An extract of Apium graveolens var. dulce leaves: structure of the major constituent, apiin, and its anti-inflammatory properties.
Flavonoids, natural compounds widely distributed in the plant kingdom, are reported to affect the inflammatory process and to possess anti-inflammatory as well as immunomodulatory activity in-vitro and in-vivo. Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is one of the inflammatory mediators, the effects of the ethanol/water (1:1) extract of the leaves of Apium graveolens var. dulce (celery) on iNOS expression and NO production in the J774.A1 macrophage cell line stimulated for 24 h with Escherichia coli lipopolysaccharide (LPS) were evaluated. The extract of A. graveolens var. dulce contained apiin as the major constituent (1.12%, w/w, of the extract). The extract and apiin showed significant inhibitory activity on nitrite (NO) production in-vitro (IC50 0.073 and 0.08 mg mL(-1) for the extract and apiin, respectively) and iNOS expression (IC50 0.095 and 0.049 mg mL(-1) for the extract and apiin, respectively) in LPS-activated J774.A1 cells. The croton-oil ear test on mice showed that the extract exerted anti-inflammatory activity in-vivo (ID50 730 microg cm(-2)), with a potency seven-times lower than that of indometacin (ID50 93 microg cm(-2)), the non-steroidal anti-inflammatory drug used as reference. Our results clearly indicated the inhibitory activity of the extract and apiin in-vitro on iNOS expression and nitrite production when added before LPS stimulation in the medium of J774.A1 cells. The anti-inflammatory properties of the extract demonstrated in-vivo might have been due to reduction of iNOS enzyme expression.
Mencherini
T
T
Dipartimento di Scienze Farmaceutiche, University of Salerno, Italy.
Cau
A
A
Bianco
G
G
Della Loggia
R
R
Aquino
R P
RP
Autore
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D000077102:Apium / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves; D010945:Plants, Edible
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D009569:Nitric Oxide; C012186:apiin; D052247:Nitric Oxide Synthase Type II