| Description: |
Orsellinic acid is a novel benzoquinone ring precursor for antroquinonol and 4-acetylantroquinonol B, it formed from acetyl-coenzyme Q (CoQ) and malonyl-CoA via polyketide pathway.
Orsellinic acid can block platelet activating factor (PAF)-mediated neuronal apoptosis without affecting G-protein coupled receptor (PAFR)-mediated neuroprotection, it can effectively attenuate PAFR-independent neuronal apoptosis.
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| Targets: |
Caspase | PAFR |
| In vitro: |
| J Nat Prod. 2005 May;68(5):724-8 | | Globosumones A-C, cytotoxic orsellinic acid esters from the Sonoran desert endophytic fungus Chaetomium globosum.[Pubmed: 15921417] | Three new esters of Orsellinic acid, globosumones A-C (1-3), and three known compounds, Orsellinic acid (4), orcinol, and trichodion (5), were isolated from Chaetomium globosum endophytic on Ephedrafasciculata (Mormon tea).
METHODS AND RESULTS:
The structures of the new compounds 1-3 were established spectroscopically, which included 2D NMR experiments and 1H NMR studies on Mosher's ester derivatives. All compounds were evaluated for inhibition of cell proliferation in a panel of four cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), SF-268 (CNS glioma), and MIA Pa Ca-2 (pancreatic carcinoma), and normal human fibroblast cells (WI-38). Only globosumones A (1) and B (2) were found to be moderately active. |
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| In vivo: |
| J Neurochem. 2007 Oct;103(1):88-97. | | Platelet activating factor-induced neuronal apoptosis is initiated independently of its G-protein coupled PAF receptor and is inhibited by the benzoate orsellinic acid.[Pubmed: 17877634] | The bioactive lipid mediator platelet activating factor (PAF) is recognized as a key effecter of neuronal apoptosis, yet it is not clear whether its G-protein coupled receptor (PAFR) initiates or prevents PAF neurotoxicity.
METHODS AND RESULTS:
Using PAFR-/- and congenic wild-type mice, we show that PAF triggers caspase-3/7 activity and neuronal death in PAFR-/- but not PAFR+/+ cerebellar granule neurons. Restoring receptor expression by recombinant adenoviral infection protected cells from PAF challenge. Neuronal death was not mediated by nitric oxide or N-methyl-d-aspartate receptor signaling given that N-nitro-l-arginine methyl ester and MK-801 did not inhibit PAF-induced neuronal loss in PAFR-/- neurons. To intervene in PAFR-independent neurotoxicity, the anti-apoptotic actions of three structurally distinct PAF antagonists were compared to a panel of plant and fungal benzoic acid derivatives. We found that the PAF antagonist BN 52021 but not FR 49175 or CV 3988 inhibited PAFR-independent neurotoxicity. Orsellinic acid, a fungal-derived benzoic acid, blocked PAF-mediated neuronal apoptosis without affecting PAFR-mediated neuroprotection.
METHODS AND RESULTS:
These findings demonstrate that PAF can transduce apoptotic death in primary neurons independently of its G-protein coupled receptor, that PAFR activation is neuroprotective, and that orsellinic acid effectively attenuates PAFR-independent neuronal apoptosis. |
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