Structure–activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties

Taguchi, Riho; Hatayama, Koki; Takahashi, Tomohito; Hayashi, Takafumi; Sato, Yuki; Sato, Daisuke; Ohta, Kiminori; Nakano, Hiroto; Seki, Chigusa; Endo, Yasuyuki; Tokuraku, Kiyotaka; Uwai, Koji

doi:10.1016/j.ejmech.2017.07.026

Cited by 60 publications

(37 citation statements)

References 26 publications

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“…Figure 1 B plots the amount of aggregates estimated from the SD of the brightness of each pixel of a fluorescence microscope image [ 28 , 36 ]. Under similar conditions, Aβ began to aggregate at around 5 h [ 34 ], suggesting that the lag time of SAA aggregation is shorter than that of Aβ. Similar to Aβ, tau and α-synuclein [ 36 ], 3D images of SAA aggregates could be obtained by confocal laser microscopy.…”

Section: Resultsmentioning

confidence: 99%

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Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice

Lin

Watanabe

Kuragano

et al. 2020

IJMS

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Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis, although the underlying aggregation mechanism has not been elucidated. Since SAA aggregation is a key step in this pathogenesis, inhibitors are useful to prevent and treat AA amyloidosis, serving as tools to investigate the pathogenic mechanism. In this study, we showed that rosmarinic acid (RA), which is a well-known inhibitor of the aggregation of amyloid β (Aβ), displayed inhibitory activity against SAA aggregation in vitro using a microliter-scale high-throughput screening (MSHTS) system with quantum-dot nanoprobes. Therefore, we evaluated the amyloid aggregation inhibitory activity of blood and the deposition of SAA in organs by feeding mice with Melissa officinalis extract (ME) containing RA as an active substance. Interestingly, the inhibitory activity of ME-fed mice sera for SAA and Aβ aggregation, measured with the MSHTS system, was higher than that of the control group. The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group, suggesting that the SAA aggregation inhibitory activity of serum is associated with SAA deposition. These results suggest that dietary intake of RA-containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs. This study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor comprehensive activity of metabolized foods adsorbed by blood.

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Section: Resultsmentioning

confidence: 99%

“…It was subsequently reported that Aβ plaque deposition in RA-fed mice was reduced [ 33 ]. RA also shows high antioxidant activity, and antioxidants with a catechol moiety inhibited the aggregation of various amyloid proteins such as Aβ, tau, and α-synuclein [ 34 , 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice

Lin

Watanabe

Kuragano

et al. 2020

IJMS

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“…As previously described [24], an inhibitory compound, rosmarinic acid (RA), was extracted from Satureja hortensis (summer savory), a spice belonging to the Lamiaceae family. RA has high Aβ aggregation inhibition activity, antioxidant properties, and can also inhibit xanthine oxidase [26]. An aggregation inhibitory test of these proteins using RA was performed, noting that RA inhibited the aggregation of Aβ but not tau.…”

Section: Introductionmentioning

confidence: 99%

Real-Time 3D Imaging and Inhibition Analysis of Various Amyloid Aggregations Using Quantum Dots

Lin

Galaqin

Tainaka

et al. 2020

IJMS

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Amyloidosis refers to aggregates of protein that accumulate and are deposited as amyloid fibrils into plaques. When these are detected in organs, they are the main hallmark of Alzheimer’s disease, Parkinson’s disease, and other related diseases. Recent medical advances have shown that many precursors and proteins can induce amyloidosis even though the mechanism of amyloid aggregation and the relationship of these proteins to amyloidosis remains mostly unclear. In this study, we report the real-time 3D-imaging and inhibition analysis of amyloid β (Aβ), tau, and α-synuclein aggregation utilizing the affinity between quantum dots (QD) and amyloid aggregates. We successfully visualized these amyloid aggregations in real-time using fluorescence microscopy and confocal microscopy simply by adding commercially available QD. The observation by transmission electron microscopy (TEM) showed that QD particles bound to all amyloid fibrils. The 3D-imaging with QD revealed differences between amyloid aggregates composed of different amyloid peptides that could not be detected by TEM. We were also able to quantify the inhibition activities of these proteins by rosmarinic acid, which has high activity for Aβ aggregation, from fluorescence micrographs as half-maximal effective concentrations. These imaging techniques with QD serve as quick, easy, and powerful tools to understand amyloidosis and to discover drugs for therapies.

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“…Several in vitro and animal studies have shown the promise of RA in AD therapy. The experiment by Taguchi et al [ 77 ] using docking simulation and direct binding studies investigated the structural features of RA that allowed it to directly interact with Aβ 1–42 . They have shown that the catechol functional group on the caffeic acid side is an important structural feature for binding.…”

Section: Rosmarinus Acid (Ra) In Admentioning

confidence: 99%

“…One critical structural feature for these compounds both in inhibition of Aβ aggregation and ROS-mediated toxicity is the catechol functional moiety that comes in these compounds in good number ( Figure 2 ). The association between this functional group and anti-AD effects has been established in RA and analogues [ 77 ]. We have also shown that such functional group in phenolic acids as well as in the flavonoids skeleton are optimized for numerous pharmacological effects linked to ROS, metal ions chelation and enzyme inhibition [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ].…”

Section: Summary Of Molecular Mechanisms That Attribute To the Demmentioning

confidence: 99%

Molecular Pharmacology of Rosmarinic and Salvianolic Acids: Potential Seeds for Alzheimer’s and Vascular Dementia Drugs

Habtemariam

2018

IJMS

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Both caffeic acid and 3,4-dihydroxyphenyllactic acid (danshensu) are synthesized through two distinct routs of the shikimic acid biosynthesis pathway. In many plants, especially the rosemary and sage family of Lamiaceae, these two compounds are joined through an ester linkage to form rosmarinic acid (RA). A further structural diversity of RA derivatives in some plants such as Salvia miltiorrhiza Bunge is a form of RA dimer, salvianolic acid-B (SA-B), that further give rise to diverse salvianolic acid derivatives. This review provides a comprehensive perspective on the chemistry and pharmacology of these compounds related to their potential therapeutic applications to dementia. The two common causes of dementia, Alzheimer’s disease (AD) and stroke, are employed to scrutinize the effects of these compounds in vitro and in animal models of dementia. Key pharmacological mechanisms beyond the common antioxidant and anti-inflammatory effects of polyphenols are highlighted with emphasis given to amyloid beta (Aβ) pathologies among others and neuronal regeneration from stem cells.

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Structure–activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties

Cited by 60 publications

References 26 publications

Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice

Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice

Real-Time 3D Imaging and Inhibition Analysis of Various Amyloid Aggregations Using Quantum Dots

Molecular Pharmacology of Rosmarinic and Salvianolic Acids: Potential Seeds for Alzheimer’s and Vascular Dementia Drugs

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