical activity and the antiproliferative effect in vitro of different polyphenolic mixtures, extracted from grapes and fractionated through RP-HPLC. The polyphenolic fractions were chemically characterized and their antioxidant/antiradical activity was determined by the DPPH assay. Mouse hepatoma Hepa-1c1c7 cells were used to study the cell growth inhibition capacity of these fractions by MTT assay. Their capacity of altering cell cycle and possible induction of apoptosis was examined using FACS analysis. The original polyphenolic fraction OW, which contained gallic acid (GA), (+)-catechin (Cat), (-)-epicatechin (Ec), glycosylated flavonols (F) and procyanidin oligomers was fractionated into fraction I, composed of monomers and small oligomers, and fraction II that included flavonols and procyanidin oligomers of higher molecular weight. The three polyphenolic fractions tested showed quite similar antiradical activity, although fraction I was the most potent antiradical agent (lowest ED(50) value: 9 microg). Fraction II was the least potent cell growth inhibitor (highest IC(50) value: 100 microg/ml) but showed the strongest effect on the cell cycle of Hepa-1c1c7, inducing apoptosis in those cells. The original fraction OW was demonstrated to have the most potent cell growth inhibition effect (lowest IC(50) value: 43 microg/ml). However, it only appeared to alter cell cycle of Hepa-1c1c7 at concentrations higher than its IC(50) and did not induce apoptosis in those cells. A similar effect on cell cycle and apoptosis was encountered for fraction I. The polyphenolic fractions tested in this study were potent antiradical agents and exerted an antiproliferative effect in mouse hepatoma Hepa-1c1c7 cells; the fraction with the highest degree of polimerization and galloylation (fraction II) had the most influence on the cell cycle and induction of apoptosis on Hepa-1c1c7.