Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

In vitro chemopreventive and cytotoxic effects of Amazon mosses Leucobryum martianum (Hornsch.) and Leucobryum laevifolium (Broth) extracts.

Several bioactive compounds, such as polyphenols, demonstrate low toxicity and prominent effects on cancer cells with antioxidant, anti-inflammatory, and antitumor activities. Such compounds can be found in Amazon mosses Leucobryum martianum (Hornsch.) Hampe ex Müll. Hal. (Hornsch.) and Leucobryum laevifolium (Broth). Antimutagenic assay with Salmonella enterica serovar Typhimurium and cytotoxicity with different eukaryotic cell lines were carried out to screen aqueous, hydroalcoholic, and ethanolic extracts of those Amazon mosses for anticancer potential. The results indicate the capacity of all extracts of both mosses to exert chemopreventive effects against 4-nitroquinoline-N-oxide (4NQO) and 2-aminoanthracene (2-AA), which are direct or indirect mutagens. In particular, the ethanolic and aqueous extract from L. martianum. The ethanolic extract from L. martianum induces significant cytotoxicity by mitochondrial metabolism and cell membrane disruption pathways to tumor or non-tumor cells. The aqueous extract from L. martianum showed a mainly cytotoxic response in the HepG2 cells, a human liver carcinoma, reaching ~90% cytotoxicity. The same extract did not induce significant damage to normal liver cells (F C3H cells) by membrane interaction pathway. The selective cytotoxicity in the aqueous extract of L. martianum makes it a candidate against liver cancer. Further studies, including in vivo models, are necessary to validate the efficacy and safety of the aqueous extract of L. martianum.

Chemical characterization of Brazilian savannah Byrsonima species (muricis) and their impact on genomic instability and chemopreventive effects.

The identification of new drugs with few or no adverse effects is of great interest worldwide. In cancer therapy, natural products have been used as chemopreventive and chemotherapeutic agents. Plants from the Brazilian savannah belonging to the Byrsonima genus are popularly known as muricis and have attracted much attention due to their various pharmacological activities. However, there are currently no data on these plants concerning their use as chemopreventive or chemotherapeutic agents in human cell lines. The present study assessed the potential of B. correifolia, B. verbascifolia, B. crassifolia, and B. intermedia extracts as natural alternatives in the prevention and/or treatment of cancer. The chemical constituents present in each extract were analyzed by electrospray ionization-mass spectrometry (ESI-MSN). The mutagenic/antimutagenic (micronucleus assay), genotoxic/antigenotoxic (comet assay), apoptotic/necrotic (acridine orange/ethidium bromide uptake), and oxidative/antioxidative (CM-H2DCFDA) effects of the extracts and their influence on gene expression (RTqPCR) were investigated in nonmetabolizing gastric (MNP01) and metabolizing hepatocarcinoma (HepG2) epithelial cells to evaluate the effects of metabolism on the biological activities of the extracts. The genotoxicity, mutagenicity, and apoptotic effects observed in HepG2 cells with B. correifolia and B. verbascifolia extracts are probably associated with the presence of proanthocyanidins and amentoflavone. In MNP01 cells, none of the four extracts showed mutagenic effects. B. crassifolia and B. intermedia extracts exhibited strong antimutagenicity and enhanced detoxification in HepG2 cells and antioxidant capacities in both types of cells, possibly due to the presence of gallic and quinic acids, which possess chemopreventive properties. This study identifies for the first time B. correifolia and B. verbascifolia extracts as potential agents against hepatocarcinoma and B. crassifolia and B. intermedia extracts as putative chemopreventive agents.

Pistacia lentiscus L. fruits showed promising antimutagenic and antigenotoxic activity using both in-vitro and in-vivo test systems.

