title: Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation.
abstract: The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi-synthetic analogs (6 and 7) on thromboxane B(2) (TXB(2)) and superoxide anion (O(2)(-)) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB(2) (IC(50)=0.20-4.69μM) with low lactate dehydrogenase release and minimal mitochondrial dehydrogenase inhibition. While a lack of O(2)(-) inhibition would suggest that Hymeniacidon sp. metabolites and derivatives inhibit TXB(2) synthesis by a cyclooxygenase-dependent mechanism, their pharmacologic potency and limited in vitro cytotoxicity warrants further investigation to develop them as lead compounds to modulate enhanced TBX(2) release by activated microglia in neuroinflammatory disorders.
authors.affiliation: Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555, 31st Street, Downers Grove, IL 60515, USA.
authors.forename: Alejandro M S
authors.initials: AM
authors.lastname: Mayer
authors.forename: Edward
authors.initials: E
authors.lastname: Avilés
authors.forename: Abimael D
authors.initials: AD
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D008070:Lipopolysaccharides; D013481:Superoxides; D013929:Thromboxane B2; D010088:Oxidoreductases; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases