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

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.

PeruNPDB: the Peruvian Natural Products Database for in silico drug screening

“…Thus, the concerted effort of experimental NPs research with CADD is continuously increasing; and recently, NPs from the Peruvian native plants Smallanthus sonchilofolius , Lepidium meyenii (40 compounds) 39 , and Uncaria tomentosa (26 compounds) 101 were in silico analyzed for their antiviral activity against SARS-CoV-2. Also, the in silico polypharmaceutical potential of 84 NPs from S. sonchifolius , L. meyenii , Croton lechleri , U. tomentosa , Minthostachys mollis , and Physalis peruvianus was analyzed against Alzheimer’s disease 102 .…”

PeruNPDB: The Peruvian Natural Products Database for in silico drug screening

“…Thus, the concerted effort of experimental NPs research with CADD is continuously increasing; and recently, NPs from the Peruvian native plants Smallanthus sonchilofolius , Lepidium meyenii (40 compounds) [38]; and Uncaria tomentosa (26 compounds) [100] were in silico analyzed for their antiviral activity against SARS-Cov-2. Also, the in silico polypharmaceutical potential of 84 NPs from S. sonchifolius , L. meyenii , Croton lechleri , U. tomentosa , Minthostachys mollis , and Physalis peruvianus was analyzed against Alzheimer’s disease [101].…”

Current Naturopathy to Combat Alzheimer’s Disease

“…Brassicasterol, a 28-carbon sterol, is found in several plant species and is capable of successfully crossing the BBB, which adds to its pharmacological significance for therapeutic administration [ 195 , 196 ]. Brassicasterol has been found to interact with Lys28, Asp23, Val30, His14, Ala211, Ala21and Ile32 residues of Aβ, and Gln351, Lys353, and Ser352 of tau protein forming hydrogen bonds and leading to their inhibition [ 197 ]. Thus, the administration of brassicasterol may serve multipartite functions; first, by directly interacting with tau and Aβ; second, by improving the repertoire of cephalic sterols and third, reduced brassicasterol in CSF may act as a biomarker for the progression of AD [ 195 ].…”