Effect of Adding Matricaria recutita L., Cymbopogon citratus, or Mentha piperita L. Extracts to Fermented Orange Beverage: Sensory Evaluation, Physicochemical Characterization, and Prediction of Toxic Risks and Biological Activity In Silico.

Fermentation is an important tool in producing functional beverages through agro-industrial wastes, and medicinal and aromatic plants due to the specific content of bioactive molecules. Therefore, this study evaluated the contribution of Matricaria recutita (chamomile), Cymbopogon citratus (lemongrass), or Mentha piperita (peppermint) extracts to the phytochemical profile and potential biological effects of a functional fermented orange beverage in vitro and in silico. The concentrations of aromatic herbal extracts that yielded the best sensory performance for fermented beverages were selected for analyses that involved characterizing the fermented beverages. The beverages that received the extracts (2%) had the highest phenolic and flavonoid content and antioxidant potential compared to the control. Hesperidin (124-130 mg L-1), narirutin (66-70 mg L-1), chlorogenic (11-16 mg L-1), caffeic (5.3-5.5 mg L-1), and ferulic (1-1.7 mg L-1) acids were found in the different formulations. The in silico analysis suggested that the evaluated compounds do not present a toxicity risk (mutagenicity, carcinogenicity, hepatotoxicity, and ability to penetrate the blood-brain barrier). Additionally, they can contribute to the biological effects of therapeutic importance, such as antioxidant, gastroprotective, and anti-ulcerative properties, and the Mentha piperita L. extract presented the greatest potential among the evaluated herbs for use in functional fermented beverages.

Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition.

The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.

In silico and in vivo protective effect of Morus nigra leaves on oxidative damage induced by iron overload.

Morus nigra L. is a plant popularly known as 'amoreira preta', very used in folk medicine. Iron overload (hemochromatosis) is a clinical condition that causes damage to various tissues due to oxidative stress. Therapy to control iron overload is still unsatisfactory. The protective effect on oxidative stress induced by iron overload was verified. Phytochemical characterization was evaluated by UHPLC-MS/MS. The in silico toxicity predictions of the main phytochemicals were performed via computer simulation. To induce iron overload, the animals received iron dextran (50 mg/kg/day). The test groups received doses of 500 and 1000 mg/kg of M. nigra extract for six weeks. Body weight, organosomatic index, serum iron, hepatic markers, cytokines, interfering factors in iron metabolism, enzymatic and histopathological evaluations were analyzed. Vanillic acid, caffeic acid, 6-hydroxycoumarin, p-coumaric acid, ferulic acid, rutin, quercitrin, resveratrol, apigenin and kaempferol were identified in the extract. In addition, in silico toxic predictions showed that the main compounds presented a low probability of toxic risk. The extract of M. nigra showed to control the mediators of inflammation and to reduce iron overload in several tissues. Our findings illustrate a novel therapeutic action of M. nigra leaves on hemochromatosis caused by iron overload.

Acute toxicity and antimicrobial activity of leaf tincture Baccharis trimera (Less).

BACKGROUND: The present study aimed to evaluate the possible acute oral toxicity of Baccharistrimera leaf dye as well as its antimicrobial activity. METHOD: Organization for Economic co-operation and development (OECD) 423 was used to assess acute oral toxicity and as per protocol a dose of 2000 mg/kg of tincture was administered to Wistar rats, male and female, and observed for 14 days. Biochemical and hematological analyzes were performed with sample collected of rat. The dye was evaluated for antimicrobial activity by agar diffusion and microdilution methods, which allow to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and antibiofilm potential. RESULTS: The results showed that there was no loss of animals and no significant changes in hematological and biochemical parameters after oral administration of 2000 mg/kg of tincture and was considered safe by the OECD, classified as category 5. The dyeing also showed an important antimicrobial activity against gram positive and gram negative bacteria also significantly decreased the microbial biofilm. CONCLUSION: The tincture of B.trimera leaf when given orally once can be considered safe and has a relevant antimicrobial potential that should be elucidated in subsequent research.

Safety assessment of Morus nigra L. leaves: Acute and subacute oral toxicity studies in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus nigra L. is a plant native to Asia, and well adapted to the Brazilian climate. It is popularly known as "amoreira preta", and is part of the National List of Plants of Interest to the Brazilian Unified Health System. It is used in folk medicine mainly to soften the effects of menopause, as anti-inflammatory, antidiabetic and antihypertensive. However, information on safe doses and use is still precarious. AIM OF THE STUDY: To identify the chemical composition of the ethanolic extract of Morus nigra L. leaves (EEMN), as well as perform a toxicological study in male and female rats. MATERIALS AND METHODS: The chemical composition of the extract was performed by HPLC/DAD. In the acute study, the dose administered was 2000 mg/kg, and signs of toxicity and mortality was observed. In the sub-acute study, the extract was administered at doses of 500, 750 and 1000 mg/kg for 28 days. Behavioral changes, object recognition test, renal and hepatic tissue assessments, biochemical and hematological parameters were determined. The extract was administered orally to male and female rats in both studies. RESULTS: Quercetin and caffeic acid showed as major compounds in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the protocol. In the subacute study, there was a decrease in AST in males (750 and 1000 mg/kg) and females (1000 mg/kg), reduction of total cholesterol in females (750 and 1000 mg/kg), and increase in renal and hepatic change the LPO levels. CONCLUSION: The present investigation showed that EEMN did not present significant toxic effects when administered orally. Moreover, presented a potentially protective action of organs and possesses hypocholesterolemic activity, thus, it is shown as a promising natural source to be used in pharmacology.

Safety assessment of ethanolic extract of Olea europaea L. leaves after acute and subacute administration to Wistar rats.

Olea europaea L., popularly known as olive, is a plant widely used worldwide. Its leaves, fruit and oil are extensively consumed and present important pharmacological properties. However, studies regarding the toxicity of olive leaves are still limited in the literature. Therefore, the aim of the study was to investigate acute and subacute oral toxicities of the ethanolic extract of olive leaves (EEO) in Wistar rats through histopathology and biochemical and hematological parameters. Acute toxicity was assessed using a single dose of 2000 mg/kg of EEO administered by oral gavage to male and female rats. To assess subacute toxicity, EEO was administered during 28 days at different doses (100, 200 and 400 mg/kg) to male and female rats. At the end of the experiments, the liver and kidney were removed and examined microscopically, and blood was collected for hematological and biochemical parameters. A single dose of 2000 mg/kg did not induce mortality or any signs of toxicity among the animals treated. Animals exposed to EEO during 28 days did not present sign of abnormalities. Results demonstrated that EEO did not induce toxicity after exposure to single and repeated doses. However, more studies are needed to fully understand implications for human safety.