Alleviatory effects of Danshen, Salvianolic acid A and Salvianolic acid B on PC12 neuronal cells and Drosophila melanogaster model of Alzheimer's disease.

Abstract

Alzheimers disease (AD) is the most common form of neurodegenerative disorder worldwide. Its pathogenesis involves the hallmark aggregation of amyloid-beta (A{beta}). Of all the A{beta} oligomers formed in the brain, A{beta}42 has been found to be the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. With the ability to utilize various genetic manipulations, Drosophila melanogaster is ideal in analysing not only cellular characteristics, but also physiological and behavioural traits of human neurodegenerative diseases. Danshen water extract (DWE), obtained from the root of Salvia miltiorrhiza Bunge, was found to have a vast array of beneficial properties. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to ameliorate A{beta}42s effects. DWE, SalA and SalB were confirmed to be able to reduce fibrillation of A{beta}42. As A{beta}42 causes neurodegeneration on neurons, DWE, SalA and SalB were tested on A{beta}42-treated PC12 neuronal cells and were shown to increase cell viability. DWE and its components were then tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. When human A{beta}42 was expressed, the Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila. In conclusion, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.