Alleviatory Effects of Danshen, Salvianolic Acid A and Salvianolic Acid B on Pc12 Neuronal Cells and Drosophila Melanogaster Model of Alzheimer’s Disease

Abstract

Background: Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder worldwide. Its pathogenesis involves the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 has been found to be the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. 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 attenuate Aβ42’s toxic effects.Methods: The compounds were first verified for their ability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells as well as the Drosophila melanogaster model organism. Results: DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. When human Aβ42 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. Conclusion: Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.Trial Registration: Not applicable