Flávia Aparecida Resende

Bio: Flávia Aparecida Resende is an academic researcher from Sao Paulo State University. The author has contributed to research in topics: Ames test & Genotoxicity. The author has an hindex of 17, co-authored 42 publications receiving 886 citations.

Mutagenicity of flavonoids assayed by bacterial reverse mutation (Ames) test.

Abstract: The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. In the Ames assay, quercetin acted directly and its mutagenicity increased with metabolic activation. In the presence of S9 mix, kaempferol and galangin were mutagenic in the TA98 strain and kaempferol showed signs of mutagenicity in the other strains. The absence of hydroxyl groups, as in flavone, only signs of mutagenicity were shown in strain TA102, after metabolization and, among monohydroxylated flavones (3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone), the presence of hydroxyl groups only resulted in minor changes. Luteolin and fisetin also showed signs of mutagenicity in strain TA102. Finally, chrysin, which has only two hydroxy groups, at the 5-OH and 7-OH positions, also did not induce mutagenic activity in any of the bacterial strains used, under either activation condition. All the flavonoids were tested at concentrations varying from 2.6 to 30.7 nmol/plate for galangin and 12.1 to 225.0 nmol/plate for other flavonoids. In light of the above, it is necessary to clarify the conditions and the mechanisms that mediate the biological effects of flavonoids before treating them as therapeutical agents, since some compounds can be biotransformed into more genotoxic products; as is the case for galangin, kaempferol and quercetin.

Characterization and Quantification of the Compounds of the Ethanolic Extract from Caesalpinia ferrea Stem Bark and Evaluation of Their Mutagenic Activity

Abstract: Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This present work aims to assess the qualitative and quantitative profiles of the ethanolic extract from the stem bark of C. ferrea and to evaluate its mutagenic activity, using a Salmonella/microsome assay for this species. As a result, a total of twenty compounds were identified by Flow Injection Analysis Electrospray Ionization Ion Trap Mass Spectrometry (FIA-ESI-IT-MS/MSn) in the ethanolic extract from the stem bark of C. ferrea. Hydrolyzable tannins predominated, principally gallic acid derivatives. The HPLC-DAD method was developed for rapid quantification of six gallic acid compounds and ellagic acid derivatives. C. ferrea is widely used in Brazil, and the absence of any mutagenic effect in the Salmonella/microsome assay is important for pharmacological purposes and the safe use of this plant.

Evaluation of estrogenic potential of flavonoids using a recombinant yeast strain and MCF7/BUS cell proliferation assay.

Abstract: Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. Furthermore, there is a search for compounds with estrogenic activity that can replace estrogen in hormone replacement therapy during menopause, without the undesirable effects of estrogen, such as the elevation of breast cancer occurrence. Thus, the principal objective of this study was to assess the estrogenic activity of flavonoids with different hydroxylation patterns: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone via two different in vitro assays, the recombinant yeast assay (RYA) and the MCF-7 proliferation assay (E-screen), since the most potent phytoestrogens are members of the flavonoid family. In these assays, kaempferol was the only compound that showed ERα-dependent transcriptional activation activity by RYA, showing 6.74±1.7 nM EEQ, besides acting as a full agonist for the stimulation of proliferation of MCF-7/BUS cells. The other compounds did not show detectable levels of interaction with ER under the conditions used in the RYA. However, in the E-screen assay, compounds such as galangin, luteolin and fisetin also stimulated the proliferation of MCF-7/BUS cells, acting as partial agonists. In the evaluation of antiestrogenicity, the compounds quercetin, chrysin and 3-hydroxyflavone significantly inhibited the cell proliferation induced by 17-β-estradiol in the E-screen assay, indicating that these compounds may act as estrogen receptor antagonists. Overall, it became clear in the assay results that the estrogenic activity of flavonoids was affected by small structural differences such as the number of hydroxyl groups, especially those on the B ring of the flavonoid.

Protective effect of rosmarinic acid on V79 cells evaluated by the micronucleus and comet assays.

Abstract: Rosmarinic acid (RA) is a naturally occurring phenolic compound, which contributes to the beneficial and health-promoting effects of herbs, spices and medicinal plants. RA has shown several biological activities, such as hepatoprotective, anti-inflammatory, antiangiogenic, antitumor, antidepressant, antineurodegenerative, HIV-1 inhibitory and antioxidant effects. The aim of this study was to investigate the ability of RA to prevent chemically induced chromosome breakage or loss and primary DNA damage using the micronucleus and comet assays with V79 cells, respectively. The chemotherapeutic agent doxorubicin (DXR; 0.5 microg ml(-1)) was used as the DNA-damaging agent. The cultures were treated with different concentrations of RA (0.28, 0.56 and 1.12 mm) alone or in combination with DXR. The results showed that RA exerted no genotoxic effect, but significantly reduced the frequency of micronuclei and the extent of DNA damage induced by DXR at the three concentrations tested. The antioxidant activity of RA might be involved in the reduction of DXR-induced DNA damage observed in the present study.

Antitumour metal compounds: more than theme and variations

Abstract: Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

Recent advances in the chemical composition of propolis.

Abstract: Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species.

The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review

Abstract: Background Quercetin, one of the most well-known flavonoids, has been included in human diet for a long history. The use of quercetin has been widely associated with a great number of health benefits, including antioxidant, anti-inflammatory, antiviral and anticancer as well as the function to ease some cardiovascular diseases (i.e., heart disease, hypertension, and high blood cholesterol). However, poor water solubility, chemical instability and low bioavailability of quercetin greatly limit its applications. Utilization of delivery systems can improve its stability, efficacy and bioavailability. Scope and approach In this review, biological activities, chemical stability, metabolism and toxicity of quercetin and different delivery systems for quercetin were discussed. Key findings and conclusions Quercetin digested in human body (e.g., mouth, small intestine, liver, kidneys) undergoes glucuronidation, sulfation or methylation. During the food processing and storage, many factors such as heat, pH, metal ions, could affect the chemical stability (including oxidation and degradation) of quercetin. Utilization of delivery systems including lipid-based carriers, nanoparticles, inclusion complexes, micelles and conjugates-based encapsulation has the potential to improve both the stability and bioavailability and thus health benefits of quercetin. Each delivery system has its unique advantages and shortcomings, and the specific selection should be based on the application domains. Moreover, the exploration of natural food-grade ingredients as main compositions of delivery systems for quercetin might be required in the future.