Antigenotoxic Activity Research Articles

Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

Aim. Oxidative stress is a consequence of the increased production of free radicals that is caused by the disturbance in the balance of oxidation-reduction activity. Salvianolic acid B is a polyphenol compound, derived from the plant Salvia miltiorrhiza Bunge, which showed significant antioxidant properties. The aim of this study is the investigation of genotoxic potential of salvianolic acid B and evaluation of its antigenotoxic activity against the DNA damage induced by hydrogen peroxide in peripheral blood leukocytes in vitro, using the alkaline Comet assay. Materials and Methods. The evaluation of the ability of various concentrations of salvianolic acid B (12.5μM, 25μM and 50 μM) to reduce the number of cells with DNA damage caused by hydrogen peroxide as an oxidant was performed under two experimental protocols: pretreatment and cotreatment, in order to determine antigenotoxicity on preventive and intervention levels. Results. Results indicate that the salvianolic acid B did not exhibit a genotoxic effect after 30 minutes of incubation, in the tested concentrations. In the pretreatment, a concentration of 50 μM showed a significant decrease of the hydrogen peroxide induced DNA damage. Salvianolic acid B was more effective in reducing DNA damage in cotreatment, where concentrations of 25 μM and 50 μM demonstrated a significant abrogation of DNA damage. Protective effect of salvianolic acid B was dependent on the concentration. Conclusions. The results showed that salvianolic acid B has pronounced antigenotoxic effect on the intervention level, which makes it a potential agent in treatment of diseases in which oxidative DNA damage plays an important role.

Use of Theobroma cacao Pod Husk-Derived Biofertilizer is Safe as it Poses neither Ecological nor Human Health Risks

Cacao farmers use macerated Theobroma cacao pod husks as biofertilizer for restoration of environmentally important soil elements, i.e., N, P, K, Na, Mg, and Ca. The increasing popularity of this organic material for soil management justifies to experimentally ascertaining that its application does not produce environmental or human health risks. We therefore applied a battery of biological tests to assess possible health risks related to the extract of fermented cacao pod husks [CHE]. Minimal inhibitory concentration for selected bacteria and fungi was established and an antiviral assay (equine herpes virus – EHV-1) and insecticide assay (Aedes aegypti larvae), to observe possible environmental impact. Toxicity tests used Artemia salina, hemolytic activity and cytotoxicity were tested using HT-29 e Vero cells, respectively. Genotoxicity and anti-genotoxic activity was tested in the comet assay of leukocytes and a selection of Saccharomyces cerevisiae mutants allowed look for a possible interference of CHE with defined metabolic pathways. None of these established tests used to define toxicity and genotoxicity of chemical compounds indicated that CHE contained substances that would pose such risks. Our safety assessment on bacteria and yeasts, virus, insect larvae, and human leukocytes [3-(4,5-di-methylazol-2- yl)-2,5- diphenyltetrazolium bromide (MTT) and comet assay] thus indicated that macerated cocoa pod husk can be safely used as biofertilizer.

Prevention of DNA damage and anticarcinogenic activity of Activia® in a preclinical model.

Colorectal cancer is a global public health issue. Studies have pointed to the protective effect of probiotics on colorectal carcinogenesis. Activia® is a lacto probiotic product that is widely consumed all over the world and its beneficial properties are related, mainly, to the lineage of traditional yoghurt bacteria combined with a specific bacillus, DanRegularis, which gives the product a proven capacity to intestinal regulation in humans. The aim of this study was to evaluate the antigenotoxic, antimutagenic, and anticarcinogenic proprieties of the Activia product, in response to damage caused by 1,2-dimethylhydrazine (DMH) in Swiss mice. Activia does not have shown antigenotoxic activity. However, the percent of DNA damage reduction, evaluated by the antimutagenicity assay, ranged from 69.23 to 96.15% indicating effective chemopreventive action. Activia reduced up to 79.82% the induction of aberrant crypt foci by DMH. Facing the results, it is inferred that Activia facilitates the weight loss, prevents DNA damage and pre-cancerous lesions in the intestinal mucosa.

Chemopreventive Potential of Powdered Red Wine Pomace Seasonings against Colorectal Cancer in HT-29 Cells.

This study evaluates the antiproliferative and antigenotoxic actions of powdered red wine pomace seasonings (Sk-S, seedless; W-S, whole; Sd-S, seeds). In vitro gastrointestinal digested and colonic fermented fractions of the seasonings were used as cell treatments. Phenolic acids from Sk-S showed the highest bioaccessibility in the small intestine, whereas polyphenols contained in Sd-S might be the most fermentable in the colon. Dietary fiber from Sk-S was the best substrate for short chain fatty acids production by gut microbiota. Colon cancerous (HT-29) cell viability was inhibited by 50% (IC50 values) at treatment concentrations ranging from 845 (Sk-S) to 1085 (Sd-S) μg/mL prior digestion, but all digested fractions exhibited similar antiproliferative activities (mean IC50 = 814 μg/mL). Oxidative DNA damage in cells was also attenuated by the treatments (200 μg/mL, 24 h preincubation), with all colonic fermented fractions displaying similar genoprotective action. These results suggest the potential of red wine pomace seasonings as chemopreventive agents in colorectal cancer.

Antimutagenic potentials of flavonoids from Achillea millefolium L. subsp. millefolium

Current researches have showed that cancer is one of the most widespread diseases in the world and there is a strong connection between its formation and mutagenesis. This has attracted attention toward mutation-focused researches to get better understanding, and finding new molecules with antimutagenic potential is a key concept for prevention of the hazardous effects of mutagens [1]. The genus Achillea L. (Asteraceae) comprises 85 species worldwide and 50 species in the flora of Turkey with more than 50% endemism [2]. In the present study we investigated the mutagenic and antimutagenic potentials of flavonoids isolated from Achillea millefolium L. subsp. millefolium by using Ames/Salmonella and E. coli WP2 bacterial test systems [3]. Four active compounds were isolated from the aerial parts of the plant and identified as luteolin, apigenin 7-O-β-D-glucoside, luteolin 7-O-β-D-glucoside and 6-OH-luteolin 7-O-β-D-glucoside by using a combination of extensive spectroscopic analysis and chemical methods. All of these compounds showed significant antigenotoxic activity against the positive mutagens MNNG and 9-AA. The inhibition rates ranged from 26.7% (luteolin 7-O-β-D-glucoside-3µM/plate) to 39.3% (luteolin-5µM/plate) for MNNG induced mutagenesis in E. coli WP2uvrA, and from 27.4% (apigenin 7-O-β-D-glucoside-4µM/plate) to 34.2% (apigenin 7-O-β-D-glucoside-5µM/plate) for 9-AA induced mutagenesis in S. typhimurium TA1537. 25 – 40% inhibition was defined as moderate antimutagenicity; 40% or more inhibition as strong antimutagenicity; and 25% or less inhibition as no antimutagenicity [4].

Novel colon-available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro.

Ileostomy studies provide a unique insight into digestion of food, allowing identification of physiologically relevant dietary phytochemicals and their metabolites important to gut health. We previously reported the consistent increase of components in ileal fluids of ileostomates after consumption of raspberries with use of nontargeted LC-MSn techniques and data deconvolution software highlighting two major unknown components (m/z 355 and 679). In-depth LC-MSn analyses suggested that the ileal m/z 355 components were p-coumaroyl glucarates. These compounds have not been identified previously and were confirmed in raspberry extracts after partial purification. The major ileal component with m/z 679 was a glycoside with an aglycone of m/z 517 and was present as two peaks in extracts of whole puree, unseeded puree, and isolated seeds. These components were purified using Sephadex LH20 and C18 SPE units and identified as major, novel raspberry triterpenoid glycosides. This triterpenoid-enriched fraction (100 nM) protected against H2 O2 -induced DNA damage in both colon cancer and normal cell lines and altered expression of cytoprotective genes. The presence of these novel raspberry triterpenoid components in ileal fluids indicates that they would be colon-available in vivo, so confirmation of their anticancer bioactivities is of key physiological relevance.

Phenolic Characterisation and Antioxidant Activity of Primula vulgaris and Its Antigenotoxic Effect on Fibroblast Cells

Background: Primula vulgaris has been used in traditional treatment, and its biological functions are attributed to its polyphenolics content. Objectives: The aim of this study was to determine the phenolics composition and the antioxidant activity of water extract of P. vulgaris (WEP) and to determine its probable preventive effects against H2O2-induced DNA damage in human fibroblast cells. Methods: The total polyphenolic content (TPC), ferric reducing antioxidant power (FRAP), and radical scavenging activity of WEP were determined using spectrophotometric methods. Phenolic compounds and antigenotoxic effects of WEP were evaluated using HPLC and comet assay, respectively. Results: The TPC and FRAP values of WEP were 15.023 ± 0.84 mg gallic acid and 82.63 ± 0.31 μM trolox per g sample, respectively. ρ-coumaric acid and rutin were detected as major phenolics. Moreover, WEP reduced H2O2-induced DNA damage in a concentration dependent manner in fibroblast cells compared to the positive controls (only 20 μM H2O2 treatment). Conclusions: Primula vulgaris can be used in food, cosmetics, and drug industries because of its antioxidant and antigenotoxic activities.