Pistacia lentiscus L. is one of the most popular medicinal plants attributed to its beneficial properties on human health. However, few toxicogenetic studies have been carried out. Therefore, the aim of this study was to examine the potential genotoxic/antigenotoxic and mutagenic/antimutagenic properties of oil, ethyl acetate and ethanolic extracts of P. lentiscus L. fruits using in vitro the Ames and Umu assays, as well as in vivo micronucleus (MN) test. Extracts did not exert any significant mutagenic/genotoxic effects but provided protection against standard mutagenic and genotoxic agents including 2 nitrofluorene (2-NF) at 2.5 and 5 µg/ml; sodium azide at 5 and 10 µg/ml; 3-methylcholanthrene (3-MC) at 25 and 50 µg/ml; cyclophosphamide (CP) at 50 and 100 µg/ml; 4-nitroquinoline 1-oxide (4-NQO) at 0.05 µg/ml and 2-amino-anthracene (AA) at 0.2 µg/ml. Further, cytotoxicity and selectivity were examined on human hepatocarcinoma (HepG2), and MCF-7 breast cancer cell lines as well as a human normal-like fibroblast cell line (TelCOFS02MA) using MTT assay. Among all extracts, PF1 (ethanolic) showed the most significant selectivity index (SI) (HepG2:11.98; MCF7:4.83), which led to further investigations using an animal model. Oral administration of PF1 (125-1000 mg/kg b.w.) significantly decreased the number of micronucleated cells in CP -initiated (50 mg/kg b.w.) mice, while the number of micronucleated reticulocytes (MNRET), micronucleated polychromatic erythrocytes (MNPCE) or mitotic index (MI) were not markedly affected. Further, PF1 significantly enhanced catalase (CAT) and superoxide dismutase (SOD) activities in the livers and kidneys of these animals. The obtained results indicated the beneficial properties of P. lentiscus L. fruits for use in therapy against harmful effects of genotoxic and mutagenic agents. However, while promising it should be noted that the obtained results are preliminary and need to be confirmed prior to therapeutic use.

Anticlastogenic, antimutagenic, and cytoprotective properties of Orthosiphon stamineus ethanolic leaves extract.

Orthosiphon stamineus (O.S) is widely consumed for its medidcinal value including anti-inflammatory, anti-infective, and diuretic properties. The present study evaluates the cytoprotective, anti-mutagenic, and anticlastogenic efficacies of standardized extract of Orthosiphon stamineus. Normal liver cell line (WRL68) exposed to hydrogen peroxide and serum-deprived media as insults to evaluate cytoprotective and glutathione activation activities of (Et. O. s). Salmonella typhimurium TA98 and TA100 exposed to different concentrations of (Et. O. s). The influence of Et. O. s on mitotic, replicative indices as well as chromosomal aberration (CA) and sister chromatid exchange (SCE) induced in human peripheral blood lymphocytes by mitomycin C (MMC). The Et. O.s proved to be a potent scavenger for hydrogen peroxide and other free radicals in serum-depraved media, which showed to stimulate glutathione production in liver cells line. Moreover, it did not induce mutations in S. typhimurium subspecies TA98 and TA100. The standardized extract exhibited powerful antimutagenic activities as verified against both 2-nitrofluorene and sodium azide in S. typhimurium TA98 and TA100 cells, respectively. Cytogenetic tests showed high concentrations of Et. O. s to reduce the values of mitotic and replicative indices without any accompanying side effects, such as chromosomal abnormalities or SCE. To ameliorate MMC effects, pretreatment with the extract proofed to be efficient protocol. These data suggests that O. stamineus extract could be useful as cytoprotective, antimutagenic, and anticlastogenic efficacies, which owes to its potent chemoprevention, antioxidant, and glutathione activation properties.

A perspective review on medicinal plant resources for their antimutagenic potentials.

Mutagens present in the environment manifest toxic effects and are considered as serious threat for human health and healthcare. Recent reports reveal that medicinal plant resources are being explored for identifying potent antimutagenic as well as cancer preventing agents. There is mounting evidence that cancer and other mutation-related diseases can be prevented with the use of medicinal pant resources including crude extracts, active fractions, phytochemicals, and pure phytomolecules. These medicinal plant resources possessing antimutagenic potentials have been shown to target molecular mechanisms underlying the mutagenic impacts. Technological advents and high-throughput screening/activity methods have revolutionized this field, though several potent plants and their active principles have been reported as effective antimutagens. The translational success rate needs to be improved, but the trends are encouraging. In this review, we present the current understandings and updates on various mutagens in the environment, toxicities related/attributed to them, the resultant mutations (and cancer), and how medicinal plants come to the rescue. A perspective review has been presented on whether and how medicinal plant resources can be an effective approach for addressing mutagens in the environment. An account of medicinal plant resources used as antimutagenic agents has been given along with the underlying mechanism of action and their therapeutic potential in various models of cancer. Recent success stories, current challenges, and future prospects are discussed.

Pedunculagin isolated from Plinia cauliflora seeds exhibits genotoxic, antigenotoxic and cytotoxic effects in bacteria and human lymphocytes.

