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1.
J Ethnopharmacol ; 138(2): 513-22, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-22015234

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less) DC. (Asteraceae), popularly known in Brazil as "carqueja", have been used in folk medicine to treat gastrointestinal, hepatic and renal diseases, and inflammatory processes as rheumatism. AIM OF THE STUDY: To evaluate the in vitro and in vivo toxicological effects of anti-inflammatory Baccharis trimera aqueous extract and fractions. MATERIALS AND METHODS: Aqueous extract of Baccharis trimera (AEBt) was produced by infusion in boiling water. After lyophylization AEBt was extracted with 80% ethanol, originating the ethanolic supernatant fraction (EFBt) and the aqueous sediment fraction (AFBt). Anti-inflammatory properties of AEBt, EFBt or AFBt (3, 30 or 300 µg/kg b.w.) were evaluated by the carrageenan-induced mouse paw edema using indomethacin (10mg/kg) as positive control. The growth of rat hepatoma cells (HTC) and human embryo kidney epithelial cells (HEK) was determined by protein staining assay. Cytotoxicity was assayed by the tetrazolium salt (MTT) reduction. Cyclosporin was used as reference cytotoxic drug for spleen cells and doxorubicin for HTC and HEK cells. For in vivo toxicological evaluation SW male mice were daily and oral (gavage) treated with extract/fractions at 4.2mg/kg or 42 mg/kg during 15 days. After treatment liver or kidney cells were submitted to comet assay to determine the DNA damage index, and the glutathione S-transferase activity was assayed towards ETHA (class Pi) and CDNB (several classes). Mutagenicity was evaluated by the Ames test using Salmonella typhimurium strains TA97, TA98, TA100, and TA102. RESULTS: The anti-inflammatory effects of EFBt were higher than those of AEBt or AFBt. Mice treatment (3-300 µg/kg) with AFBt reduced the paw edema (3h) at lower levels (29.2-37.3%; P<0.01), than those observed for AEBt (44.7-54.2%; P<0.001), EFBt (49.3-58.2%; P<0.001) or indomethacin (64.6%, P<0.001, 10mg/kg). The growth of kidney cells (HEK) was inhibited by AEBt (IC(50) 182.6 µg/ml), EFBt (IC(50) 78.1 µg/ml) and AFBt (IC(50) 86.2 µg/ml), with lower effects on HTC hepatic cell (IC(50) 308.8 µg/ml, 396.5 µg/ml and 167.9 µg/ml, respectively). As evaluated by MTT test, AFBt exhibited cytotoxicity for HEK cells (IC(50) 372.5 µg/ml), but none for HTC ones; by the way, AFBt stimulated spleen cells (EC(50) 2.2 µg/ml) while cyclosporine, a cytotoxic reference drug inhibited them with IC(50) of 0.42 µg/ml; the IC(50) for doxorubicin for HEK and HTC cells was 0.28 µg/ml and 14.4 µg/ml, respectively, at 96h. No mutagenic potential was observed. Mice treatment with AEBt or AFBt at 42 mg/kg for 15 days altered the kidney relative weight, but not at 4.2mg/kg. Baccharis trimera did not change liver, spleen or popliteal lymph node relative weight. DNA damage index of kidney cells was observed on mice treated with AEBt/AFBt, but not on animals treated with EFBt, while DNA lesions were detected on liver cells only after AFBt treatment. The general activities of hepatic GST and Pi GST were reduced by EFBt and AFBt treatment, respectively. CONCLUSIONS: Baccharis trimera did not show mutagenicity, inhibited the GST activity, a hepatic detoxification enzyme, and induced in vivo (genotoxicity) and in vitro toxicological effects to kidney cells.


Assuntos
Anti-Inflamatórios/toxicidade , Baccharis/química , Extratos Vegetais/toxicidade , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Ensaio Cometa , Glutationa Transferase/metabolismo , Humanos , Técnicas In Vitro , Masculino , Camundongos , Extratos Vegetais/farmacologia , Ratos , Células Tumorais Cultivadas , Água
2.
Toxicol Lett ; 154(1-2): 69-80, 2004 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-15475180

RESUMO

This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.


Assuntos
Artrite Experimental/tratamento farmacológico , Baccharis/química , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Artrite Experimental/fisiopatologia , Aspartato Aminotransferases/sangue , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , DNA/biossíntese , DNA/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Extratos Vegetais/administração & dosagem
3.
J Pharm Pharmacol ; 56(1): 135-41, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14980011

RESUMO

We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branca, Leguminosae) seeds exhibit anti-arthritic activity. In the present work we show that the oleaginous extract obtained from P. pubescens seeds (OEP) exhibits acute or topic anti-edematogenic activity when tested in carrageenan-induced paw edema or in croton oil-induced ear edema assays, respectively. Four fractions were obtained from OEP by sequential liquid-liquid extraction. The anti-edematogenic properties were predominant in the hexanic fraction, which was further fractionated by HPLC, yielding three sub-fractions (PF1.1, PF1.2 and PF1.3). PF1.1 and PF1.3 showed potent acute and topic anti-edematogenic activity. The PF1.2 sub-fraction, although not active in the carrageenan assay, exhibited a potent anti-edematogenic activity in the croton oil-induced ear edema. This sub-fraction shows a maximum efficacy similar to indometacin in a lower dose. The PF1.1 sub-fraction presented a complex mixture containing furane diterpene derivatives of vouacapan. PF1.2 consists of a single substance, geranylgeraniol, as determined by GC/MS and NMR, while PF1.3 contains farnesol.


Assuntos
Edema/tratamento farmacológico , Fabaceae , Fitoterapia , Administração Tópica , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Injeções Intraperitoneais , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Sementes
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