title: Biruloquinone, an acetylcholinesterase inhibitor produced by lichen-forming fungus Cladonia macilenta.
abstract: At present, acetylcholinesterase (AChE) inhibitors are the first group of drugs to treat mild to moderate Alzheimer's disease (AD). Although beneficial in improving cognitive and behavioral symptoms, the effectiveness of AChE inhibitors has been questioned since they do not delay or prevent neurodegeneration in AD patients. Therefore, in the present study, in order to develop new and effective anti-AD agents from lichen products, both the AChE inhibitory and the neuroprotective effects were evaluated. The AChE inhibitory assay was performed based on Ellman's reaction, and the neuroprotective effect was evaluated by using the MTT method on injured PC12 cells. One AChE inhibitor (IC50 = 27.1 microg/ml) was isolated by means of bioactivity-guided isolation from the extract of lichen-forming fungus Cladonia macilenta, which showed the most potent AChE inhibitory activity in previous screening experiment. It was then identified as biruloquinone by MS, and 1H- and 13C-NMR analyses. The inhibitory kinetic assay suggested that biruloquinone is a mixed-II inhibitor on AChE. Meanwhile, biruloquinone improved the viability of the H2O2- and beta-amyloid-injured PC12 cells at 1 to 25 microg/ml. The protective effects are proposed to be related to the potent antioxidant activities of biruloquinone. These results imply that biruloquinone has the potential to be developed as a multifunctional anti- AD agent.
authors: Department of Biology and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, China.
authors: Heng
authors: H
authors: Luo
authors: Changtian
authors: C
authors: Li
authors: Jin Cheol
authors: JC
authors: Kim
authors: Yanpeng
authors: Y
authors: Liu
authors: Jae Sung
authors: JS
authors: Jung
authors: Young Jin
authors: YJ
authors: Koh
authors: Jae-Seoun
authors: JS
authors: Hur
mesh_terms: D000110:Acetylcholinesterase; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001203:Ascomycota / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D018696:Neuroprotective Agents / Q000302:isolation & purification* / Q000378:metabolism*; D011809:Quinones / Q000302:isolation & purification* / Q000378:metabolism*; D051381:Rats; D013194:Staining and Labeling / Q000379:methods; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D011809:Quinones; D013778:Tetrazolium Salts; D013844:Thiazoles; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; C022616:thiazolyl blue