Phenolic Characterisation and Antioxidant Activity of Primula vulgaris and Its Antigenotoxic Effect on Fibroblast Cells

Background: Primula vulgaris has been used in traditional treatment, and its biological functions are attributed to its polyphenolics content. Objectives: The aim of this study was to determine the phenolics composition and the antioxidant activity of water extract of P. vulgaris (WEP) and to determine its probable preventive effects against H2O2-induced DNA damage in human fibroblast cells. Methods: The total polyphenolic content (TPC), ferric reducing antioxidant power (FRAP), and radical scavenging activity of WEP were determined using spectrophotometric methods. Phenolic compounds and antigenotoxic effects of WEP were evaluated using HPLC and comet assay, respectively. Results: The TPC and FRAP values of WEP were 15.023 ± 0.84 mg gallic acid and 82.63 ± 0.31 μM trolox per g sample, respectively. ρ-coumaric acid and rutin were detected as major phenolics. Moreover, WEP reduced H2O2-induced DNA damage in a concentration dependent manner in fibroblast cells compared to the positive controls (only 20 μM H2O2 treatment). Conclusions: Primula vulgaris can be used in food, cosmetics, and drug industries because of its antioxidant and antigenotoxic activities.

Testing of Schefflera vinosa extract in mammalian cells in vitro and in vivo for potential toxicity, genetic damage, and role of oxidation

ABSTRACTThe aim of this study was to examine the cytotoxic and genotoxic potential of a hydroethanolic extract of Schefflera vinosa (SV), a plant with schistosomicidal activity, as well as its influence on DNA damage induced by different mutagens, methyl methane sulfonate (MMS) and hydrogen peroxide (H2O2), in V79 cells and Swiss mice. Schefflera vinosa extract produced cytotoxicity at concentrations of 312.5 µg/ml or higher using the XTT cell proliferation assay kit. Treatment of V79 cell cultures with the highest SV concentration tested (150 µg/ml) significantly increased the frequency of micronuclei (MN) compared to controls. All SV concentrations significantly reduced the frequency of MN induced by hydrogen peroxide in V79 cell cultures. Further, SV was able to scavenge free radicals in the DPPH assay. In the in vivo test system, treatment with the highest dose tested (1,000 mg/kg body weight) induced a significant rise in frequency of DNA damage using the comet assay. However, animals treated with different doses of SV demonstrated absence of genotoxicity in the bone marrow MN test. For assessment of modulatory effects, the lower concentration of SV (250 mg/kg body weight) administered to MMS-treated mice significantly reduced frequency of DNA damage compared to the positive control (MMS alone). In contrast, the highest concentration tested (1,000 mg/kg body weight) significantly increased the rate of MN induced by MMS. The lack of genotoxic damage at biologically relevant SV concentrations, as well as the SV-mediated antigenotoxic and antioxidant activities, indicate the potential therapeutic usefulness of this plant extract. These activities may be attributed, at least in part, to the flavonoid quercitrin, its major component.

Antioxidant and antigenotoxic potencies of Sempervivum armenum on human lymphocytes in vitro.

In this research, the genotoxic and antigenotoxic effects of methanol extract of Sempervivum armenum (MSA) were studied using micronucleus (MN) test and sister chromatid exchange (SCE) test systems in cultured human peripheral blood cells. According to the SCE and MN tests results, MSA reduced the genotoxic effects of aflatoxin B1. In order to explain the reason for the antigenotoxic effects of MSA, antioxidants levels were determined. Cotreatments of 5, 10, 20mg/mL concentrations of MSA with aflatoxin B1 decreased the frequencies of SCE, MN and the malondialdehyde level and increased the amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The results of this experiment showed that MSA has strong antioxidative and antigenotoxic effects and this antigenotoxic activities of MSA can be due to the antioxidant activities.

