In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer's Disease.

Luis Daniel Goyzueta-Mamani,Haruna Luz Barazorda-Ccahuana,Miguel Angel Chávez-Fumagalli,Jorge Alberto Aguilar-Pineda,Christian Lacks Lino Cardenas,Karla Lucia F Alvarez,Karin Jannet Vera-Lopez

doi:10.3390/molecules27030918

Luis Daniel Goyzueta-Mamani, Haruna Luz Barazorda-Ccahuana + Show 5 more

Open Access

https://doi.org/10.3390/molecules27030918

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Abstract

Background: Despite research on the molecular bases of Alzheimer’s disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers. Methods: We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials. Results: Our results demonstrated the increased bioactivity of three plants’ metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau. Conclusions: This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.

Highlights

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by the progressive manifestations of disturbances on rational thinking, memory loss, cognitive decline, and mood changes [1,2,3]
In this work, based on an in silico and computer-aided drug screening, we aimed to show the therapeutic potential of three metabolites derived from Peruvian plants for the possible treatment of patients with Alzheimer’s disease
The natural compounds literature from Peruvian plants were retrieved from the PubMed database

Summary

Introduction

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by the progressive manifestations of disturbances on rational thinking, memory loss, cognitive decline, and mood changes [1,2,3] These clinical manifestations are consequences of the formation of neurofibrillary tangles, senile plaques, glial cell activation, and cerebrovascular dysregulation [4]. The AT1R, located on neurons, astrocytes, and microglia [17], has the function of NADPH oxidase complex activation, which leads to superoxide formation, vasoconstriction, proinflammatory, and pro-oxidative effects [15,16]. For this reason, research on AT1R blockers (ARBs) has increased in the last decade due to the findings on the increment of ACE activity in AD patients.

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