Oleic Acid and Linoleic Acid from Tenebrio molitor Larvae Inhibit BACE1 Activity in vitro: Molecular Docking Studies

• Published in: Journal of medicinal food Vol. 17; no. 2; pp. 284 - 289
• Main Authors: Youn, Kumju, Yun, Eun-Young, Lee, Jinhyuk, Kim, Ji-Young, Hwang, Jae-Sam, Jeong, Woo-Sik, Jun, Mira
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.02.2014
• Subjects: Alzheimer disease; Alzheimer Disease - enzymology; ammonia; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - chemistry; Amyloid Precursor Protein Secretases - metabolism; Animals; Aspartic Acid Endopeptidases - antagonists & inhibitors; Aspartic Acid Endopeptidases - chemistry; Aspartic Acid Endopeptidases - metabolism; Enzyme Inhibitors - chemistry; gas chromatography; guidelines; hexane; Humans; inhibitory concentration 50; Kinetics; Larva - chemistry; Larva - growth & development; larvae; linoleic acid; Linoleic Acid - chemistry; long chain unsaturated fatty acids; Molecular Docking Simulation; molecular models; natural resources; nuclear magnetic resonance spectroscopy; oleic acid; Oleic Acid - chemistry; pharmacology; Tenebrio - chemistry; Tenebrio - growth & development; Tenebrio molitor; thin layer chromatography
• ISSN: 1557-7600; 1557-7600
• DOI: 10.1089/jmf.2013.2968

In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.