The ambrosanolide cumanin inhibits macrophage nitric oxide synthesis: some structural considerations.
Since its role in inflammatory diseases was recognized, nitric oxide (NO) has become an important mediator to evaluate anti-inflammatory agents. Sesquiterpene lactones, which occur in several medicinal plants, inhibit the NO production in macrophage-like cells. This action is probably due to a 1,4 addition reaction between its alpha,beta-unsaturated carbonyl group with sulfhydryl (SH)-containing compounds. For this reason it is believed that these compounds are cytotoxic, which restricts their therapeutic use. In this contribution, the ability of the ambrosanolide-type sesquiterpene lactone cumanin (from the Asteraceae Ambrosia psilostachya) to inhibit NO biosynthesis was evaluated in lipopolisaccharide-induced peritoneal murine macrophages and its cytotoxicity was assessed in the MTT assay. Cumanin showed a potent inhibitory effect in NO production (IC(50) = 9.38+/-0.38 microM) with low cytotoxicity. The 1,4-addition reaction of thiols was slow, which does not explain the inhibition of NO production but does explain the low cytotoxicity of cumanin with respect to other lactones.
Lastra
A L
AL
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Interior s/n CP 04510, México, D.F., Mexico.
Ramírez
T O
TO
Salazar
L
L
Martínez
M
M
Trujillo-Ferrara
J
J
D031164:Ambrosia; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D010936:Plant Extracts; D012717:Sesquiterpenes; D009569:Nitric Oxide