Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease

Abstract

Alzheimer’s disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-β plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents β-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide 306VQIVYK311 involved in fibrillization and β sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid.

Protective effects of Avena sativa against oxidative stress‐induced kidney damage resulting from an estrogen deficiency in ovariectomized Swiss mice model

“…In addition, amentoflavone and myricetin are interesting flavonoids known by their powerful antioxidant and free radical‐scavenging activities. Likewise, rosmarinic acid has been reported to have anti‐oxidant and neuroprotective effects (Cornejo et al, 2017).…”

Nonpharmacological treatment options for Alzheimer’s disease: from animal testing to clinical studies

“…Reducing Aβ1-42 accumulation and levels of APP, inhibiting BACE1 activity (Liu et al, 2017) Curcumin Activating neuronal nitric oxide pathway Caffeic acid Blocking Aβ formation and aggregation (Habtemariam, 2016) Epigallocatechin Modulating the enzymes involved in APP processing and reducing the formation of Aβ (Rezai-Zadeh, 2005) Ferulic acid Exerting antiinflammatory actions (Ghosh et al, 2017) Gallic acid Preventing fibril formation by Aβ peptide (Liu et al, 2013) Genistein Modulating neuroinflammation, Aβ deposition, and tau hyperphosphorylation (Park et al, 2016) Hesperidin Exhibiting high-affinity BACE1 inhibitor, preventing Aβ fibril formation (Chakraborty et al, 2016) Honokiol Modulating excitotoxicity associated with the blockade of glutamate receptors and reducing neuroinflammation (Talarek et al, 2017) Icariin Preventing Aβ1-42 aggregation (Liu et al, 2015) Leucomicin Preventing Aβ1-42 induced oxidative stress (Türkez, 2018) Lycopene Inhibiting NF-κB activity and regulating neuroinflammatory cytokines (Sachdeva and Chopra, 2015) Naringenin Alleviating Aβ-induced impairments, lipid peroxidation, and apoptosis via the estrogenic pathway. (Ghofrani et al, 2015) Nobiletin Reducing Aβ plaques, NFTs, and cognitive impairments (Nakajima et al, 2015) Oleuropein Counteracting amyloid-β peptide and tau aggregation (Martorell et al, 2016) Quercetin Minimizing Aβ1-40 and Aβ1-42 amounts, decreasing BACE1-mediated cleavage of APP (Sabogal-Guáqueta et al, 2015) Rosmarinic acid Preventing Aβ-sheet assembly (Cornejo et al, 2017) Resveratrol Promoting the removal of Aβ peptides and antiinflammatory content (Braidy et al, 2016) Rutin Inhibiting Aβ aggregation, supporting antioxidant SOD, CAT, and GSH-Px enzyme activities (Yu et al, 2015) Sulforaphane Reducing cholinergic neuron loss (Zhang et al, 2014) Tangeretin Alleviating cholinergic deficits, reducing Aβ accumulation, inhibiting tau hyperphosphorylation and increasing NEP levels (Braidy et al, 2017a) Tannic acid…”

Properties and use of rosemary (Rosmarinus officinalis L.)

“…Cornejo et al [51] evaluated epiisorosmanol, rosmanol, carnosol, carnosic and rosmarinic acid isolated from rosemary. They were observed to play a part in inhibiting structural neurodegenerative changes in the course of brain diseases caused by the aggregation of various undesirable compounds, in this case, tau proteins.…”