Multi-functional activities of citrus flavonoid narirutin in Alzheimer's disease therapeutics: An integrated screening approach and in vitro validation

International Journal of Biological Macromolecules
Sandipan Chakraborty, Soumalee Basu

Abstract

Alzheimer's disease (AD) is a complex disorder and the disease mechanism is yet to be properly characterized. Over the years, "amyloid cascade" emerges as principal pathogenic event in AD. β-Secretase 1 (BACE1) controls the rate-limiting step in amyloid beta (Aβ) generation and Aβ rapidly aggregates to form neurotoxic amyloid fibrils. Oxidative stress is one of the principal mediators of the observed neurotoxicity of amyloid fibril. The disease pathogenesis involves induction of multiple signaling cascades and the cross-talk therein. Thus inhibiting multiple targets could be an attractive therapeutic strategy. Here, a multi-target virtual screening protocol has been devised and used to screen an in house developed phytochemical library. Narirutin comes out as a multi-potent phytochemical. Steady-state and time-resolved fluorescence along with molecular modelling studies demonstrate its binding to the BACE1 active site that induces a conformational transition of the protein from open to closed form which precludes substrate recognition. Narirutin possesses strong Aβ aggregation inhibitory potential, evident from ANS and Thioflavin-T binding assay and confirmed by AFM study. ABTS(·+) scavenging assay shows moderate antioxidant ac...Continue Reading

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Nov 23, 2016·International Journal of Biological Macromolecules·Sandipan Chakraborty, Soumalee Basu

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Citations

Aug 3, 2018·Natural Products and Bioprospecting·Marines Marli Gniech Karasawa, Chakravarthi Mohan
Apr 12, 2020·Journal of Clinical Medicine·Mehdi Sharifi-RadJavad Sharifi-Rad
Aug 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Thai-Son TranKhac-Minh Thai
Sep 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jesús Alfredo Araujo-LeónZulema Cantillo-Ciau
Feb 14, 2021·International Journal of Biological Macromolecules·Sandipan ChakrabortySoumalee Basu
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Oluwafemi Adeleke OjoGaber El-Saber Batiha

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