title: Evaluation of the safety, gastroprotective activity and mechanism of action of standardised leaves infusion extract of Copaifera malmei Harms.
abstract: BACKGROUND
  Copaifera malmei Harms (Fabaceae) is a plant that occurs in the central region of Brazil, where the plant's leaves infusion is popularly used to treat gastric ulcer and inflammatory diseases. This study was aimed to investigate the gastroprotective activity and mode of action of the plants' leaves infusion in order to establish the scientific basis for such usage, and to assess its potential as a source of an anti-ulcer agent.
  
  
  METHODS
  Leaves infusion extract of the plant (SIECm) was prepared, freeze dried and lyophilised. Its qualitative and quantitative phytochemical constituents were investigated using TLC and HPLC techniques. The safety profile was evaluated on CHO-k1 epithelial cells viability using the Alamar blue assay, and by acute toxicity test in mice. The gastroprotection and anti-ulcer efficacy of the SIECm (25, 100 and 400mg/kg, p.o.) were tested using acute (acidified ethanol, piroxicam and water restrain stress), and chronic (acetic acid) experimental ulcer models. The plausible mode of action of the SIECm was assessed using gastric secretion, gastric barrier mucus, nitric oxide, and its antioxidant (myeloperoxidase and catalase) effects in mice and rats. The histopathological analyses of the ulcerated tissues as well as the extract's activity on Helicobacter pylori were also investigated.
  
  
  RESULTS
  Phytochemical tests indicated the presence of mainly phytosterols, phenolics and flavonoids. The SIECm exhibited no cytotoxic effects on the CHO-k1 cells, and no oral acute toxicity in mice. It prevented against the acute induced ulcerations by enhancing gastroprotection through gastric mucus production, NO modulation, antioxidant, reduced gastric secretion and enhanced chronic ulcers healing process, as shown by reduction/prevention of epithelial and vascular damage, in addition to reduction in leucocyte infiltration. The SIECm however did not exhibit activity against H. pylori.
  
  
  CONCLUSIONS
  The SIECm is safe, contain useful phytochemicals and exhibited significant gastroprotective/anti-ulcer effects. The results justify its folkloric usage, and provided scientific evidence of its potential as a source of new phytodrug to treat gastric ulcers.
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil; Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development (NIPRD), Abuja, Nigeria.
authors.forename: Bulus
authors.initials: B
authors.lastname: Adzu
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Sikiru Olaitan
authors.initials: SO
authors.lastname: Balogun
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Pavan
authors.affiliation: Laboratório de Pesquisa em Produtos Naturais, Curso de Medicina, Universidade Federal do Tocantins (UFT), Palmas, Brazil.
authors.forename: Sérgio Donizeti
authors.initials: SD
authors.lastname: Ascêncio
authors.affiliation: Laboratório de Pesquisa em Produtos Naturais, Curso de Medicina, Universidade Federal do Tocantins (UFT), Palmas, Brazil.
authors.forename: Ilsamar Mendes
authors.initials: IM
authors.lastname: Soares
authors.affiliation: Departamento da Biotecnologia, Universidade Federal do Tocantins (UFT), Gurupi, Brazil.
authors.forename: Raimundo Wagner Souza
authors.initials: RW
authors.lastname: Aguiar
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Reginaldo Vicente
authors.initials: RV
authors.lastname: Ribeiro
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Ângela Márcia Selhorst e Silva
authors.initials: ÂM
authors.lastname: Beserra
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Ruberlei Godinho
authors.initials: RG
authors.lastname: de Oliveira
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Larissa Irene
authors.initials: LI
authors.lastname: da Silva
authors.affiliation: Área de Histologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil.
authors.forename: Amílcar Sabino
authors.initials: AS
authors.lastname: Damazo
authors.affiliation: Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil. Electronic address: taba@terra.com.br.
authors.forename: Domingos Tabajara de Oliveira
authors.initials: DT
authors.lastname: Martins
mesh_terms: D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D000431:Ethanol; D007887:Fabaceae; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D009093:Mucus / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D010894:Piroxicam; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023382:Toxicity Tests, Acute
chemical_list: D000897:Anti-Ulcer Agents; D010936:Plant Extracts; D010894:Piroxicam; D009569:Nitric Oxide; D000431:Ethanol; D002374:Catalase; D009195:Peroxidase; D019342:Acetic Acid
keywords: Acute toxicity; Copaifera malmei; Gastroprotection; Leaves infusion; Phytochemicals