title: Immunomodulatory and anti-inflammatory activity of selected osthole derivatives.
abstract: From osthole [7-methoxy-8-(3-methyl-but-2-enyl)-chromen-2-one] (I), obtained by selective extraction of Peucedanum ostruthium (L.) W. Koch roots, ostholic acid (II) was synthetized as a result of its oxidation with chromium trioxide. From ostholic acid, through its chloride, four amides were obtained: the morpholide 1, the p-chloro-benzylamide 2, the piperidine 3 and the N-methyl-piperazide 4. Except for 1, other compounds have not been described before. The amides 1-4 and their precursor osthole (I) were tested for their potential activities in selected immunological assays. The compounds showed moderate inhibitory activity in the humoral immune response to sheep erythrocytes in mice in vitro, and 4 was the most suppressive. The effects of 1 and 3 on concanavalin A- and pokeweed mitogen-induced mouse splenocyte proliferation were inhibitory and those of 4 stimulatory. The compounds were also tested for their activity on tumour necrosis factor a and interleukin 6 production, induced by lipopolysaccharide, in cultures of rat peritoneal cells and human peripheral blood mononuclear cells. Compounds 1, 3 and 4 inhibited tumour necrosis factor a (rat cells), whereas compound 2 stimulated the production of both cytokines. Compounds 1, 2 and 3 were also strongly inhibitory on tumour necrosis factor a production in human blood cells (73, 78 and 80% inhibition at 10 microg/ml, respectively). On the other hand, 2 and 4 stimulated the interleukin 6 production (2- to 3-fold stimulation). In addition, 2 and 4 suppressed the carrageenan-induced inflammation in mice (56.5% and 68.3% inhibition, respectively). In summary, the compounds predominantly displayed suppressive and antiinflammatory activities in the investigated models.
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, R. Weigla str. 12, 53-114, Wroclaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
authors.forename: Jolanta
authors.initials: J
authors.lastname: Artym
authors.forename: Wojciech
authors.initials: W
authors.lastname: Cisowski
authors.forename: Irena
authors.initials: I
authors.lastname: Mazol
authors.forename: Maciej
authors.initials: M
authors.lastname: Włodarczyk
authors.forename: Michał
authors.initials: M
authors.lastname: Gleńsk
mesh_terms: D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000917:Antibody Formation; D019661:Apiaceae / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004121:Dimethyl Sulfoxide; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016207:Cytokines; D007155:Immunologic Factors; D010936:Plant Extracts; D003208:Concanavalin A; C046627:osthol; D004121:Dimethyl Sulfoxide