title: Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models.
abstract: BACKGROUND
  Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed.
  
  
  METHODS
  The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA+and vacA+strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL-1β, TNF-a, IL -17, RANTES, IFN-γ and MIP-2) and anti-inflammatory (IL-10) cytokines.
  
  
  RESULTS
  HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity.
  
  
  CONCLUSIONS
  The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is independent of anti-H. pylori activity, with substances probably responsible for the pharmacological activity being flavonoids, quercetin and rutin. These results support the popular use of P. umbellatum leaves in the treatment of peptic ulcers.
authors.affiliation: Postgraduate Studies in Health Sciences, Faculty of Medicine, Universidade Federal de Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil.
authors.forename: Iberê Ferreira
authors.initials: IF
authors.lastname: da Silva Junior
authors.affiliation: Postgraduate Studies in Health Sciences, Faculty of Medicine, Universidade Federal de Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil.
authors.forename: Sikiru Olaitan
authors.initials: SO
authors.lastname: Balogun
authors.affiliation: Postgraduate Studies in Health Sciences, Faculty of Medicine, Universidade Federal de Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil.
authors.forename: Ruberlei Godinho
authors.initials: RG
authors.lastname: de Oliveira
authors.affiliation: Department of Basic Health Sciences, Faculty of Medicine, Universidade Federal de Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil.
authors.forename: Amílcar Sabino
authors.initials: AS
authors.lastname: Damazo
authors.affiliation: Department of Basic Health Sciences, Faculty of Medicine, Universidade Federal de Mato Grosso (UFMT), 78060-900 Cuiabá, MT, Brazil. Electronic address: taba@terra.com.br.
authors.forename: Domingos Tabajara de Oliveira
authors.initials: DTO
authors.lastname: Martins
mesh_terms: D019342:Acetic Acid; D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D012997:Solvents / Q000737:chemistry; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; D012997:Solvents; D000431:Ethanol; D008315:Malondialdehyde; D002374:Catalase; D005978:Glutathione; D019342:Acetic Acid
keywords: Anti-ulcer; Cytokines; Flavonoids; Mechanism of action; Piper umbellatum