Pedunculagin (PD), an ellagitannin found in different plant species, possesses several pharmaceutical properties, including antitumor, antioxidant, gastroprotective, hepatoprotective, and anti-inflammatory properties. However, the effects of PD alone on DNA remain to be determined. The aim of this study was to investigate the potential cytotoxic, genotoxic, and antigenotoxic activities of PD isolated from Plinia cauliflora seeds using in silico and in vitro assays. To elucidate the biological activities of PD, in silico tools indicative of antioxidant, antineoplastic, and chemopreventive activities of PD were used. Subsequently, the mutagenic/antimutagenic effects of PD were later assessed using bacteria with the Ames test, and the cytotoxic, genotoxic, and antigenotoxic effects utilizing human lymphocytes as evidenced by trypan blue exclusion test and CometChip assay. In silico analysis indicated potential antioxidant, chemopreventive, free radical scavenger, and cytostatic activities of PD. In the Ames test, PD was found to be not mutagenic; however, this plant component protected DNA against damage-mediated by mutagens 4-nitroquinoline-1-oxide and sodium azide. Regarding human lymphocytes, PD alone was cytotoxic and genotoxic; however, it also reduced DNA damage induced by doxorubicin at co- and post-treatment. In conclusion, PD showed genotoxic, antigenotoxic and cytotoxic effects in human lymphocytes and antimutagenic effects in bacteria.

In vivo assessment of antioxidant, antigenotoxic, and antimutagenic effects of bark ethanolic extract from Spondias purpurea L.

Medicinal plants have always been used for therapeutic purposes; however, some plants may contain toxic and mutagenic substances. The aim of this study was to assess the cytotoxic, genotoxic, mutagenic, antioxidant, antigenotoxic, and antimutagenic effects of the bark ethanolic extract of Spondias purpurea L. using male and female Swiss albino mice. To determine the protective effects of the extract, benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) were selected as cell damage inducers. The extract was examined at doses of 500, 1000, or 1500 mg/kg body weight (BW)via gavage alone or concomitant with B[a]P or CP. Oxidative stress was measured by quantification of blood catalase activity (CAT), reduced glutathione (GSH) levels in total blood, liver, and kidney, and concentrations of malondiadehyde (MDA) in liver and kidney. Genotoxicity and antigenotoxicity were evaluated by the comet assay using peripheral blood. Cytotoxicity, mutagenicity, and antimutagenicity were determined utilizing the micronucleus test in bone marrow and peripheral blood. The S. purpurea L extract increased CAT activity and GSH levels accompanied by a decrease in MDA levels after treatment with B[a]P and CP. No genotoxic, cytotoxic, or mutagenic effects were found in mice exposed only to the extract. These results indicate that the extract of S. purpurea exhibited protective effects against oxidative and DNA damage induced by B[a]P and CP.

Anti-genotoxic and anti-mutagenic effects of melatonin supplementation in a mouse model of melanoma.

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.

Antiproliferative, apoptotic, and antimutagenic properties of stem bark and seed fractions of Polyalthia cerasoides (Roxb.).

AIMS: The aim was to compare the anticancer and antimutagenic potency of Polyalthia cerasoides seeds and stem bark. AIM OF THE STUDY: The aim of this study was to investigate the antiproliferative, apoptotic, antioxidation to DNA, and antimutagenic activity of alcoholic (PS-1 and PS-3) and petroleum ether (PS-2 and PS-4) stem bark and seed fractions of P. cerasoides. METHODS: P. cerasoides stem bark and seeds were extracted with ethanol: water mixture (9:1 ratio v: v) and fractionated with petroleum ether. Fractions were investigated for antiproliferative effect using cell by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole assay (cell line used liver [HepG2] and cervical [HeLa] cancer cell lines), DNA damage protection using hydroxyl radical and antimutagenic effect using chromosome aberration test. RESULTS: PS-1 (IC50 10 µg/ml) and PS-3 (IC50 11 µg/ml) showed maximum antiproliferative activity against HepG2 cell lines, whereas, PS-1 (IC50 10 µg/ml), PS-2 (IC50 24 µg/ml), and PS-3 (IC50 11 µg/ml) showed better antiproliferative activity against HeLa cell lines. PS-3 and PS-4 were protective against oxidation to the supercoiled DNA molecule. Further, petroleum ether extract of both seed (PS-2) and stem bark (PS-4) showed good antimutagenicity as revealed by the less chromosomal aberrations compared to PS-1 and PS-3 fractions. CONCLUSIONS: This study demonstrated the beneficial effect of fractions against oxidation of DNA, antiproliferative, apoptotic, and antimutagenic activity. Probably, this property would be attributable by their phenolic and steroid constituents. Therefore, this plant could be used as a potential source of nutraceutical agents.

Antimutagenic Effects of the Composition from Green Tea Leaves Extracts and Caucasian Persimmon Fruits.

On a culture of human peripheral blood lymphocytes, antimutagenic activity of a composition from extracts of green tea leaves and Caucasian persimmon fruits was established with a modification of the mutation process induced by chemical compounds producing an alkylating effect (nitrosomethylurea and sodium fluoride). A concentration dependence of the antimutagenic efficiency of the studied phytocomposite was shown. The highest antimutagenic efficiency was observed when a combination of green tea extract at a concentration of 0.01 µg/ml and persimmon fruit extract at a concentration of 0.001 µg/ml were used. Moreover, this combination was most effective against mutations induced by both nitrosomethylurea and sodium fluoride: the antimutagen efficiency factor was 0.53 and 0.55, respectively.

Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of Zanthoxylum schinifolium Fruit and Pericarp.

The fruit and pericarp of Zanthoxylum schinifolium (ZS) have been used in traditional medicine; however, few studies have characterized ZS fruit and pericarp. Therefore, in the present study, we evaluated the safety of ZS fruit (ZSF) and pericarp (ZSP) extracts and compared their bioactivity. To evaluate the safety of ZSF and ZSP, mutagenicity, cytotoxicity, and oxidative stress assays were performed and nontoxic concentration ranges were obtained. ZSP was found to be superior to ZSF in terms of its antimutagenic, antioxidant, and anti-inflammatory activities. In the S9 mix, the mutation inhibition rate of ZSP was close to 100% at concentrations exceeding 625 µg·plate-1 for both the TA98 and TA100 strains. ZSP exhibited efficient DPPH (IC50 = 75.6 ± 6.1 µg·mL-1) and ABTS (IC50 = 57.4 ± 6 µg·mL-1) scavenging activities. ZSP inhibited the release of cytokines, involved in IL-1ß (IC50 = 134.4 ± 7.8), IL-6 (IC50 = 262.8 ± 11.2), and TNF-α (IC50 = 223.8 ± 5.8). These results indicate that ZSP contains a higher amount of biochemicals than ZSF, or that ZSP contains unique biochemicals. In conclusion, for certain physiological activities, the use of ZSP alone may be more beneficial than the combined use of ZSF and ZSP.

Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models.

The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.

Nutraceutical Potential of Leaf Hydro-Ethanolic Extract of the Edible Halophyte Crithmum maritimum L.

Aromatic halophytes represent an exceptional source of natural bioactive compounds for the food industry. Crithmum maritimum L., also known as sea fennel, is a halophyte plant colonizing cliffs and coastal dunes along Mediterranean and Atlantic coasts. It is well known to produce essential oils and polyphenols endowed with antioxidant and biological effects. The present work reports the phytochemical profile, as well as antioxidant, antimicrobial and antimutagenic properties of C. maritimum leaf hydro-alcoholic extract. From LC-ESI-MS analysis, eighteen phenolic compounds were depicted in sea fennel extract and the amount of total phenolic content exceeds 3% DW. Accordingly, C. maritimum extract showed strong antioxidant activities, as evidenced by in vitro (DPPH, ORAC, FRAP) and ex vivo (CAA-RBC and hemolysis) assays. An important antimicrobial activity against pathogenic strains was found as well as a strong capacity to inhibit Staphylococcus aureus (ATCC 35556) biofilm formation. Sea fennel extracts showed a significant decrease of mutagenesis induced by hydrogen peroxide (H2O2) and menadione (ME) in Saccharomyces cerevisiae D7 strain. In conclusion, our results show that C. maritimum is an exceptional source of bioactive components and exert beneficial effects against oxidative or mutagenic mechanisms, and pathogenic bacteria, making it a potential functional food.

Protective Effect of Nigella sativa and Nigella damascena Fixed Oils Against Aflatoxin Induced Mutagenicity in the Classical and Modified Ames Test.

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography-mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2 . The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.

A comprehensive assessment of the chemical composition, antioxidant, genoprotective and antigenotoxic activities of Lamiaceae species using different experimental models in vitro.

