title: From popular use to pharmacological validation: a study of the anti-inflammatory, anti-nociceptive and healing effects of Chenopodium ambrosioides extract.
abstract: ETHNO-PHARMACOLOGICAL RELEVANCE: Chenopodium ambrosioides (Amarantaceae) is an annual or perennial plant popularly known as 'erva de Santa Maria', 'mastruço' and 'erva-do-formigueiro'. This herb is used in folk medicine in the form of teas, poultices and infusions for inflammatory problems, contusions and lung infections, and as an anthelmintic and anti-fungal.
  
  
  OBJECTIVE
  The aim of the present study was to further the understanding of the anti-nociceptive, anti-inflammatory and wound healing effects of ethanol extract (EE) obtained from the leaves and stems of Chenopodium ambrosioides in animal models of acute pain, inflammation and wound healing, thus supporting its medicinal use for the treatment of pain and inflammatory conditions
  
  
  METHODS
  The anti-nociceptive activity of EE (150-500 mg/kg) was evaluated using the nociception induced by formalin (2.5%), prostaglandin-E(2) (PGE2; 3 nmol/paw), capsaicin (CAP, 1.6 μg/paw) and bradykinin (BK, 10 nmol/paw). The anti-inflammatory activity of EE (150-500 mg/kg) was evaluated in carrageenan- (Cg, 300 μg/paw), PGE(2)- (3 nmol/paw), substance P- (SP, 20 nmol/paw) and BK- (3 nmol/paw) induced paw oedema. The topical anti-inflammatory activity of EE (1%, 3% and 5%) was evaluated in arachidonic acid- (AA, 2mg/ear), oil croton- (1 μg/ear) and CAP- (250 μg/ear) induced ear oedema. The effect of this extract in the inhibition of the influx of neutrophil, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitric oxide (NO) and TNF-á levels was also determined using the mouse of pleurisy induced by Cg. The excision wound model in rats was used to evaluate the wound healing efficacy of EE (1%, 3% and 5%). To exclude the possible non-specific muscle relaxant or sedative effects of EE, mice motor performance was also evaluated with the rota-rod test.
  
  
  RESULTS
  EE (5% per ear) was effective in reducing ear oedema induced by croton oil by 78.09%, CAP by 70.85% and AA by 77.02%. EE (500 mg/kg; p.o.) also significantly inhibited paw oedema induced by Cg by 40%, PGE(2) by 51%, SP by 56% and BK by 57%. EE (500 mg/kg; p.o.) inhibited the cell influx of leucocytes by 78% and neutrophils by 53%, MPO activity by 62.22% and ADA activity by 23.07%, as well as NO by 77.77% and TNF-á levels by 50% in the fluid leakage due to the carrageenan-induced pleurisy. EE also inhibited the formalin-induced nociceptive in both phases of pain (neurogenic and inflammatory) at a dose of 500 mg/kg, resulting in inhibitions of 77.39% and 95.60%, respectively. EE (500 mg/kg; p.o.) was also effective in inhibiting the nociception induced by PGE(2) (68%), CAP (53%) and BK (32%). Topical application of EE (5%) on excision wounds caused a significant reduction in wound area when compared with the untreated controls. Finally, treatment with EE (150-500 mg/kg) did not show any significant alterations in motor performance or body temperature compared with the control group.
  
  
  CONCLUSIONS
  The results, including the inhibition of mediators (BK, NO, SP, PGE(2) and TNF-á) and enzyme (MPO and ADA) activity, validate the use of the plant under study for therapeutic treatment of anti-inflammatory, painful and wound healing processes.
authors.affiliation: Programa de Mestrado em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Liliane
authors.initials: L
authors.lastname: TrivellatoGrassi
authors.forename: Angela
authors.initials: A
authors.lastname: Malheiros
authors.forename: Christiane
authors.initials: C
authors.lastname: Meyre-Silva
authors.forename: Ziliani da Silva
authors.initials: Zda S
authors.lastname: Buss
authors.forename: Eduardo Dalmarco
authors.initials: ED
authors.lastname: Monguilhott
authors.forename: Tânia S
authors.initials: TS
authors.lastname: Fröde
authors.forename: Kathryn Ana Bortolini Simão
authors.initials: KA
authors.lastname: da Silva
authors.forename: Márcia Maria
authors.initials: MM
authors.lastname: de Souza
mesh_terms: D000700:Analgesics / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis* / Q000494:pharmacology / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D027464:Chenopodium ambrosioides / Q000737:chemistry*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D000431:Ethanol / Q000737:chemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000032:analysis / Q000302:isolation & purification; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D045442:Rotarod Performance Test / Q000379:methods; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D039821:Monoterpenes; D010936:Plant Extracts; D000431:Ethanol