Preclinical safety evaluation of the ethanolic extract from the aerial parts of Gomphrena celosioides Mart. in rodents.

The toxicological potential of the ethanolic extract from Gomphrena celosioides (EEGC), a medicinal plant used as a natural analgesic, was investigated in acute and subacute toxicity models in rodents. For the acute toxicity test, 2000 mg/kg of EEGC was administered orally to male and female Wistar rats, while Swiss mice received 75, 150 or 300 mg/kg of EEGC for the subacute toxicity test. Animals treated with an only dose of 2000 mg/kg EEGC showed no clinical signs of toxicity, indicating that the LD50 is higher than this dose. The repeated treatment with EEGC did not cause adverse clinical signs, or lesions in target tissues. According to the Globally Harmonized System of classification, the EEGC dosages can be in Category 5 which is the least toxic or non-toxic one.

Toxicological evaluation of ethanolic extract of leaves from Doliocarpus dentatus in Swiss mice.

Doliocarpus dentatus (Dilleniaceae) has been used in folk medicine to treat inflammation and pain; however, studies evaluating its toxicity potential, as well as its effects on anxiety and depression, are scarce. This study investigated the toxicological profile of an ethanolic extract from leaves of D. dentatus (EEDd), and its effects on anxiety and depression models in mice. Male and female mice received either a single dose (500, 1000 or 2000 mg/kg) or repeated doses (75, 150 or 300 mg/kg) of EEDd by oral gavage. During the subacute toxicity assay, behavioral tests were performed on days 4, 14, 21 and 28. No evidence of toxicity was observed in the animals in both acute and subacute tests. However, males treated with the highest dose presented a reduction in the absolute weight of the kidney, an elevation in the AST levels, in addition to an alteration in the urea levels. The treatment did not affect other biochemical parameters, and did not induce any depressive-like behavior. EEDd exhibited low toxicity after single and repeated exposures. Since some analyzed parameters were compromised, further toxicity studies should be carried out.

Preclinical safety evaluation of the aqueous extract from Mangifera indica Linn. (Anacardiaceae): genotoxic, clastogenic and cytotoxic assessment in experimental models of genotoxicity in rats to predict potential human risks.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants widely used by the population contain significant concentrations of biologically active compounds and, although they have proven pharmacological properties, can cause DNA damage and develop fatal diseases. AIM OF THE STUDY: The present study aimed to evaluate the genotoxic, cytotoxic potential and clastogenic effects of the aqueous extract from Mangifera indica leaves (EAMI) on rats submitted to experimental genotoxicity models and through the SMART test performed in Drosophila melanogaster. MATERIAL AND METHODS: The comet assay and the micronucleus test were performed on peripheral and bone marrow blood, respectively, of Wistar rats, orally treated with EAMI at doses of 125, 250, 500 and 1000 mg/kg/bw for 28 days. In the SMART test, the standard cross between three mutant D. melanogaster strains was used. Larvae were treated with EAMI at different concentrations, and the wings of adult flies were evaluated for the presence/frequency of mutant spots and compared to the negative control group. RESULTS: Phytochemical analysis of EAMI indicated high levels of flavonoids. The tests performed in rats showed that EAMI did not present significant genotoxic or clastogenic effects. The results showed a critical dose-dependent cytoprotective effect exerted by EAMI. This result was attributed to the high content of polyphenols and flavonoids. The biotransformation metabolites of EAMI did not present genotoxic activity, as demonstrated by the SMART test. CONCLUSIONS: These results are relevant since they provide safety information about a plant species of great therapeutic, economical, nutritious and ethnopharmacological value for the population.

Mechanisms underlying antiatherosclerotic properties of an enriched fraction obtained from Ilex paraguariensis A. St.-Hil.

BACKGROUND: Ilex paraguariensis A. St. Hil. var. paraguariensis (Aquifoliaceae) popularly known as 'mate' is an important species native to South America. Despite numerous studies showing significant antioxidant and lipid lowering properties, the antiatherosclerotic mechanisms of this species remain unknown. PURPOSE: To evaluate the possible antiatherosclerotic effects of a butanolic fraction (n-BFIP) obtained from I. paraguariensis and to investigate the molecular mechanisms involved in this activity. METHODS: First, n-BFIP was obtained from the hydroalcoholic extract and a detailed phytochemical investigation about its main secondary metabolites was performed. Then, during 8 experimental weeks, rabbits received diet supplemented with 1% cholesterol (CRD). After 4 weeks of CDR, animals were redistributed into five groups (n = 6) and treated (p.o.) with n-BFIP (10, 30 and 100 mg/kg), simvastatin (5 mg/kg), or vehicle (filtered water, 1 ml/kg) once daily for 4 weeks. An additional group was fed with cholesterol-free diet and treated with vehicle. At the end of 8 weeks, serum samples were obtained for the measurement of serum lipids, lipid and protein oxidation and indirect nitric oxide levels. In addition, serum IL-1ß, IL-6, sICAM-1, sVCAM-1, and intracellular cGMP levels in rabbit aortic rings were measured. Samples from the aortic arch and thoracic segment were collected for histopathological analysis. RESULTS: CRD induced oxidative and nitrosative stress and increased serum lipids, IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels. In addition, structural changes in the intima layers of different arterial branches were also found. Although it did not change serum lipids, n-BFIP reverted oxidative and nitrosative stress and reduced IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels, besides to increasing intracellular levels of cGMP in vitro. In addition, the formation of atherosclerotic plaques was reduced to values close to those of animals fed with cholesterol-free diet. CONCLUSIONS: A 4-week n-FBIP treatment reduces the progression of the atherosclerotic disease in New Zealand rabbits. These effects are associated with an attenuation of oxidative and nitrosative stress, affecting IL-1ß, IL-6, sICAM-1 and sVCAM-1 levels.