Assessment of the DNA damaging potency and chemopreventive effects towards BaP-induced genotoxicity in human derived cells by Monimiastrum globosum, an endemic Mauritian plant.

Naturally occurring compounds have protective effects towards mutagens and carcinogens. The leaf extract of Monimiastrum globosum (Bois de Clous), a Mauritian endemic plant from the Myrtaceae family, was studied for its potency to induce DNA damage in human HepG2 hepatoma cells using DNA migration as a biological endpoint in the alkaline single cell gel electrophoresis (SCGE) assay. This was contrasted with the ability to modulate the benzo[a]pyrene (BaP)-dependent DNA damage in human hepatoma cells. M. globosum caused genotoxicity in HepG2 cells at concentrations exceeding 3mg fresh weight (FW) per ml cell culture in the absence of cytotoxicity. Pre-treatment of the cells with 12.2 microg FW/ml to 1.56 mg FW/ml led to a pronounced antigenotoxic effect towards BaP-induced DNA damage. DNA migration (OTM) was reduced by 66%, 81.5% and 74% for 49, 98 and 195 microg FW/ml, respectively. A U-shaped dose-response curve was derived for M. globosum indicating genotoxic effects in high doses and antigenotoxic effects in low doses. M. globosum extract had total phenolics (15 mg/g FW) with flavonoids (aglycones and conjugates: 8 mg/g FW) and proanthocyanidins (3mg/g FW) as major phenolic subclasses. The hydrolysis of conjugated flavonoids yielded the aglycones quercetin (606 microg/g FW) and kaempferol (117.8 microg/g FW) while HPLC-MS/MS analysis of the total extract revealed free flavonoids such as quercetin (19.2 microg/g FW) and myricetin (2.5 microg/g FW). The antioxidant activity of the extract of M. globosum, assessed by the FRAP and TEAC assays yielded values of 275+/-3.82 micromol/g FW and 346+/-4.2 micromol/g FW, respectively.

Extract of Toxicodendron quercifolium caused genotoxicity and antigenotoxicity in bone marrow cells of CD1 mice.

As has been shown in numerous studies, naturally occurring compounds can have protective effects towards mutagens and carcinogens. In the present study, the genotoxic/antigenotoxic effect of Toxicodendron quercifolium (poison ivy) extract, which has been identified as antigenotoxic in human HepG2 cells in former studies, was examined in the in vivo micronucleus assay using polychromatic erythrocytes (PCE) of bone marrow of CD1-mice. For this, D0 (1:10), D0 (1:25), D0 (1:50), D1 (1:50), D2 (1:50), and D4 (1:50) dilutions of ethanolic plant extract prepared on the basis of the "Hömoopathisches Arzneimittelbuch (HAB 2000)" were administered orally to CD1 mice over a period of two days. A significant increase (p < 0.05) in micronucleus frequencies was found after administration of D0 (1:10), the highest tolerated dose. Additionally, antigenotoxic effects of T. quercifolium towards benzo(a)pyrene-induced micronucleus formation were studied. For that, four dilutions of the plant extract [D0, D2, D4, D6, each 1:50] were administered orally to CD1 mice for five days prior to the administration of benzo(a)pyrene (250 mg/kg b.w.) for another two days. It was found that the administration of the dilutions D0 (1:50) and D2 (1:50) of T. quercifolium extract significantly inhibited benzo(a)pyrene-induced micronucleus formation (p < 0.0001). The results of this study indicated that T. quercifolium extract has the character of a so-called "Janus"-genotoxin: High doses led to a weak but significant increase of micronucleus frequencies whereas low doses showed chemopreventive effects towards benzo(a)pyrene-induced DNA damage. The constituents of T. quercifolium responsible for the genotoxic and antigenotoxic effects may be flavonoids, which are known to have prooxidative and scavenging effects and identified by HPLC-MS/MS.