Flavonoids composition, antioxidant, anticholinesterase, and cytotoxic activities of flowers extract of Senna cearensis Afr. Fern.

The Senna genus has a wide diversity of species, with an interesting chemical composition of secondary metabolites and applications as medicine. The folk medicine, mainly in developing countries, uses species of Senna to treat seizures, epilepsy and constipation. Though the recognized bioactivity, some Brazilian native species of Senna remain unexplored, such as Senna cearensis, a native species of Caatinga. This is the first report about the bioactivity of the flowers of S. cearensis Afr. Fern., a native species of northeast Brazil. In this communication, flavonoids and catechins are identified in S. cearensis flowers and the chemical composition is linked with its antioxidant, anticholinesterase, and cytotoxic activities. By UPLC-QTOF, some compounds that belong to the class of flavonoids were identified. They are: catechin, epigallocatechin, guibourtinidol-(4α-8)-catechin, and cassiaflavan-(Cat)-epicatechin. The cytotoxic activity is more noticeable for the HL60 (leukemia) cell line with a cell growth inhibition (GI%) of 81.65 ± 5.65.

Virtual screening of flavonoids from Chamaecrista genus: ADME and pharmacokinetic properties, interactions of flavonoid-DNA complex by molecular docking and molecular dynamics.

This research aimed to conduct an in silico study of compounds, mainly flavonoids, that are found in several plants, including the species of the Chamaecrista genus. The ADME properties, the drug-likeness score and properties of Lipinski and Veber rules of the molecules were determined using online databases. Based on the predicted properties, four flavonoids, apigenin, fisetin, luteolin and ononin were selected for molecular docking and dynamic simulations to study their interactions with DNA (PDB ID: 1BNA). The molecular docking showed that ononin has a high affinity for B-DNA, exhibiting a ΔG value of -9.3 kcal mol-1, compared with the other flavonoids. The molecular dynamic simulations of the flavonoid-DNA complexes showed that the flavonoids interacted with DNA by hydrogen bonding, hydrophobic interaction and π-stacking. The flavonoid ononin showed the best interaction energy value of -291.3490 kJ mol-1, compared with the other flavonoids.Communicated by Ramaswamy H. Sarma.

Hyperphagia and hyperleptinemia induced by low-protein, high-carbohydrate diet is reversed at a later stage of development in rats.

This study investigated whether increased food intake after 15 days of low-protein, high-carbohydrate (LPHC) and its normalization in the later period of development change the content of key proteins related to leptin or adiponectin signaling in the hypothalamus. Male rats were divided into five groups: Control groups received a control diet (17% protein, 63% carbohydrate) for 15 (C15) or 45 (C45) days; LPHC groups received an LPHC diet (6% protein, 74% carbohydrate) for 15 (LPHC15) or 45 (LPHC45) days; and Reverse group (R): received LPHC diet for 15 days followed by control diet for another 30 days. The LPHC15 group showed increased adiposity index, leptin level, and adiponectin level, as well as decreased the leptin receptor (ObRb) and pro-opiomelanocortin (POMC) content in the hypothalamus compared with the C15 group. LPHC diet for 45 days or diet reversion (R group) rescued these alterations, except the adiponectin level in LPHC45 rats, which was higher. In summary, LPHC diet reduced hypothalamic leptin action by diminishing ObRb and POMC levels, leading to hyperphagia and adiposity body. Medium-term administration of LPHC diet or reverting to control diet restored the levels of these proteins, thereby improving body lipid mass rearrangement in adulthood.

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

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-ß-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.

Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae).

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30 µM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H(2)O(2) in the HepG2 cell line in concentrations above 0.04 µM with post-treatment, and above 0.08 µM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H(2)O(2). In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant.

Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31 percent), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53 percent). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.