Antimutagenic and antioxidant properties of the aqueous extracts of organic and conventional grapevine Vitis labrusca cv. Isabella leaves in V79 cells

ABSTRACTGrapes are one of the most commonly consumed fruit, in both fresh and processed forms; however, a significant amount is disposed of in the environment. Searching for a use of this waste, the antigenotoxic, antimutagenic, and antioxidant activities of aqueous extracts from organic and conventional Vitis labrusca leaves were determined using V79 cells as model. The antigenotoxic activity was analyzed by the alkaline comet assay using endonuclease III and formamidopyrimidine DNA glycosylase enzymes. The antimutagenic property was assessed through the micronucleus (MN) formation, and antioxidant activities were assessed using 2’,7’-dichlorodihydrofluorescin diacetate (DCFH-DA) assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH●) radical scavenging, as well as with superoxide dismutase (SOD) and catalase (CAT) activity assays. In addition, phenolic content and ascorbic acid levels of both extracts were determined. Data showed that both organic and conventional grapevine leaves extracts possessed antigenotoxic and antimutagenic properties. The extract of organic leaves significantly reduced intracellular reactive oxygen species (ROS) levels in V79 cells, and displayed greater ability for DPPH● scavenging and higher SOD and CAT activities than extract from conventional leaves. Further, the extract from organic leaves contained higher phenolic and ascorbic acid concentrations. In summary, extracts from organic and conventional grape leaves induced important in vitro biological effects.

Protective effects of Solanum cernuum extract against chromosomal and genomic damage induced by methyl methanesulfonate in Swiss mice.

Solanum cernuum Vell is a Brazilian shrub or small tree, restricted to Southeast states of the country. The leaves are commercialized as "panacéia" and indicated for the treatment of urinary disorders, gonorrhea, scabies, skin diseases and as desobstruent, diuretic and antiarrhythmic. The hydroalcholic extract is active in the treatment of gastric ulcer. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of S. cernuum hydroalcoholic extract (SC) in Swiss mice by micronucleus and comet assays. The animals were treated by gavage with the doses of 500, 1000 and 2000mg/kg body weight (b.w.). For antigenotoxicity assessment, the doses of 15, 30, 60, 120 and 240mg/kg b.w SC were administered simultaneously with the mutagen methyl methanesulfonate (MMS, 40mg/kg b.w., i.p.). The results showed that the SC was not genotoxic in both micronucleus and comet assays. On the other hand, the treatment with the lowest dose of SC (15mg/kg b.w.) plus MMS showed a statistically significant reduction in the frequency of micronuclei compared to treatment only with MMS. For the comet assay, significant reduction in extensions of DNA damage was observed in all treatments with SC combined with MMS in comparison with only MMS. The antigenotoxic activity observed for the SC may be due to the antioxidant potential of the compounds present in the extract such as guanidine alkaloids and flavonoids.

Protective effects of three luteolin derivatives on aflatoxin B1-induced genotoxicity on human blood cells

In the present study, we aimed to investigate the genotoxic and anti-genotoxic potencies of three luteolin derivatives (luteolin-7-O-glucoside, luteolin-7-O-rutinoside and luteolin-7-O-glucuronide) by using human cells. In the micronucleus test, the human lymphocytes were exposed to aflatoxin B1, the luteolin derivatives and a mixture of the two for 72 h. Furthermore, we have evaluated the levels of antioxidants of human whole blood plasma in order to clarify the possible mechanisms that may contribute to the anti-genotoxic activity of the luteolin derivatives. According to the results obtained from the micronucleus test, the highest protection rates for luteolin-7-O-glucoside, luteolin-7-O-rutinoside and luteolin-7-O-glucuronide against aflatoxin B1 were 32.09, 35.55 and 37.50 %, respectively. Similarly, these three luteolin derivatives ameliorated the level of antioxidants altered from aflatoxin B1.

Genoprotection and Cytotoxicity of Cassia surattensis Seed Extract on Vero Cell Evaluated by Comet and Cytotoxicity Assays

Cassia (C.) surattensis Burm. f. (Leguminosae) is a flowering plant that has been traditionally used in many countries for food and medicinal purposes. The present study was conducted to determine in vitro cytotoxicity and anti-genotoxic activity of the seed extract of C. surattensis. The cytotoxic and anti-genotoxic activities were evaluated against Vero cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and comet assays. In vitro cytotoxicity evaluation demonstrated that seed extract of C. surattensis was non-cytotoxic against the Vero cells. The 50 % cytotoxic concentration (CC50) value from MTT cytotoxicity assay was 332.87 µg/ml. The seed extract of C. surattensis exhibited strong inhibitory effects against H2O2-mediated DNA damage in Vero cells as observed in Comet assay. The presence of antioxidant activity in the seed extract was associated with the antigenotoxic property of C. surattensis. In summary, the present study demonstrated an efficient antigenotoxic property of C. surattensis, which is significant for future investigation for human applications.

