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1.
Basic Clin Pharmacol Toxicol ; 123(2): 207-212, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29575551

ABSTRACT

Garcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties. However, its safe use and other effects on the central nervous system require assessment. This study assessed the toxicological effects of GFC using the comet assay and the micronucleus test in mice treated for 28 days. A behavioural model was employed to detect possible injuries on the central nervous system. Mice treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to rotarod test, open-field test and tail suspension test (TST). After the behaviour tasks, biological samples were assessed to evaluate genotoxic and mutagenic effects using the comet assay and the micronucleus test. Garcinielliptone FC did not impair the performance of the animals in the rotarod and open-field tests, with no antidepressant-like effect in TST. No genotoxic effects in blood and cerebral cortex were observable in the comet assay; however, there was a significant increase in index and frequency of damage in liver after treatment with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was caused only by the highest dose, although no mutagenic potential was observed.


Subject(s)
Anticonvulsants/toxicity , Behavior, Animal/drug effects , Central Nervous System/drug effects , DNA Damage/drug effects , Triterpenes/toxicity , Animals , Anticonvulsants/isolation & purification , Clusiaceae/chemistry , Comet Assay , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Injections, Intraperitoneal , Liver/drug effects , Male , Mice , Micronucleus Tests , Models, Animal , Rotarod Performance Test , Toxicity Tests, Subacute , Treatment Outcome , Triterpenes/isolation & purification
2.
Article in English | MEDLINE | ID: mdl-27525021

ABSTRACT

Background. Industrial processing of the pecan nut Carya illinoinensis K. Koch generated a large amount of shells, which have been used to prepare nutritional supplements and medicinal products; however, the safe use of shells requires assessment. This study evaluated the toxic, genotoxic, and mutagenic effects of pecan shell aqueous extract (PSAE) and the possible contribution of phenolic compounds, ellagic and gallic acids, and inorganic elements present in PSAE to induce toxicity. Results. Levels of inorganic elements like K, P, Cl, and Rb quantified using the Particle-Induced X-Ray Emission method were higher in PSAE than in pecan shells, while Mg and Mn levels were higher in shells. Mice showed neurobehavioral toxicity when given high PSAE doses (200-2,000 mg kg(-1)). The LD50 was 1,166.3 mg kg(-1). However, PSAE (50-200 mg·kg(-1)) and the phenolic compounds (10-100 mg·kg(-1)) did not induce DNA damage or mutagenicity evaluated using the comet assay and micronucleus test. Treatment with ellagic acid (10-100 mg·kg(-1)) decreased triglyceride and glucose levels, while treatments with PSAE and gallic acid had no effect. Conclusion. Pecan shell toxicity might be associated with high concentrations of inorganic elements such as Mn, Al, Cu, and Fe acting on the central nervous system, besides phytochemical components, suggesting that the definition of the safe dose should take into account the consumption of micronutrients.

3.
Plant Foods Hum Nutr ; 70(4): 414-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26449221

ABSTRACT

Pecan shell decoction has been used to treat diabetes and obesity-related diseases. In this study, the effects of a pecan shell aqueous extract (PSAE) were evaluated in diabetic and hypercholesterolemic Wistar rats, analyzing clinical signs and biochemical as well as genotoxic and mutagenic parameters, to assess its safe use and efficacy. Diabetes mellitus and hypercholesterolemia were induced with streptozotocin (STZ) and tyloxapol, respectively. Animals were orally administered PSAE (100 mg/kg body weight, b.w.) for 28 days. Biochemical analyses and genotoxicity were evaluated in blood samples and mutagenicity was evaluated in bone marrow. PSAE treatment decreased the blood glucose level and stabilized clinical signs of diabetes in diabetic rats. PSAE diminished the increase in total cholesterol and triglyceride levels in hypercholesterolemic rats. The urea levels were higher in diabetic rats than in treated ones; however, creatinine values were the same in all groups. Elevated transaminase levels were suggestive of liver injuries in diabetic rats, and were not altered by PSAE treatment. PSAE did not show genotoxic or mutagenic activities in diabetic and hypercholesterolemic rats, indicating its safe use at 100 mg/kg b.w. not only in healthy rats but also in rats with induced metabolic alterations. The findings on PSAE's efficacy may indicate that its successful and popular use is in accordance with our results. Thus, PSAE might be a potential candidate for medical purposes as a complementary treatment of diabetes and hypercholesterolemia.


