Dual modulators of aggregation and dissociation of amyloid beta and tau: In vitro, in vivo, and in silico studies of Uncaria rhynchophylla and its bioactive components

Kim, Sujin; Nam, Yunkwon; Shin, Soo Jung; Prajapati, Ritu; Shin, Seong Min; Kim, Minjeong; Kim, Hyeon soo; Leem, Seol Hwa; Kim, Tae-Jin; Park, Taesung; Kim, Jwa-Jin; Choi, Jae Sue; Moon, Minho

doi:10.1016/j.biopha.2022.113865

Cited by 10 publications

(1 citation statement)

References 72 publications

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“…Two-and three-dimensional structures of the test compounds and morin were obtained from the PubChem database, and energy minimization and ligand structure conversion to the PDB fle format were performed using Chimera 1.15 (https://www.cgl.ucsf.edu/chimera). For molecular docking purposes, we prepared receptors and ligands using AutoDockTools, whereas to conduct molecular docking, we applied the prepared macromolecules and ligands using AutoDockTools [36]. In the case of the monomer structures of Aβ, we used Autogrid to generate grid parameters centered on the reference ligand and created a grid box of 60 × 60 × 60 Å.…”

Section: Molecular Docking Simulationmentioning

confidence: 99%

Anti-Glycation, Anti-β-Amyloid Aggregation, and Antioxidant Effect of Cassia Seed-Derived Secondary Metabolites

Paudel,

Prajapati,

Lim

et al. 2023

Journal of Food Biochemistry

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Aggregation and non-enzymatic glycation of amyloidogenic peptides, amyloid-beta (Aβ), and insulin are key features of neuropathology. In this study, we evaluate the anti-glycation effect of Cassia seed-derived secondary metabolites on human insulin and bovine serum albumin, as well as their anti-Aβ aggregation and antioxidant effects using in vitro spectrofluorometric method, thioflavin T fluorescence, and peroxynitrite (ONOO‒) scavenging assay. Furthermore, molecular docking simulation was performed to investigate the binding characteristics of test compounds and Aβ42 peptide. Among 38 compounds, anthraquinones 9–12 and 14–18; naphthopyrones 24, 25, 27, and 33–36; and 38 from the naphthalenes and naphthalenic lactone groups showed moderate-to-good inhibition of AGE formation with IC50 values ranging from 7.52 ± 1.19 to 155.86 ± 0.79 µM. Likewise, compounds 5, 24, 15, 16, 27, and 20 showed good inhibition of D-ribose-mediated glycation of human insulin, with an IC50 value range of 46.37 ± 4.06 to 97.69 ± 7.88 µM. In the thioflavin-T assay, compounds 8 and 12 showed promising inhibition of Aβ aggregation, comparable to that of the reference compound morin. Molecular docking simulations confirmed that these active compounds have strong potential to interact with Aβ42 peptides and interrupt their self-assembly and conformational transformation, thereby inhibiting Aβ42 aggregation. In addition, compounds 5, 8, 10, 14, and 35 scavenged ONOO− at low concentrations. Overall, Cassia compounds’ anti-glycation, anti-Aβ aggregation, and antioxidant effects warrant further in vivo studies to evaluate their potential neuroprotective effects against comorbid AD and diabetes.

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Section: Molecular Docking Simulationmentioning

confidence: 99%