Modulation of inflammatory responses by diterpene acids from Helianthus annuus L.
Fractionation of a petroleum ether extract of Helianthus annuus L. led to the isolation of three diterpene acids: grandiflorolic, kaurenoic and trachylobanoic acids. These compounds were studied for potential anti-inflammatory activity on the generation of inflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. At non-toxic concentrations, these compounds reduced, in a concentration-dependent manner nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) production, as well as expression of inducible nitric oxide synthase (NOS-2) and cyclooxygenase-2 (COX-2). All diterpenoids displayed significant in vivo anti-inflammatory activity and suppressed the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mouse ear edema. In addition, inhibition of myeloperoxidase (MPO) activity, an index of cellular infiltration, was observed. In summary, our results suggest that the inhibition of the expression of NOS-2, COX-2 and the release of inflammatory cytokines, is responsible for the anti-inflammatory effects of the diterpenoids isolated from H. annuus L. which likely contributes to the pharmacological action of sunflower.
Díaz-Viciedo
Rodrigo
R
Departamento de Farmacología Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Hortelano
Sonsoles
S
Girón
Natalia
N
Massó
Jose M
JM
Rodriguez
Benjamín
B
Villar
Angel
A
de Las Heras
Beatriz
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004224:Diterpenes / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D006368:Helianthus / Q000378:metabolism*; D007155:Immunologic Factors / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004224:Diterpenes; D007155:Immunologic Factors