The Relationship Between Neuroprotective Activity and Antigenotoxic and Acetylcholinesterase Inhibitory Effects of Glaucium corniculatum Extracts

Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it's protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.

Brown Flaxseed Prevents DNA Damage Induced by 1,2-Dimethylhydrazine in a Pre-Clinical Model

ABSTRACT The study evaluated the effects of brown flaxseed supplementation in natura on the prevention of DNA damage induced by 1,2-dimethylhydrazine (DMH) in vivo. The experimental groups were Negative and Positive Controls and the protocols of Pre-treatment, Simultaneous, Post-treatment, Pre+continuous in relation to the supplementation of brown flaxseed and administration with carcinogenic compound. The results showed that brown flaxseed supplementation does not cause genomic and genetic damage. In addition, brown flaxseed showed a chemopreventive food that reduced the damages assessed by the comet assay up to 94.07x and the damages assessed by the micronucleus assay up to 91.88x. Brown flaxseed supplementation also increased the frequency of monocytes and lymphocytes indicating immunological improvements. Thus, brown flaxseed supplementation is considered safe and reduces the frequency of DNA damage that can lead to tumors. Therefore, if these events are confirmed in humans, flaxseed will have reinforced its indication as a functional chemopreventive food in the prevention of cancer.

Avaliação fitoquímica e atividade antioxidante, antimutagênica e toxicológica do extrato aquoso das folhas de Ocimum gratissimum L / Phytochemical Assessment And Antioxidant, Antimutagenic And Toxicological Activity Of Ocimum gratissimum L. Leaf aqueous extract

A espécie Ocimum gratissimum L., popularmente conhecida como alfavaca, é uma planta muito usada na medicina tradicional brasileira, à qual são atribuídas diversas atividades terapêuticas quando usada na forma de infuso de suas folhas. Neste estudo foi realizada a caracterização fitoquímica, a avaliação da ação antioxidante e a investigação dos efeitos antimutagênico e antigenotóxico, além do efeito mutagênico e genotóxico potencial do extrato aquoso liofilizado a parir das folhas de O. gratissimum (EAOG). O conteúdo de polifenóis totais no extrato foi determinado pelo método Folin-Ciocalteu, sendo encontrado 11,3 µg EAG/mg de EAOG. A atividade antioxidante foi avaliada pelo teste do 1,1-difenil-2-picril hidrazil (DPPH•), apresentando IC50 de 83,0 µg/mL. A antimutagenicidade e mutagenicidade foram avaliadas em cepas de Salmonella typhimurium (TA98 e TA100) utilizando o teste Salmonella/microssoma (Salmonella typhimurium/microssomas) em diferentes concentrações. EAOG induziu a atividade antimutagênica para a cepa TA98. A mutagenicidade não foi observada para o extrato em ambas as linhagens. Adicionalmente, a ação antigenotoxica avaliada pelo teste de clivagem do DNA-plasmidial também foi observada para EAOG. Os resultados também demonstraram que o extrato não foi capaz de induzir a genotoxicidade pelo teste empregado. Este estudo relata, pela primeira vez, as propriedades antimutagênica e antigenotóxica do extrato aquoso de O. gratissimum.

The species Ocimum gratissimum L., popularly known as Clove Basil, is a plant widely used in traditional Brazilian medicine, and several therapeutic activities are attributed to it when used as infusion of its leaves. In this study, we carried out a phytochemical characterization and the assessment evaluation and investigation of the antioxidant action of the antimutagenic and antigenotoxic effects and the potential mutagenic and genotoxic effects of the freeze-dried aqueous extract of the O. gratissimum (EAOG) leaves. The total polyphenol content in the extract was determined by the Folin-Ciocalteu method, and we found 11.3 µg EAG/mg of EAOG. The antioxidant activity was assessed by the 1,1-diphenyl-2-picryl hidrazil (DPPH·), with IC50 of 83.0 µg/mL. Antimutagenicity and mutagenicity were assessed in Salmonella typhimurium (TA98 and TA100) strains using the Salmonella/microsome (Salmonella typhimurium/microsome) test in different concentrations. EAOG induced antimutagenic activity for strain TA98. Mutagenicity was not observed for the extract in both strains. Additionally, antigenotoxic action, assessed by cleavage of the DNA-damage, was also observed for EAOG. The results also show that the extract was not able to induce genotoxicity by the test used. This study reports for the first time the antimutagenic and antigenotoxic properties of the O. gratissimum aqueous extract.

Investigation of protective effects of Erythrina velutina extract against MMS induced damages in the root meristem cells of Allium cepa

Erythrina velutina Willd., Fabaceae, is a medicinal plant that can be found in the tropics and subtropics, including in the semi-arid northeastern Brazil. It is commonly used in folk medicine to treat anxiety, agitation and insomnia. E. velutina has been known to present analgesic, anti-inflammatory and antibacterial activities, however, it is unknown if this plant present a protective effect on DNA. We assessed the antigenotoxic effect of E. velutina against the genotoxic effects induced by MMS in the root meristem cells of Allium cepa. Three concentrations of the aqueous extract (100, 200 and 400 mg/L) of this medicinal plant were used in three different types of treatment (pre-, post- and simultaneous). The effects of the extracts on the root meristem cells of A. cepa were analyzed at both macroscopic and microscopic levels. Protective effects were observed at higher concentrations in pre-treatment and in simultaneous treatment. The results suggest that E. velutina may present antigenotoxic properties and demonstrate its chemopreventive potential.

Chemical composition and antigenotoxic properties of Lippia alba essential oils

The present work evaluated the chemical composition and the DNA protective effect of the essential oils (EOs) from Lippia alba against bleomycin-induced genotoxicity. EO constituents were determined by Gas Chromatography/Mass Spectrometric (GC-MS) analysis. The major compounds encountered being citral (33 percent geranial and 25 percent neral), geraniol (7 percent) and trans-β-caryophyllene (7 percent) for L. alba specimen COL512077, and carvone (38 percent), limonene (33 percent) and bicyclosesquiphellandrene (8 percent) for the other, COL512078. The genotoxicity and antigenotoxicity of EO and the compounds citral, carvone and limonene, were assayed using the SOS Chromotest in Escherichia coli. The EOs were not genotoxic in the SOS chromotest, but one of the major compound (limonene) showed genotoxicity at doses between 97 and 1549 mM. Both EOs protected bacterial cells against bleomycin-induced genotoxicity. Antigenotoxicity in the two L. alba chemotypes was related to the major compounds, citral and carvone, respectively. The results were discussed in relation to the chemopreventive potential of L. alba EOs and its major compounds.

Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice

Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as "erva-cidreira" or "melissa", it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance.

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Panax ginseng is one of the most widely prescribed herbal medicines for the treatment of cancer, diabetes, chronic inflammation, and neurodegenerative and cardiovascular diseases. Since the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions, we investigated the possible genotoxicity of a water-soluble form of the dry root of P. ginseng (2.5, 5.0 or 10.0 mg/mL) and its ability to protect against the genotoxicity of doxorubicin (DOX; 0.125 mg/mL) by using the Drosophila melanogaster wing somatic mutation and recombination test (SMART) with standard and high-bioactivation crosses of flies. Panax ginseng was not genotoxic at the concentrations tested, whereas DOX-induced genotoxicity in marker-heterozygous flies resulted mainly from mitotic recombination. At low concentrations, P. ginseng had antirecombinogenic activity that was independent of the concentration of extract used. Recombination events may promote cancer, but little is known about the ability of P. ginseng to inhibit such recombination or modulate DNA repair mechanisms.

Antigenotoxic effects of Mandevilla velutina (Gentianales, Apocynaceae) crude extract on cyclophosphamide-induced micronuclei in Swiss mice and urethane-induced somatic mutation and recombination in Drosophila melanogaster

A Mandevilla velutina crude extract was investigated using the mouse micronucleus test (MNT) and the Drosophila melanogaster somatic mutation and recombination test (SMART) using standard (ST) and high bioactivation (HB) crosses. The MNT used 10 mg, 20 mg or 40 mg per 100 g of body weight (bw) of extract with and without 0.2 mg per 100 g bw peritoneal cyclophosphamide. There was no genotoxicity in the negative control or extract only groups and, compared to the cyclophosphamide control, there was a significant reduction in micronucleated polychromatic erythrocytes in all the groups given extract plus cyclophosphamide. For SMART larvae were fed 5 or 10 mg mL-1 of extract for seven days with and without 0.89 mg mL-1 of urethane given on day seven. The ST and HB flies showed no significant differences in spots between the negative control and the extract only groups. The number of urethane-induced spots was reduced by the highest concentration of extract for the ST flies and by both concentrations of extract for the HB flies. The results suggest that M. velutina extract is not genotoxic but is antigenotoxic.