Subject(s)
Anticholesteremic Agents/therapeutic use , Carya/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Nuts/chemistry , Plant Extracts/therapeutic use , Animals , Blood Glucose/analysis , Cholesterol/blood , Diabetes Mellitus, Experimental/blood , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/chemically induced , Hypercholesterolemia/drug therapy , Male , Phytotherapy , Plant Extracts/adverse effects , Plant Extracts/chemistry , Polyethylene Glycols , Rats , Rats, Wistar , Triglycerides/blood , Urea/blood , Water
4.
J Ethnopharmacol ; 147(2): 474-80, 2013 May 20.
Article in English | MEDLINE | ID: mdl-23528362

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus articulatus (Apocynaceae) is a plant native to the Amazon, popularly used to treat external ulcers, tumors, inflammations, cancer, syphilis and malaria. AIM OF THE STUDY: To investigate the in vivo genotoxic and mutagenic potential of this plant, using the comet assay and the micronucleus test. MATERIAL AND METHODS: Female and male adult mice were treated with 500 mg/kg, 1000 mg/kg or 2000 mg/kg of Himatanthus articulatus aqueous or ethanolic bark extracts by gavage for two consecutive days. In addition, blood slides were exposed to hydrogen peroxide (ex vivo) to evaluate the anticlastogenic effect using the comet assay. The HPLC analyses indicated plumieride as the main constituent of both extracts from Himatanthus articulatus barks. RESULTS: No differences between genders were observed. Micronuclei were observed only in the group treated with the highest dose of both extracts. Conversely, lower doses of these extracts showed protective effects to DNA against damage induced by hydrogen peroxide, indicating an important antigenotoxic effect. CONCLUSIONS: The toxicological evaluation indicated that the extracts are non-genotoxic and reduce the clastogenic damage induced by hydrogen peroxide. In part, this result can be atributted to the phytochemical profile of Himatanthus articulatus, which presents iridoids and phenolic compounds.


Subject(s)
Apocynaceae , Plant Extracts/pharmacology , Animals , Bone Marrow/drug effects , Cells, Cultured , Comet Assay , Erythrocytes/drug effects , Ethanol/chemistry , Female , Flavonoids/analysis , Flavonoids/pharmacology , Furans/isolation & purification , Furans/pharmacology , Male , Medicine, Traditional , Mice , Micronucleus Tests , Phenols/analysis , Phenols/pharmacology , Plant Bark/chemistry , Plant Extracts/chemistry , Solvents/chemistry , South America , Spiro Compounds/isolation & purification , Spiro Compounds/pharmacology , Tannins/analysis , Tannins/pharmacology , Water/chemistry
5.
J Food Sci ; 78(2): T367-71, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23330610

ABSTRACT

UNLABELLED: The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic properties. However, few studies have assessed the possible toxic effects of artichoke extracts. This study evaluates genotoxic and mutagenic activities of artichoke leaf aqueous extract in mice using the comet assay and the micronucleus test. Leaf extracts were given by gavage (500 mg/kg, 1000 mg/kg, and 2000 mg/kg) for 3 consecutive days. Extract composition was investigated using phytochemical screening and high-performance liquid chromatography (HPLC). In addition, antioxidant capacity was analyzed through the diphenyl-picrylhydrazyl (DPPH) and xanthine oxidase assay. Phytochemical screening detected the presence of phenolic compounds, flavonoids, and saponins. HPLC analyses indicated the presence of chlorogenic acid, caffeic acid, isoquercetrin, and rutin. Extracts showed a dose-dependent free radical scavenging effect of DPPH and an inhibitory effect of xanthine oxidase. The genotoxic results showed that leaf extracts did not increase micronuclei in peripheral blood cells. Compared to the control group, a significant increase in comet assay values was observed only in bone marrow of group treated with 2000 mg/kg, the highest dose tested, indicating that artichoke tea should be consumed with moderation. PRACTICAL APPLICATION: This is the first report of in vivo mutagenic and genotoxic evaluation with C. scolymus. The present study revealed leaf aqueous extract from artichoke shows lack of mutagenicity in vivo, and low genotoxicity and antioxidant activity; indicating that artichoke tea should be consumed with moderation.


Subject(s)
Cynara scolymus/chemistry , DNA Damage/drug effects , Mutagens/pharmacology , Plant Extracts/pharmacology , Animals , Antioxidants/adverse effects , Chromatography, High Pressure Liquid , Comet Assay , Female , Flavonoids/analysis , Flavonoids/pharmacology , Male , Mice , Micronucleus Tests , Phenols/analysis , Phenols/pharmacology , Plant Leaves/chemistry , Saponins/analysis , Saponins/pharmacology , Xanthine Oxidase/analysis , Xanthine Oxidase/metabolism
6.
Basic Clin Pharmacol Toxicol ; 112(1): 34-41, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22788872

ABSTRACT

Platonia insignis Mart., a native species of the Brazilian Amazon more commonly known as bacuri, is a member of the Clusiaceae family. In this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from P. insignis seed ethanolic extract using different experimental models. Our results demonstrate in vitro antioxidant effects, by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1,1-diphenyl-2-picryl-hydrazyl assays, as well as in vivo effects in antioxidant-defective Saccharomyces cerevisiae strains to both fractions. Toxicity was evaluated against the micro-crustaceous Artemia salina Leach. and promastigote Leishmania amazonensis. The dichloromethane fraction was the most active fraction evaluated on A. salina and promastigote L. amazonensis (IC(50)  = 24.89 µg/mL and 2.84 µg/mL, respectively). In addition, a slight cytotoxicity was observed in mammalian V79 cells using ethyl acetate and dichloromethane fractions with MTT assays. Both fractions displayed genotoxicity up to 25 µg/mL (dichloromethane) and 10 µg/mL (ethyl acetate) in V79 cells, as evaluated by the alkaline comet assay. Thus, in this study, we demonstrate for the first time that ethyl acetate and dichloromethane fractions from P. insignis seeds display antioxidant effects, a toxic effect against A. salina and L. amazonensis and induce genotoxicity in V79 mammalian cells. The observed activities can be attributed to the phenolic compounds present in these fractions and to the presence of xanthones (alpha- and gamma-mangostin).


Subject(s)
Clusiaceae , Plant Extracts/pharmacology , Acetates , Animals , Antioxidants/pharmacology , Artemia/drug effects , Clusiaceae/chemistry , Cricetinae , Cricetulus , Leishmania/drug effects , Methylene Chloride , Phenols/analysis , Seeds
7.
Food Chem Toxicol ; 50(5): 1208-14, 2012 May.
Article in English | MEDLINE | ID: mdl-22306517

ABSTRACT

The aim of the present work was to study the protective effects of rosmarinic acid against ethanol-induced DNA damage in mice. The antigenotoxic capacity of rosmarinic acid (100 mg/kg) was tested using pre-, co- and post-treatment with ethanol (5 g/kg). Peripheral blood (1 and 24 h) and brain cells (24 h) were evaluated using the comet assay and bone marrow was analyzed using the micronucleus assay (24 h). The results were compared to data of TBARS, enzymes with antioxidant activity, and DCFH-DA test. Peripheral blood and brain cells show that mean damage index (DI) and damage frequency (DF) values of ethanol with pre-treatment with rosmarinic acid group were significantly lower than in the ethanol group. In brain cells all different treatments with ethanol and rosmarinic acid showed significant decrease in DI and DF mean values when compared to ethanol group and negative control. No significant differences were observed in micronucleus frequency, activity of antioxidant enzymes and TBARS between groups. The DCFH-DA test show a reduction of 18% of fluorescence intensity when compare with ethanol group. The results show that rosmarinic acid could decrease the levels of DNA damage induced by ethanol, for both tissues and treatment periods.


Subject(s)
Antimutagenic Agents/pharmacology , Cinnamates/pharmacology , Depsides/pharmacology , Ethanol/toxicity , Mutagens/toxicity , Animals , Comet Assay , Female , Male , Mice , Reactive Oxygen Species/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Rosmarinic Acid
8.
J Ethnopharmacol ; 125(1): 97-101, 2009 Aug 17.
Article in English | MEDLINE | ID: mdl-19539021

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) (Asteraceae) is a native plant from Brazil. Also known as "carqueja", it is popularly used to treat liver diseases, diabetes, as well as digestive disorders, mainly by women with lower socioeconomic status. AIM OF THE STUDY: The aim of the present study was to investigate the in vivo genotoxic/antigenotoxic and mutagenic potential of this plant, using the comet and the micronucleus assays. MATERIAL AND METHODS: Female adult mice were treated with 500, 1000 or 2000 mg/kg of B. trimera aqueous extract (Bt-AE) by gavage for three consecutive days. RESULTS: Independently of the dose, no genotoxic effect was observed in blood and liver samples analyzed by the comet assay. Conversely, B. trimera showed an antigenotoxic effect in blood from treated mice, thus protecting cells against oxidative DNA damage induced by the ex vivo treatment with hydrogen peroxide. In addition, Bt-AE showed in vitro antioxidant activity, assessed by DPPH and xanthine oxidase assays, suggesting that the observed antigenotoxic effects might be related to its antioxidant properties. CONCLUSIONS: However, the extract increased the frequency of micronucleus in bone marrow of treated mice, indicating a chromosomal mutagenic activity. Thus, medicines prepared from this plant should be used with caution, although the results also suggest antigenotoxic effects for B. trimera aqueous extract.


Subject(s)
Antimutagenic Agents/pharmacology , Baccharis/chemistry , Mutagens/pharmacology , Plant Extracts/pharmacology , Animals , Comet Assay , DNA Damage , Dose-Response Relationship, Drug , Female , Mice , Micronucleus Tests , Oxidative Stress , Xanthine Oxidase/metabolism
9.
J Ethnopharmacol ; 124(2): 321-4, 2009 Jul 15.
Article in English | MEDLINE | ID: mdl-19397982

ABSTRACT

Baccharis dracunculifolia (D.C.) (Asteraceae), a native plant to Brazil known as "vassourinha" or "alecrim-do-campo", is the most important botanical source of a Brazilian propolis called green propolis. The leaf extracts of this plant have been used to treat liver and digestive disorders. It has been recognized that green propolis can induce mutagenic effects at high doses, but no study reporting possible mutagenic effects by Baccharis dracunculifolia extracts in the maximum tolerated dose has been conducted. The aim of the present study was to investigate the genotoxic and mutagenic effects of this plant in vivo. Adult CF-1 mice were treated with 0.5g/kg, 1.0g/kg or 2.0g/kg of an aqueous extract of Baccharis dracunculifolia by gavage for 3 consecutive days. Blood and liver samples were collected to detect DNA damage using the comet assay, while bone marrow samples were used to assess chromosome mutations by the micronucleus test. The extract increased the DNA damage in blood and liver tissues and the frequency of micronucleus in bone marrow. These findings suggest genotoxic and mutagenic effects of Baccharis dracunculifolia comparable to green propolis in mice.


Subject(s)
Baccharis , Bone Marrow/drug effects , DNA Damage , Mutagenesis/drug effects , Mutagens/toxicity , Plant Extracts/toxicity , Animals , Blood/drug effects , Chromosomes/drug effects , Female , Liver/drug effects , Mice , Micronucleus Tests , Plant Components, Aerial , Propolis/toxicity
10.
J Nat Prod ; 68(5): 784-6, 2005 May.
Article in English | MEDLINE | ID: mdl-15921431

ABSTRACT

Two new benzophenones were isolated from the leaves of Hypericum carinatum. Their structures were established on the basis of 2D NMR spectroscopic analyses and mass spectrometry as cariphenone A (6-benzoyl-5,7-dihydroxy-2,2,8-trimethyl-2H-chromene) (1) and cariphenone B (8-benzoyl-5,7-dihydroxy-2,2,6-trimethyl-2H-chromene) (2). Five known compounds, the phloroglucinol derivative uliginosin B (3), 1-eicosanol, sitosterol, stigmasterol, and campesterol, were also characterized. Compounds 1-3 were evaluated for their total antioxidant capacity through a total radical-trapping parameter assay. Only compound 1 showed moderate antioxidant activity, exhibiting inhibition of chemiluminescence similar to that of quercetin at the same concentration.


Subject(s)
Antioxidants/isolation & purification , Benzophenones/isolation & purification , Hypericum/chemistry , Plants, Medicinal/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Benzophenones/chemistry , Benzophenones/pharmacology , Brazil , Dose-Response Relationship, Drug , Luminescent Measurements , Molecular Structure , Phloroglucinol/analogs & derivatives , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Plant Leaves/chemistry , Quercetin/pharmacology
11.
Fitoterapia ; 76(2): 210-5, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15752632

ABSTRACT

In the present study we have investigated the in vitro antitumor effects of three benzopyrans, 6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran (1), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethylbenzopyran (2) and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethylbenzopyran (3) isolated from Hypericum polyanthemum. The three compounds tested demonstrated potent growth inhibitory activity at 40 microg/ml (<25% control growth) in the NCI-H460, HT-29 and U-373MG human cell lines. Determination of cell cycle distribution demonstrated that the antiproliferative effect of the three benzopyrans could be associated to alterations in the cell cycle phase distribution. Treatment with the IC50 of the three compounds induced an arrested in S phase. Only in cells treated with compound 3 did the percentage of sub-G1 population increase up to 9%, suggesting that this compound induced more cell death than the others. Consistent with sub-G1 analysis, appreciable oligonucleosomal DNA fragmentation was only observed in the NCI-H460 cell line treated with compound 3. From these results it can be suggested that despite no differences among the cytotoxicity of the three compounds, it was observed that the mechanism of their antiproliferative effects appears to be different.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Cycle/drug effects , Hypericum , Phytotherapy , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Benzopyrans/administration & dosage , Benzopyrans/pharmacology , Benzopyrans/therapeutic use , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , DNA Fragmentation/drug effects , Flow Cytometry , Humans , Inhibitory Concentration 50 , Plant Components, Aerial , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use
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