title: Antiophidic activity of the extract of the Amazon plant Humirianthera ampla and constituents.
abstract: BACKGROUND
  Although serotherapy against snakebite has been discovered more than one hundred years ago, antivenom is not available all over Brazil. The use of plants from folk medicine is common mainly in the Brazilian Amazon area. One of these plants is named Humirianthera ampla (HA).
  
  
  METHODS
  We have investigated HA extract and constituents' antiophidic activity in different experimental protocols against some Bothrops snake venoms (Bothrops jararacussu, Bothrops atrox and Bothrops jararaca). The protocols investigated include phospholipase, proteolytic, pro-coagulant, hemorrhagic, edematogenic and myotoxic activities induced by these venoms in Swiss mice.
  
  
  RESULTS
  All the venoms caused an increase in the rate of creatine kinase (CK) release from isolated muscles, indicating damage to the sarcolemma. The crude extract of HA decreased the myotoxic activity in a concentration-dependent fashion. The presence of HA 300 μg/mL decreased up to 96% of Bothrops jararacussu and 94% of Bothrops atrox myotoxicity after 90 min of exposure. In vivo myotoxicity of Bothrops atrox venom was decreased in 75% when the venom was preincubated with HA 500 mg/kg. Similar results were observed with lupeol against Bothrops jararacussu and Bothrops atrox venoms. The hemorrhagic activity was evaluated by intradermal injection of Bothrops atrox venom. Preincubation and oral pre- and posttreatment with HA decreased hemorrhage by 100%, 45% and 45%, respectively. Bothrops atrox venom also induced formation of edema, which was significantly inhibited by pre- and posttreatment with HA. All the venoms showed extensive pro-coagulating properties, and these activities were inhibited by up to 90% with HA, which presented concentration-dependent inhibition. Finally, proteolytic and phospholipase activities of the venoms were all inhibited by increasing concentrations of HA, lupeol and sitosterol. The inhibition of these activities might help explain the actions against in vivo myotoxicity and the in vivo effects observed, i.e., edema, myotoxicity, pro-coagulation and hemorrhage.
  
  
  CONCLUSIONS
  Altogether, our results give support for the popular use of HA extracts in cases of accidents with snakes, suggesting that it can be used as an adjunct in the management of venomous snakebites.
authors.affiliation: Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Avenida Brigadeiro Trompowski, Rio de Janeiro, RJ 21941-590, Brazil.
authors.forename: Marcelo Abrahão
authors.initials: MA
authors.lastname: Strauch
authors.forename: Marcelo Amorim
authors.initials: MA
authors.lastname: Tomaz
authors.forename: Marcos
authors.initials: M
authors.lastname: Monteiro-Machado
authors.forename: Hilmar Dias
authors.initials: HD
authors.lastname: Ricardo
authors.forename: Bruno Lemos
authors.initials: BL
authors.lastname: Cons
authors.forename: Fabrício F A
authors.initials: FF
authors.lastname: Fernandes
authors.forename: Camila Z
authors.initials: CZ
authors.lastname: El-Kik
authors.forename: Mariângela Soares
authors.initials: MS
authors.lastname: Azevedo
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology / Q000627:therapeutic use*; D017837:Bothrops; D001938:Brazil; D003435:Crotalid Venoms / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004487:Edema / Q000188:drug therapy; D000431:Ethanol / Q000737:chemistry; D006470:Hemorrhage / Q000188:drug therapy; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D051379:Mice; D009132:Muscles / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots / Q000737:chemistry; D012855:Sitosterols / Q000494:pharmacology / Q000627:therapeutic use*; D000094042:Lupanes
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; D000431:Ethanol; D053978:Pentacyclic Triterpenes; D010740:Phospholipases; D010936:Plant Extracts; D012855:Sitosterols; C025473:gamma-sitosterol; C010480:lupeol; D000094042:Lupanes