Novel Perspective on Alzheimer’s Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid β

Abstract

Alzheimer’s disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue. The major hallmark of Alzheimer’s disease is the presence of toxic aggregated species in the brain, impaired metal homeostasis, and high levels of oxidative stress. Rosmarinic acid is a well-known potent antioxidant molecule, the efficacy of which has been proved both in vitro and in vivo. In this study, we investigated the possible role played by rosmarinic acid as a mediator of the copper(II)-induced neurotoxicity. Several spectroscopic techniques and biological assays were applied to characterize the metal complexes and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu(II) complex. Our data indicate that rosmarinic acid is able to interfere with the interaction between amyloid β and Cu(II) by forming an original ternary association.

Spectroscopic, Electrochemical, and Biological Assays of Copper-Binding Molecules for Screening of Different Drugs and Plant Extracts against Neurodegenerative Disorders

“…The authors concluded that curcumin can simultaneously bind to Cu 2+ and β-amyloid, forming a ternary system. Recently, similar results were also obtained by Kola and co-workers using rosmarinic acid, and the system was characterized via different spectroscopic techniques. Cytotoxic studies revealed that the copper­(II) complex was able to reduce the percentage of cellular viability on NIH3T3 fibroblasts cells.…”

Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

“…Previously, RA showed several pharmacological properties, including anti‐inflammatory (K. Jiang et al, 2018), antioxidant (Luft et al, 2019), antitumor (Han, Ma, Zhao, Feng, & Zheng, 2019; Messeha, Zarmouh, Asiri, & Soliman, 2020; L. Wang, Yang, Wang, Shi, & Li, 2019), and photoprotection (Sánchez‐Campillo et al, 2009). Furthermore, RA may exert neuroprotective action in the CNS in cases of neurodegeneration (Bhatt, Singh, Prakash, & Mishra, 2015; Hase et al, 2019; Kola, Hecel, Lamponi, & Valensin, 2020; Shan et al, 2015) and mood disorders, including depression and anxiety (Ghasemzadeh Rahbardar & Hosseinzadeh, 2020; Lin et al, 2015). Earlier, using the chronic unpredictable stress model, it was suggested that the antidepressant‐like effect of RA could be related to increase of hippocampal astrocyte BDNF expression through modulation of the extracellular‐regulated kinase (ERK) phosphorylation stress (Jin, Liu, Yang, Zhang, & Miao, 2013).…”

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

“…Furthermore, RA was able to suppress Aβ accumulation via dopamine-signaling pathway enhancement [182] and reduce inflammation by downregulating JNK signaling pathway [183]. Recent findings showed that RA interferes with Cu(II)-Aβ complex and forms original ternary association that modifies Aβ reactivity in terms of aggregation and ROS generation [184]. As expected, RA treatment promoted cognitive improvement and neuroprotection against Aβ25- 35 [185], Aβ42 [186,187], and scopolamine [188] induced toxicity in rat model of AD.…”