title: Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of the cucurbitacins fraction from Wilbrandia ebracteata.
abstract: Wilbrandia ebracteata is a medicinal plant from South America used in folk medicine for the treatment of chronic rheumatic diseases. We have shown that the high performance liquid chromatography-characterized (HPLC) dichloromethane fraction isolated from Wilbrandia ebracteata (WEDC) inhibits the parameters observed in experimental models of inflammation in vivo and in vitro. In the present study, we extend our previous observations on the analgesic effects of WEDC by investigating its actions using the hot plate test and zymosan-induced writhing test in mice, as well as zymosan-induced arthritis in rats evaluating articular inflammatory pain, cell migration and determination of NO release into the joint exudate. The effect of WEDC on the activity of COX-1 and COX-2 in vitro and its ulcerogenic capacity in vivo were also investigated. The oral treatment of the animals with WEDC (1-10 mg/kg) produced a significant, dose-dependent reduction of articular incapacitation and abdominal contortions in the writhing test. The same effect was not observed in the hot plate and rota-rod tests. WEDC also reduced nitrite release into the zymosan-inflamed joints. In the evaluation of COX activity, we observed that WEDC was able to selectively inhibit COX-2 but not COX-1 activity in COS-7 cells. Moreover, WEDC treatment did not show gastrointestinal toxicity. Our data confirm the anti-nociceptive activities of the WEDC and indicate that this effect could be associated with inhibition of cyclooxygenase-2 (COX-2) and nitric oxide release. The effects could be attributed to cucurbitacins since several of these were isolated from the WEDC.
authors.affiliation: Pharmacy Course, Natural Products Research Group--GRUPNAT, University of South of Santa Catarina, Tubarão, Santa Catarina, Brazil. rrpeters@unisul.br
authors.forename: Rodrigo Rebelo
authors.initials: RR
authors.lastname: Peters
authors.forename: Patricia
authors.initials: P
authors.lastname: Baier Krepsky
authors.forename: Jarbas  Mota
authors.initials: J
authors.lastname: Siqueira-Junior
authors.forename: José Carlos
authors.initials: JC
authors.lastname: da Silva Rocha
authors.forename: Mirna
authors.initials: M
authors.lastname: Marques Bezerra
authors.forename: Ronaldo
authors.initials: R
authors.lastname: de Albuquerque Ribeiro
authors.forename: Artur José
authors.initials: AJ
authors.lastname: de Brum-Fernandes
authors.forename: Mareni
authors.initials: M
authors.lastname: Rocha Farias
authors.forename: Francisco Airton
authors.initials: FA
authors.lastname: Castro da Rocha
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ribeiro-do-Valle
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D019556:COS Cells / Q000187:drug effects / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects; D002522:Chlorocebus aethiops; D019662:Cucurbitaceae; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb; D006358:Hot Temperature; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010936:Plant Extracts; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases