Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.
One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by oleanonic acid with an IC50 of 17 microM. Negligible differences were observed in the response of both triterpenes to DPP, bradykinin, and phospholipase A2, while oleanonic acid was more active on the dermatitis by TPA and on the in vitro leukotriene formation. In conclusion, the presence of a ketone at C-3 implies an increase in the inhibitory effects on models related to 5-lipoxygenase activity and on associated in vivo inflammatory processes.
Giner-Larza
E M
EM
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Máñez
S
S
Recio
M C
MC
Giner
R M
RM
Prieto
J M
JM
Cerdá-Nicolás
M
M
Ríos
J L
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004431:Ear, External / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005528:Foot / Q000473:pathology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007975:Leukotriene B4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D027927:Pistacia / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes; C450739:oleanonic acid; D007975:Leukotriene B4; D009828:Oleanolic Acid; D009195:Peroxidase; C022616:thiazolyl blue