ABSTRACT
Five phenylpropanoid glycosides isolated from Scrophularia scorodonia L. (Scrophulariaceae), namely angoroside A (1), angoroside C (2), angoroside D (3), acteoside (4) and isoacteoside (5), had been evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These compounds have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages and human platelets serve as source of COX-1 and 5-LOX, and mouse peritoneal macrophages stimulated with E. coli LPS are the means of testing for COX-2, NO and TNF-alpha activity. None of compounds assayed had a significant effect on LTC(4)-release from calcium ionophore-stimulated mouse peritoneal macrophages. However, the release of PGE(2) by mouse peritoneal macrophages stimulated with calcium ionophore was inhibited by most of these compounds. In the TXB(2)-release assay, acteoside (4), angoroside A (1) and angoroside C (2) showed a significant effect. These five compounds, except angoroside C (2) significantly inhibited LPS-induced PGE(2), NO and TNF-alpha in a concentration-dependent manner. In LPS-stimulated macrophages, the phenylpropanoid glycoside angoroside C (2) only had activity on NO. These results indicate that the pharmacology of these compounds may participate in the anti-inflammatory effect of Scrophularia scorodonia.
Subject(s)
Anti-Inflammatory Agents/immunology , Coumaric Acids/immunology , Plant Extracts/chemistry , Scrophularia/chemistry , Trisaccharides/immunology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Blood Platelets/drug effects , Blood Platelets/immunology , Calcimycin/pharmacology , Coumaric Acids/chemistry , Coumaric Acids/pharmacology , Cyclooxygenase 1 , Cyclooxygenase 2 , Humans , Ionophores/pharmacology , Isoenzymes/metabolism , Leukotriene C4/metabolism , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Membrane Proteins , Mice , Molecular Structure , Nitric Oxide/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Thromboxane B2/metabolism , Trisaccharides/chemistry , Trisaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In our ongoing research into anti-inflammatory compounds from Tanacetum microphyllum, four naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) and one sesquiterpene lactone (hydroxyachillin) isolated from this plant, were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These five compounds significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) in a concentration-dependent manner. In the tumour necrosis factor-alpha (TNF-alpha) assay, only centaureidin and hydroxyachillin significantly inhibited the accumulation of TNF-alpha. These results indicate that these compounds may contribute to the anti-inflammatory properties of T. microphyllum.
Subject(s)
Flavonoids/pharmacology , Lactones/pharmacology , Macrophages, Peritoneal/drug effects , Phytotherapy , Sesquiterpenes/pharmacology , Tanacetum , Animals , Dinoprostone/metabolism , Dose-Response Relationship, Drug , Flavonoids/administration & dosage , Flavonoids/therapeutic use , Lactones/administration & dosage , Lactones/therapeutic use , Lipopolysaccharides , Male , Mice , Nitric Oxide/metabolism , Plant Components, Aerial , Sesquiterpenes/administration & dosage , Sesquiterpenes/therapeutic use , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Four sesquiterpenes isolated from Jasonia glutinosa D.C. (Asteraceae), namely lucinone, glutinone, 5-epi-kutdtriol and kutdtriol, have been evaluated for their in vitro anti-inflammatory activity in cellular systems generating cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) metabolites. None of the compounds assayed had a significant effect on leukotriene C4 (LTC4)-release from calcium ionophore-stimulated mouse peritoneal cells. However, the release of prostaglandin E2 (PGE2) by mouse peritoneal cells stimulated with calcium ionophore was inhibited by these compounds, although with less potency than the reference drug indomethacin (IC50=0.24 microM). The IC50 values of the active compounds were: lucinone 42.69 microM, glutinone 3.61 microM, 5-epi-kutdtriol 1.28 microM and kutdtriol 39 microM. Of the tested compounds, only glutinone (IC50=24 microM) showed a significant effect on thromboxane B2 (TXB2)-release induced by calcium ionophore in human platelets, although with less potency than the reference drug ibuprofen (IC50=1.27 microM).
