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The Protective Effect of Amber Extract on Neurodegenerative Diseases

羅, 月寧 筑波大学 DOI:10.15068/0002005492

2022.11.18

概要

1. Background and Objective
　The population in the world was over 7.8 billion in 2019. Among them, the population aged 60 years and over is expected to exceed 1 billion in 2019 and 2.1 billion by 2050 (World population ageing 2019). Currently, in some countries, like Japan, Switzerland, and South Korea, the average life expectancy is over 80 years old. Ageing had become a fundamental to some diseases, such as hearing loss, cataracts, diabetes, neurodegenerative diseases, etc. Unlike other diseases, almost no effective treatments or drugs are available for neurodegenerative diseases nowadays. In previous studies, some traditional Chinese medicinal plants, have been reported had effect on neurodegenerative diseases in vivo and vitro.
　Here, I focused on amber, which is a fossil plant resin. Amber is commonly used as jewelry and decorative object. However, the medicinal properties of amber, such as mental stability, stoppage of bleeding, wound healing, and diuresis, have been mentioned in the book from thousand year ago in China. Furthermore, in previous studies, amber extract also has anti-allergic effects and melanin pigment reduction. In our laboratory, we had clarified that amber extract has physiological effects such as anti-inflammatory and reduction of fat accumulation. Although amber has been used to induce mental stability in humans for thousands of years, no research evidence is available to date. Therefore, this study aimed to investigate the protective effects of amber extract on neurodegenerative diseases.
　In this study I focused on Alzheimer's disease and Parkinson's disease. Alzheimer's disease (AD), an irreversible and progressive brain disorder, is characterized by a slow impairment of memory and thinking abilities. Eventually, the patients lose their ability to perform basic daily tasks. Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease after Alzheimer’s disease and is characterized by movement disorders such as resting tremor, bradykinesia, rigidity, and postural instability. Both of these diseases have a strong relative with ageing.
　Therefore, in this study I used amyloid-β to establish an Alzheimer's disease model and used 6-OHDA to establish a Parkinson's disease model and aimed to elucidate the protective effects of amber extracts and the mechanism.

2. Results and discussion
2-1. The protect effect on Alzheimer's disease model in vitro
　I used amyloid-β (1-42) and SH-SY5Y cell to establish an Alzheimer's disease model. The result show that cell viability was significantly increased in the amber extract group than in the amyloid-β (1-42) group. Thus, it can be concluded that amber extract protected the cells from amyloid-β (1-42)-induced cytotoxicity. Then, apoptosis assay used to analyze cell apoptosis and cleaved caspase 3 protein level has also been detected. The increased apoptosis cell and cleaved caspase 3 due to amyloid-β (1-42) were decreased by amber extract. This is suggested that amber extract can protect cell from amyloid-β (1- 42)-induced cell apoptosis. Then, anti-apoptosis and apoptosis relative gene, Bcl-2, and Bax mRNA levels were measured. The expression of Bcl-2 decreased in amyloid-β (1- 42) group and increased in amber extract group compare with amyloid-β (1-42) group. However, the expression of Bax showed no significant difference among the groups. Additionally, the mRNA ratio of Bax/Bcl2 was significantly increased in the amyloid-β (1-42) group, and it was decreased in amber extract group. Then, ROS generation was measured. ROS generation was increased in amyloid-β (1-42) group. However, the increased ROS were decreased in amber extract group. The results of ROS, Bcl-2, and Bax mRNA levels demonstrated that amber extract reduces apoptosis via the ROS- mediated mitochondrial pathway.
　The BACE1 protein level increased in the amyloid-β (1-42) group and decreased in amber extract group. These results suggest that amber extract can downregulate amyloid- β (1-42)-induced BACE1 expression. In addition, autophagy relative proteins Beclin1 and LC3 have also been measured, amyloid-β (1-42) increased the protein levels of Beclin-1 and LC3 II. The protein levels of Beclin-1 and LC3 II were higher in the amber extract group than in the amyloid-β (1-42) group. Furthermore, the protein ratio of LC3 II/LC3 I show no different between amyloid-β (1-42) group and control group but increased in the amber extract group. It is suggested that amber extract can promote autophagy. These results revealed that amber extract may protect neuronal cells from the toxicity of amyloid β.

2-2. The protect effect on Parkinson's disease model in vitro
　I used 6-OHDA and SH-SY5Y cell to establish a Parkinson's disease model. The result of cell viability and apoptosis show that amber extract reduced 6OHDA-induced cell apoptosis. Then, ROS generation and phosphorylated ERK protein levels were measured. ROS generation and phosphorylated ERK protein levels were increased in 6-OHDA group. However, the increased ROS generation and phosphorylated ERK protein levels were decreased in amber extract group. These results suggest that amber extract regulates cell death via the ROS and ERK pathways.
　Autophagy relative proteins Beclin1 and LC3 have also been measured. 6-OHDA decreased the protein levels of Beclin-1, but no effect on LC3 II. However, the protein levels of Beclin-1 and LC3 II were increased in the amber extract group. Furthermore, the protein ratio of LC3 II/LC3 I show no different between 6-OHDA group and control group but increased in the amber extract group. Which suggest that amber extract can promote autophagy. These results revealed that amber extract may protect neuronal cells from the toxicity of 6-OHDA.
　These results indicate that amber can be potentially used as a novel treatment and prophylactic candidate for neurodegenerative diseases.

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