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Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B 2 generation
Author(s) -
Mayer Alejandro M,
Chaudhry Saba,
Hall Mary L,
Aviles Edward,
Rodriguez Abimael D
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.966.1
Subject(s) - sponge , chemistry , lactate dehydrogenase , superoxide dismutase , superoxide , cyclooxygenase , thromboxane , stereochemistry , biochemistry , pharmacology , biology , enzyme , immunology , platelet , botany
Neuroinflammation appears to involve release of thromboxane B 2 (TXB 2 ) and superoxide anion (O 2 − ) by brain microglia (BMG). The purpose of this investigation was to determine the effect of five Hymeniacidon sp. amphilectane metabolites (HsH2.6, HsH1.11, HsH2.13, HsH2.29_456, and HsH2.11.X7.3) and two semi‐synthetic analogs (HsH1.11x and HsH1.11X2) on TXB 2 and O 2 − generation from E. coli LPS‐activated rat BMG. Short and long term cell viability was assessed by lactate dehydrogenase (LDH) release (1.5 h) and mitochondrial dehydrogenase (MTH) activity (2.5–18 h), respectively. O 2 − levels were determined via superoxide dismutase‐inhibitable reduction of ferricytochrome C and TXB 2 by EIA. Results were the following (n=3–4): all Hymeniacidon sp. metabolites and analogs potently inhibited TXB 2 (IC 50 =0.20–5.69 μM) with low LDH release and minimal MTH inhibition. Comparison of IC 50 of closely related amphilectane diterpenes HsH2.13 (IC 50 ~0.20 μM) and HsH1.11 (IC 50 ~0.23 μM) supports the observation that bioactivity is associated with presence of two isonitrile groups. However, the amphilectane diterpenoid skeleton plays a significant role, as suggested by comparison between IC 50 of these two compounds and HsH1.11X2 (IC 50 ~3.14 μM), where original isonitriles have been replaced by formamide groups. Lack of O 2 − inhibition would appear to suggest that all Hymeniacidon sp. metabolites and derivatives inhibit TXB 2 synthesis by a cyclooxygenase‐dependent mechanism. Supported by Midwestern University and the RISE and SCORE Programs, University of Puerto Rico at the Río Piedras Campus.