Antimutagenic, Antigenotoxic, and Anticytotoxic Activities of Silybum Marianum [L.] Gaertn Assessed by the Salmonella Mutagenicity Assay (Ames Test) and the Micronucleus Test in Mice Bone Marrow

ABSTRACTSilymarin (SM), a standardized extract from Silybum marianum (L.) Gaertn., is composed mainly of flavonolignans, and silibinin (SB) is its major active constituent. The present study aimed to evaluate the antimutagenic activities of SM and SB using the Ames mutagenicity test in Salmonella Typhimurium, as well as their anticytotoxic and antigenotoxic activities using the mouse bone marrow micronucleus test. To assess antimutagenicity, Salmonella Typhimurium strains were treated with different concentrations of SM or SB and the appropriate positive control for each strain. To assess antigenotoxicity and anticytotoxicity, Swiss mice were treated with different concentrations of SM or SB and mitomycin C (MMC). The results showed that SM was not significantly effective in reducing the number of frameshift mutations in strain TA98, while SB demonstrated significant protection at higher doses (P < 0.05). Regarding strain TA 100, SM and SB significantly decreased mutagenicity (point mutations) (P < 0.05). The results of the antigenotoxic evaluation demonstrated that SM and SB significantly reduced the frequency of micronucleated polychromatic erythrocytes (MNPCE) (P < 0.05). The results also indicated that SM and SB significantly attenuated MMC-induced cytotoxicity (P < 0.05). Based on these results, both SM and SB presented antimutagenic, antigenotoxic, and anticytotoxic actions.

Therapeutic Potential of Essential Oils Focusing on Diterpenes.

Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health-consumption deportment. Previous studies revealed that diterpenes have antioxidant, antimicrobial, antiviral, antiprotozoal, cytotoxic, anticancer, antigenotoxic, antimutagenic, chemopreventive, antiinflammatory, antinociceptive, immunostimulatory, organoprotective, antidiabetic, lipid-lowering, antiallergic, antiplatelet, antithrombotic, and antitoxin activities. In conclusion, diterpenes may be an immense featuring concern in pharmaceutical consumption from a drug discovery point of view. Copyright © 2016 John Wiley & Sons, Ltd.

In vitro cytotoxicity, genotoxicity and antigenotoxicity assessment of Solanum lycocarpum hydroalcoholic extract

Context: Solanum lycocarpum A. St.-Hil. (Solanaceae), popularly known as ‘fruta-do-lobo’ (wolf fruit), ‘lobeira’ and ‘jurubebão’, is commonly used by native people of Central Brazil in powder form or as a hydroalcoholic extract for the management of diabetes and obesity and to decrease cholesterol levels. Objective: The present study determines the possible cytotoxic, genotoxic and antigenotoxic activities of hydroalcoholic extract of the S. lycocarpum fruits (SL).Materials and methods: The clonogenic efficiency assay was used to determine the cytotoxicity. Three concentrations of SL (16, 32 and 64 μg/mL) were used for the evaluation of its genotoxic and antigenotoxic potential on V79 cells using the micronucleus and comet assays. In the antigenotoxicity assays, the cells were treated simultaneously with SL and the alkylating agent methyl methanesulphonate (MMS, 44 μg/mL for the micronucleus assay and 22 μg/mL for the comet assay) as an inducer of micronuclei and DNA damage.Results: The results showed that SL was cytotoxic at concentrations up to 64 μg/mL. No significant differences in the rate of chromosome or DNA damage were observed between cultures treated with SL and the control group. In addition, the frequencies of micronuclei and DNA damage induced by MMS were significantly reduced after treatment with SL. The damage reduction percentage ranged from 68.1% to 79.2% and 12.1% to 16.5% for micronucleus and comet assays, respectively.Discussion and conclusion: SL exerted no genotoxic effect and exhibited chemopreventive activity against both genomic and chromosome damage induced by MMS.

Vernonanthura polyanthes leaves aqueous extract enhances doxorubicin genotoxicity in somatic cells of Drosophila melanogaster and presents no antifungal activity against Candida spp.

Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (Asteraceae), known as "assa-peixe", has been used in ethnomedicine for the treatment of various diseases such as bronchitis, pneumonia, hemoptysis, persistent cough, internal abscesses, gastric and kidney stone pain. Moreover, some studies demonstrated that species of Genus Vernonia present antifungal activity. Due to the biological relevance of this species, the aim of this study was to investigate the toxic, genotoxic, antigenotoxic and antifungal potential of V. polyanthes leaves aqueous extract in somatic cells of Drosophila melanogaster or against Candida spp. The aqueous extract of the plant showed no toxic, genotoxic and antigenotoxic activity in the experimental conditions tested using the wing somatic mutation and recombination test (SMART/wing). However, when the extract was associated with doxorubicin, used in this work as a positive control, the mutagenic potential of doxorubicin was enhanced, increasing the number of mutations in D. melanogaster somatic cells. In the other hand, no inhibitory activity against Candida spp. was observed for V. polyanthes leaves aqueous extract using agar-well diffusion assay. More studies are necessary to reveal the components present in the V. polyanthes leaves aqueous extract that could contribute to potentiate the doxorubicin genotoxicity.

Isolation and characterization of flavanols from Anthocephalus cadamba and evaluation of their antioxidant, antigenotoxic, cytotoxic and COX-2 inhibitory activities

In search of lead molecules for use in disease prevention and as food additive from natural sources, two flavanols were isolated from leaves of Anthocephalus cadamba (Roxb.) Miq., Rubiaceae. Their structures were established as 6-hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin and 6-hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin-(4⿿6⿴)-(⿿)-epicatechin on the basis of spectroscopic data. Both the compounds exhibited potent antioxidant and antigenotoxic activity. 6-Hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin scavenged DPPH, ABTS+.and superoxide anion radicals with IC50 values of 6.09μg/ml, 5.95μg/ml and 42.70μg/ml respectively whereas the IC50 values for 6-hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin-(4⿿6⿴)-(⿿)-epicatechin were 6.62μg/ml for DPPH free radicals, 6.93μg/ml for ABTS radical cations and 49.08μg/ml for superoxide anion radicals. Both the compounds also exhibited potent reducing potential in reducing power assay and protected the plasmid DNA (pBR322) against the attack of hydroxyl radicals generated by Fenton's reagent in DNA protection assay. In SOS chromotest, 6-hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin decreased the induction factor induced by 4NQO (20μg/ml) and aflatoxin B1 (20μg/ml) by 31.78% and 65.04% respectively at a concentration of 1000μg/ml. On the other hand, 6-hydroxycoumarin-(4⿳⿿8)-(⿿)-epicatechin-(4⿿6⿴)-(⿿)-epicatechin decreased the genotoxicity of these mutagens by 37.11% and 47.05% respectively. It also showed cytotoxicity in COLO-205 cancer cell line with GI50 of 435.71μg/ml. Both the compounds showed moderate cyclooxygenase-2 inhibitory activity.

Leaf extracts from Teucrium ramosissimum protect against DNA damage in human lymphoblast cell K562 and enhance antioxidant, antigenotoxic and antiproliferative activity.

The in vitro antioxidant, antigenotoxic and antiproliferative activities of Teucrium ramosissimum extracts were investigated. The antioxidant activities of the tested extracts were evaluated through three chemical assays: The Cupric reducing antioxidant capacity, the reducing power and the ferric reducing antioxidant power. TR1 fraction from methanol extract showed the best antioxidant activity evaluated by the CUPRAC, RP and FRAP assays with TEAC values of 4.04, 1.77 and 1.48μM respectively compared to control. Yet, TR2 fraction exhibited the lowest antioxidant effect with a TEAC values of 1.97, 0.408 and 0.35μM respectively. All the tested extracts were also found to be effective in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. Furthermore, the effects of T. ramosissimum extracts on cell proliferation were also examined. The cytotoxic study revealed that methanol extract significantly inhibited the proliferation of K562 cells (IC50=150μg/mL). The antigenotoxic properties of these extracts were investigated by assessing the induction and inhibition of the genotoxicity induced by the direct-acting mutagen, hydrogen peroxide (H2O2), using an eukaryotic system; the "Comet assay." The results showed that all the extracts inhibited the genotoxicity induced by H2O2, and particularly TR2 fraction (96.99%) and methanol extract (96.64%). The present study has demonstrated that T. ramosissimum extract possess potent antioxidant, antiproliferative and antigenotoxic activities, which could be derived from compounds such as flavonoids and polyphenols.