title: Immunomodulatory effects of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone from Petasites hybridus and its synthesized benzoxazepine derivatives.
abstract: 1-(6-Hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone (1), isolated from the roots of Petasites hybridus L., and a series of synthetic benzoxazepine derivatives of compound 1 (2-6) were evaluated for their immunomodulatory effects. The compounds were evaluated for their effects on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using luminol- and lucigenin-based chemiluminescence (CL) assays, and their effect on chemotactic migration of PMNs was assessed using the Boyden chamber technique. Compound 1 exhibited stronger inhibition than acetylsalicylic acid (ASA) on luminol-enhanced CL of PMNs. It also inhibited PMN chemotaxis with an IC50 value comparable to that of ibuprofen. Of the compounds tested, 5 was the most effective in inhibiting luminol-enhanced CL and also strongly inhibited lucigenin-enhanced CL with IC50 values lower than that of ASA. Compound 2 was the most active in inhibiting migration of PMNs and was five times stronger than ibuprofen. The results suggest that compound 1 and its synthesized benzoxazepine derivatives, especially compounds 2 and 5, were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as leads for the development of new immunomodulatory agents.
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Khaleghi
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jantan
authors.forename: Laily Bin
authors.initials: LB
authors.lastname: Din
authors.forename: Wan A
authors.initials: WA
authors.lastname: Yaacob
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khalilzadeh
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
mesh_terms: D000328:Adult; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D036901:Petasites / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: C000590634:1-(6-hydroxy-2-isopropenyl-1-benzofuran-5-yl)-1-ethanone; D001572:Benzofurans; D007155:Immunologic Factors; D017382:Reactive Oxygen Species