Salvianolic acids modulate lifespan and gut microbiota composition in amyloid-β-expressing Drosophila melanogaster

Alzheimer's disease (AD), a form of neurodegenerative disorder characterized by the accumulation of amyloid-beta (A beta), hyperphosphorylated Tau, and neuroinflammation. The increasing population affected by AD urges for the development of effective treatments. The correlation between AD and gut microbiome remains underexplored, potentially providing a better understanding of the disease. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B) are the active components extracted from Salvia miltiorrhiza (Danshen), and their antioxidant, anti-inflammation and A beta inhibition activities were shown previously. In this study, these compounds were used to investigate their effects on A beta toxicity, using Drosophila melanogaster expressing human A beta 42 as the model organism, by examining their lifespan and changes in gut bacterial communities. The study used two batches of flies, reared on food with or without methylparaben (MP) supplementation to evaluate the influence of MP on this animal model during pharmacological studies. MP is a common antimicrobial agent used in flies' food. The treatment of Sal A prolonged the lifespan of A beta-expressing flies reared on MP-supplemented food significantly (P < 0.001), but not those without MP. The lifespan of Sal B-treated flies did not show a significant difference compared to untreated flies for both groups reared on food with and without MP. Sal A-treated flies in the presence of MP exhibited a lower abundance of Corynebacterium and Enterococcus than the untreated flies, while Lactiplantibacillus was the most dominant taxa. Urea cycle was predicted to be predominant in this group compared to the untreated group. The control group, A beta-expressing flies treated with Sal A and Sal B on MP-supplemented food had improved lifespan compared to their respective groups reared on food without MP, while untreated A beta-expressing flies was the exception. The gut microbiota composition of flies reared on MP-supplemented food was also significantly different from those without MP (P < 0.001).