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 bene cial 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 rst veri ed for their ability to diminish Aβ42 brillation 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 brillation 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.

Protective Effects of Sal B on Oxidative Stress-Induced Aging by Regulating the Keap1/Nrf2 Signaling Pathway in Zebrafish

“…lecules 2021, 26, x FOR PEER REVIEW 3 of 17 loss [33]. Florence Hui Ping Tan also demonstrated that Danshen water extract (DWE) and its components (Sal A and Sal B) may have therapeutic potential for AD patients and possibly other forms of brain diseases [34]. However, the result and mechanism of action of Sal B on cell and embryo aging has not been clearly expounded.…”

“…Zheng Zhiwei demonstrated that Sal B exhibited significant effect on protection against aminoglycoside antibiotics and cisplatin-induced ototoxicity by suppressing the production of ROS and mitochondrial apoptotic pathway, indicating that Sal B could be a preventive or therapeutic agent in the treatment of ototoxic insult-induced hearing loss [33]. Florence Hui Ping Tan also demonstrated that Danshen water extract (DWE) and its components (Sal A and Sal B) may have therapeutic potential for AD patients and possibly other forms of brain diseases [34]. However, the result and mechanism of action of Sal B on cell and embryo aging has not been clearly expounded.…”

Behavioural effects and RNA-seq analysis of Aβ42 mediated toxicity in a Drosophila Alzheimer’s disease model

“…Most importantly, the D. melanogaster is able to recapitulate many age-dependent behavioural aspects such as memory and motor capacities [8]. Recently, the D. melanogaster has been extremely useful in AD therapeutics discovery such as probiotic studies [9,10] and polyphenol testing [11,12]. Although D. melanogaster has been proven to be an ideal model for AD, transcriptome research on the Drosophila AD model is limited.…”