Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of the cucurbitacins fraction from Wilbrandia ebracteata.
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.
Peters
Rodrigo Rebelo
RR
Pharmacy Course, Natural Products Research Group--GRUPNAT, University of South of Santa Catarina, Tubarão, Santa Catarina, Brazil. rrpeters@unisul.br
Baier Krepsky
Patricia
P
Siqueira-Junior
Jarbas  Mota
J
da Silva Rocha
José Carlos
JC
Marques Bezerra
Mirna
M
de Albuquerque Ribeiro
Ronaldo
R
de Brum-Fernandes
Artur José
AJ
Rocha Farias
Mareni
M
Castro da Rocha
Francisco Airton
FA
Ribeiro-do-Valle
Rosa Maria
RM
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
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010936:Plant Extracts; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases