Margaritaria nobilis L.F. (Phyllanthaceae): Ethnopharmacology and Application of Computational Tools in the Annotation of Bioactive Molecules.

Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O-glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids (10, 14, 15, 21, 24-26, 28-30, 33-35, 40 and 41) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group (6, 19, 22, 31, 38 and 43), one presents the DHHDP group (5), and four contain oxidatively modified congeners (12, 20, 37 and 39). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities.

Low doses of methylmercury intoxication solely or associated to ethanol binge drinking induce psychiatric-like disorders in adolescent female rats.

Methylmercury (MeHg) is an environmental contaminant that provokes damage to developing brain. Simultaneously, the consumption of ethanol among adolescents has increased. Evidence concerning the effects of MeHg low doses per se or associated with ethanol during adolescence are scarce. Thus, we investigate behavioral disorders resulted from exposure to MeHg low doses and co-intoxicated with ethanol in adolescent rats. Wistar rats received chronic exposure to low doses of MeHg (40 µg/kg/day for 5 weeks) and/or ethanol binge drinking (3 g/kg/day at 3 days per week for 5 weeks). Animals were submitted to behavioral assays to assess emotionality and cognitive function. Total mercury content was evaluated in the brain and hair. Oxidative parameters were analyzed in blood samples. MeHg at low doses or associated to ethanol binge drinking produced psychiatric-like disorders and cognitive impairment. Peripherally, MeHg altered oxidative parameters when associated to ethanol. Ethanol administration reduced brain mercury deposit. We proposed that ethanol reduces the necessity of mercury tissue levels to display psychiatric-like disorders/cognitive impairment.

Unravelling motor behaviour hallmarks in intoxicated adolescents: methylmercury subtoxic-dose exposure and binge ethanol intake paradigm in rats.

Methylmercury (MeHg) is a hazardous environmental pollutant, affecting Amazon basin communities by anthropogenic activities. The exact safe level of MeHg exposure is unclear, despite the efforts of health international societies to avoid mercury (Hg) poisoning. Central nervous system is severely impacted by Hg intoxication, reflecting on motor impairment. In addition, alcohol has been associated to an overall brain damage. According to lifestyle of Amazon riverside communities, alcohol intake occurs frequently. Thus, we investigated if continuous MeHg exposure at low doses during adolescence displays motor deficits (experiment 1). In the experiment 2, we examine if the co-intoxication (i.e. MeHg plus ethanol exposure) during adolescence intensify motor damage. In the experiment 1, Wistar adolescent rats (31 days old) received chronic exposure to low dose (CELD) of MeHg (40 µg/kg/day) for 35 days. For the experiment 2, five sessions of alcohol binge drinking paradigm (3ON-4OFF; 3.0 g/kg/day) were employed associated to MeHg intoxication. Motor behaviour was evaluated by the open field, pole test, beam walking and rotarod paradigms. CELDS of MeHg display motor function damage, related to hypoactivity, bradykinesia-like behaviour, coordination deficits and motor learning impairment. Co-intoxication of MeHg plus ethanol reduced cerebellar Hg content, however also resulted in motor behavioural impairment, as well as additive effects on bradykinesia and fine motor evaluation.

Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies.

Cardiovascular diseases (CVD) are an important cause of death worldwide. Anthocyanins are a subgroup of flavonoids found in berries, flowers, fruits and leaves. In epidemiological and clinical studies, these polyphenols have been associated with improved cardiovascular risk profiles as well as decreased comorbidities. Human intervention studies using berries, vegetables, parts of plants and cereals (either fresh or as juice) or purified anthocyanin-rich extracts have demonstrated significant improvements in low density lipoproteins oxidation, lipid peroxidation, total plasma antioxidant capacity, and dyslipidemia as well as reduced levels of CVD molecular biomarkers. This review discusses the use of anthocyanins in animal models and their applications in human medicine, as dietary supplements or as new potent drugs against cardiovascular disease.