Spearmint Extract Containing Rosmarinic Acid Suppresses Amyloid Fibril Formation of Proteins Associated with Dementia.

Kenjirou Ogawa,Aimi Shindo,Yasushi Kawata,Ayumi Ishii,Kunihiro Hongo,Tetsuya Sogon,Tomohiro Mizobata

doi:10.3390/nu12113480

Abstract

Neurological dementias such as Alzheimer’s disease and Lewy body dementia are thought to be caused in part by the formation and deposition of characteristic insoluble fibrils of polypeptides such as amyloid beta (Aβ), Tau, and/or α-synuclein (αSyn). In this context, it is critical to suppress and remove such aggregates in order to prevent and/or delay the progression of dementia in these ailments. In this report, we investigated the effects of spearmint extract (SME) and rosmarinic acid (RA; the major component of SME) on the amyloid fibril formation reactions of αSyn, Aβ, and Tau proteins in vitro. SME or RA was added to soluble samples of each protein and the formation of fibrils was monitored by thioflavin T (ThioT) binding assays and transmission electron microscopy (TEM). We also evaluated whether preformed amyloid fibrils could be dissolved by the addition of RA. Our results reveal for the first time that SME and RA both suppress amyloid fibril formation, and that RA could disassemble preformed fibrils of αSyn, Aβ, and Tau into non-toxic species. Our results suggest that SME and RA may potentially suppress amyloid fibrils implicated in the progression of Alzheimer’s disease and Lewy body dementia in vivo, as well.

Highlights

Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease are often caused by the formation of fibrillar aggregated proteins of amyloid beta (Aβ), Tau, and α-synuclein [1,2,3,4,5,6]
The formation of amyloid fibrils of αSyn, Aβ, and Tau were monitored for 40 h, 12 h, and 25 h, respectively, by utilizing the specific fluorescence that is emitted by fibril bound
Fibrillation of αSyn and Aβ was almost completely inhibited by the addition of spearmint extract (SME) at concentrations that corresponded to a five-fold molar equivalent of rosmarinic acid (RA) relative to the protein monomer

Summary

Introduction

Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease are often caused by the formation of fibrillar aggregated proteins (amyloid fibrils) of amyloid beta (Aβ), Tau (identified in Alzheimer’s disease patients), and α-synuclein (αSyn; identified in cases of Lewy body dementia and Parkinson’s disease) [1,2,3,4,5,6]. Nutrients 2020, 12, 3480 various biological and neurochemical symptoms such as astrogliosis, neuronal dystrophy, and decline in acetylcholine levels such [9]. It is important to suppress aggregation of these and neurochemical symptoms as astrogliosis, neuronal dystrophy, and the decline in acetylcholine proteins with to prevent thesethe symptoms. It dementia is important to suppress aggregation of these proteins associated with Spearmint (Mentha spicata) is a prominent member of the Labiatae family, which is noted for its dementia to prevent these symptoms. HighSpearmint rosmarinic(Mentha acid (RA) content [10]. (the chemical structure of (R)-(+)-rosmarinic is shown in spicata) is a prominent member of the Labiatae family, whichacid is noted for its Figure. A significant in RA wasstructure achievedofin cultivars produced inisbreeding high rosmarinic acid (RA) increase content [10]

Methods

Results

Discussion

Conclusion