Anti-inflammatory activity of two cucurbitacins isolated from Cayaponia tayuya roots.
Fractionation of an anti-inflammatory extract from Cayaponia tayuya roots yielded two active compounds, identified as 23,24-dihydrocucurbitacin B (1) and cucurbitacin R (2). Both were evaluated for their anti-inflammatory activity on several experimental models of pain and inflammation. In addition, their cytotoxicity and effects on leukotriene B4 (LTB4) formation were evaluated in rat polymorphonuclear leukocytes. Both compounds showed activity in the following models: carrageenan-induced mouse paw oedema (1, 4 mg/kg p.o., 46% inhibition at 3 h), phospholipase A2-induced mouse paw oedema (2, 3 mg/kg i.p., 61% inhibition at 60 min), serotonin-induced mouse paw oedema (1 and 2, 0.5 mg/kg s.c., 73% and 79% inhibition, respectively), 12- O-tetradecanoylphorbol 13-acetate (TPA)-induced acute ear oedema (2, 36% inhibition at 4 mg/kg p.o., and 87% inhibition at 0.1 mg/ear topically). The compounds were also active against the inflammation induced by repeated application of TPA on mouse ears, affecting both the oedema itself (1 and 2 at 0.1 mg/ear, 44% and 56% inhibition, respectively) as well as cell infiltration (68% and 69%, respectively). The activity of both compounds against oedema induced by serotonin was not modified by the glucocorticoid receptor antagonist mifepristone; however, the protein synthesis inhibitor cycloheximide abolished the anti-inflammatory response in both cases. Neither compound modified the production of LTB4 in rat polymorphonuclear leukocytes, nor did they exhibit analgesic properties at the dose assayed.
Recio
M Carmen
MC
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Prieto
Maite
M
Bonucelli
Marina
M
Orsi
Cecilia
C
Máñez
Salvador
S
Giner
Rosa M
RM
Cerdá-Nicolás
M
M
Ríos
José-Luis
JL
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D019662:Cucurbitaceae; D054728:Cucurbitacins; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010741:Phospholipases A; D054467:Phospholipases A2; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010936:Plant Extracts; D014315:Triterpenes; D007975:Leukotriene B4; D054728:Cucurbitacins; D002351:Carrageenan; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; C478086:23,24-dihydrocucurbitacin B