title: Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.
abstract: BACKGROUND
  Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata.
  
  
  METHODS
  The inner stem bark extract of Cedrela odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500 mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500 mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma.
  
  
  RESULTS
  The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose of the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but reduced the triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity.
  
  
  CONCLUSIONS
  Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases and glucose transporter inhibitors and antioxidant property.
authors.affiliation: Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Morenna Alana
authors.initials: MA
authors.lastname: Giordani
authors.affiliation: Natural Products Research Laboratory, Faculty of Medicine, Federal University of Tocantins (UFT), Av. NS15, Palmas, CEP: 77020-210, Palmas, Tocantins, Brazil.
authors.forename: Thiago Carvalho Mamede
authors.initials: TC
authors.lastname: Collicchio
authors.affiliation: Natural Products Research Laboratory, Faculty of Medicine, Federal University of Tocantins (UFT), Av. NS15, Palmas, CEP: 77020-210, Palmas, Tocantins, Brazil.
authors.forename: Sergio Donizeti
authors.initials: SD
authors.lastname: Ascêncio
authors.affiliation: Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Domingos Tabajara de Oliveira
authors.initials: DT
authors.lastname: Martins
authors.affiliation: Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Sikiru Olaitan
authors.initials: SO
authors.lastname: Balogun
authors.affiliation: Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Isanete Geraldini Costa
authors.initials: IG
authors.lastname: Bieski
authors.affiliation: Department of Clinical Veterinary Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Leilane Aparecida
authors.initials: LA
authors.lastname: da Silva
authors.affiliation: Department of Clinical Veterinary Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Edson Moleta
authors.initials: EM
authors.lastname: Colodel
authors.affiliation: Department of Clinical Veterinary Medicine, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Roberto Lopes
authors.initials: RL
authors.lastname: de Souza
authors.affiliation: Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Damiana Luiza Pereira
authors.initials: DL
authors.lastname: de Souza
authors.affiliation: Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Suélem Aparecida
authors.initials: SA
authors.lastname: de França
authors.affiliation: Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil.
authors.forename: Claudia Marlise Balbinotti
authors.initials: CM
authors.lastname: Andrade
authors.affiliation: Department of Chemistry, Biochemistry Laboratory, Federal University of Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367, Boa Esperança, CEP: 78060-900, Cuiabá, Mato Grosso, Brazil. Electronic address: nairhonda@terra.com.br.
authors.forename: Nair Honda
authors.initials: NH
authors.lastname: Kawashita
mesh_terms: D000818:Animals; D031587:Cedrela / Q000737:chemistry*; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage*
chemical_list: D010936:Plant Extracts; D013395:Sucrose; D005947:Glucose
keywords: Anti-hyperglycemic; Antidiabetic; Hypolipidemic; In vivo antioxidant; Polyphenols