This research was aimed to assess the potential of Glechoma hederacea, Hyssopus officinalis, Lavandula angustifolia, Leonurus cardiaca, Marrubium vulgare and Sideritis scardica (Lamiaceae) methanolic, ethanolic and aqueous extracts against the damaging effects of oxidative stress using different experimental models. The chemical characterization was done spectrophotometrically by quantifying total phenolics, phenolic acids, flavonoids and flavonols in the extracts, as well as by employing HPLC-DAD technique. Moreover, DPPH assay was used to assess the extracts' radical scavenging potential. Genoprotective properties of the extracts were evaluated using plasmid pUC19 Escherichia coli XL1-Blue, whereas their antigenotoxic potential was determined using Salmonella typhimurium TA1535/pSK1002 and normal human lung fibroblasts. All of the extracts showed antioxidant activity in DPPH assay. Furthermore, the results have shown that aqueous extracts provided the best protection for plasmid DNA, while alcoholic extracts most effectively contributed to the preservation of prokaryotic DNA. Additionally, each of the tested samples significantly protected the eukaryotic cells against genomic damages. Finally, despite not showing exceptional results in DPPH assay, S. scardica extracts are regarded as the most favorable in maintaining the integrity of DNA, which might be due to high quantities of phenolics such as quercetin (up to 17.95 mg g-1), naringin (up to 5.07 mg g-1) and luteolin-7-O-glucoside (up to 3.54 mg g-1). Overall, this comprehensive concept highlights the ability of these Lamiaceae species to safeguard the DNA from reactive oxygen species, to curtail the inflicted damage and also improve the efficiency of the DNA repair mechanisms, while emphasizing the importance of polyphenols as their active principles.

Morus alba Prevented the Cyclophosphamide Induced Somatic and Germinal Cell Damage in Male Rats by Ameliorating the Antioxidant Enzyme Levels.

Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy.

A novel combined bioactivity / chemoactivity holistic approach for the evaluation of dietary supplements.

There is increasing evidence that the excessive generation of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent from the harmful effects of free radicals on human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. In the first step, this approach includes in vitro studies to evaluate the antioxidant activity of the dietary supplements by measuring the parameters of free radical scavenging capacity, of reducing power activity, as well as, their ability to protect biomolecules from oxidation. Furthermore, the evaluation of their antimutagenic and antigenotoxic effects is also presented. SubsequentlySub, the specific effects of the dietary supplements were examined in three cancer cell lines (HepG2, HeLa, MKN45), by measuring redox biomarkers such as glutathione, reactive oxygen species and thiobarbituric acid reactive substances, using flow cytometry and spectrophotometry. Our results indicate that all the dietary supplements exhibit high antioxidant, antimutagenic, antigenotoxic and lipid protective activity. The most prominent result is their capability to induce oxidative damage on cancer cells via the critical decrease of the levels of their intracellular glutathione, as well as the increase of ROS and lipid peroxidation levels after the administration of non-cytotoxic concentrations. We suggest that the proposed methodology could constitute a valuable tool for the characterization of dietary supplements based on their chemical and functional properties.

Antimutagenic, Antiproliferative and Antioxidant Properties of Sea Grape Leaf Extract Fractions (Coccoloba uvifera L.).

BACKGROUND: Cancer is a disease characterized by the invasion and uncontrolled growth of cells. One of the best ways to minimize the harmful effects of mutagens is through the use of natural antimutagens. In this regard, the search for new antimutagens that act in the chemoprevention could represent a promising field in this area. OBJECTIVE: In this study biological potential of 11 fractions from Coccoloba uvifera L. leaf hexane extract was evaluated by several in vitro tests. METHODS: Leaves were lyophilized and hexane extraction was performed. The extract was fractionated by column chromatography with hexane, ethyl acetate, and methanol. The antimutagenic (Ames test), antiproliferative (MTT test), and antioxidant capacity (DPPH, ABTS, and ferrous ion chelation) of the fractions were evaluated. RESULTS: Fractions 4, 6, 8, and 9 have antimutagenic activity (against sodium azide in strain TA100), fraction 11 showed antiproliferative capacity (IC50 of 24 ± 9 µg/mL in cells of HCT 116). The fractions with the highest activity were analyzed by HPLC-MS and lupeol, acacetin, and ß-sitosterol were identified. CONCLUSION: This study demonstrates, for the first time, the bioactivity of C. uvifera leaf as a new source of High Biological Value Compounds (HBVC), which can be of interest to the food and pharmaceutical industries.

Colored Corn: An Up-Date on Metabolites Extraction, Health Implication, and Potential Use.

Colored (orange, pink, red, purple, and blue) corn strongly attracted attention on its healthy properties mainly due to its anthocyanin and carotenoid composition which is also responsible for its pigmentation. The present review summarized the recent updates on the extraction and chemical characterization of the main plant secondary metabolites present in colored seeds, kernel, cob, husk, and silk. The main approaches used to stabilize the extracts have been discussed as well as their food and non-food uses. Both in vitro and in vivo (animal models) studies on the different effects (antibacterial, antimutagenic, antioxidant, and anti-inflammatory activities, effects on metabolic syndrome, diabetes, glucose and lipidic metabolism, and neuroprotection) of pigmented extracts on animal and human health have been summarized.