Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
Hyun Ah JungJae Sue Choi

Abstract

Since the action of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD), the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. In our ongoing research aimed at identifying anti-AD remedies derived from maritime plants, we evaluated the BACE1 inhibitory activities of fucosterol and fucoxanthin from Ecklonia stolonifera and Undaria pinnatifida. In vitro anti-AD activities were performed via BACE1 inhibition assays, as well as enzyme kinetic and molecular docking predictions. Based on enzyme-based assays, fucosterol and fucoxanthin showed noncompetitive and mixed-type inhibition, respectively, against BACE1. In addition, docking simulation results demonstrated that the Lys224 residue of BACE1 interacted with one hydroxyl group of fucosterol, while two additional BACE1 residues (Gly11 and Ala127) interacted with two hydroxyl groups of fucoxanthin. Moreover, the binding energy of fucosterol and fucoxanthin was negative (-10.1 and -7.0 kcal/mol), indicating that hydrogen bonding may stabilize the open form of the enzyme and potentiate tight binding of the active site of BACE1, resulting in more effective BACE1 inhibition. The res...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
May 1, 1997·Journal of Natural Products· Atta-ur-RahmanM I Choudhary
Aug 1, 2006·Lancet·Kaj BlennowHenrik Zetterberg
Feb 20, 2007·Mini Reviews in Medicinal Chemistry·Quan LiuGeorge Perry
Sep 27, 2007·Journal of Agricultural and Food Chemistry·Nakkarike M SachindraKazuo Miyashita
May 21, 2008·Cell Stress & Chaperones·Sun Don Kim, Jinoh Kim
Jun 20, 2008·Journal of Neuroinflammation·Magdalena SastreSteve M Gentleman
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Arun K GhoshJordan Tang
Apr 30, 2011·Molecular Neurodegeneration·Hui Zheng, Edward H Koo
Nov 19, 2011·Nature Reviews. Drug Discovery·Katrin Legg
May 23, 2012·Marine Drugs·Nicolantonio D'OrazioGraziano Riccioni
Jun 28, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Soo-Jin HeoWon-Kyo Jung

❮ Previous
Next ❯

Citations

Dec 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ting GuNian-Guang Li
Jan 17, 2019·Journal of Cellular and Molecular Medicine·Jia WangXiangyang Zou
Feb 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aditi WagleJae Sue Choi
Oct 28, 2019·Current Alzheimer Research·Anuruddhika Udayangani RathnayakeHee-Guk Byun
Aug 26, 2017·Archives of Pharmacal Research·Prashamsa KoiralaJae Sue Choi
Nov 14, 2019·Neural Regeneration Research·Melissa SchepersTim Vanmierlo
Nov 11, 2019·International Journal of Molecular Sciences·Johant Lakey-BeitiaK S Rao
Jun 24, 2017·Frontiers in Aging Neuroscience·Emiliano Peña-AltamiraBarbara Monti
Jan 18, 2018·Natural Product Reports·John W BluntMichèle R Prinsep
Jul 28, 2019·Antioxidants·Tomasz M Karpiński, Artur Adamczak
Oct 23, 2020·The Journal of International Medical Research·Guoliu YeCaizhi Wang
Oct 31, 2020·Critical Reviews in Food Science and Nutrition·Seyed Fakhreddin HosseiniDavid Julian McClements
Nov 18, 2020·Pest Management Science·Rafael de Almeida BarrosMaria G de Almeida Oliveira
Apr 11, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Md Abdul HannanIl Soo Moon
Aug 3, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Janani ManochkumarSiva Ramamoorthy
Aug 27, 2021·Marine Drugs·Salar Hafez Ghoran, Anake Kijjoa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.