The therapeutic effect of Zhenbao pills on behavioral changes in zebrafish caused by aluminum chloride

Zhenbao pill (ZBP) is a type of traditional Mongolian medicine that contains 241 ingredients such as flavonoids, anthraquinones, triterpenoids, sterols, and Calculus bovis, which are mainly used for treating neurological diseases in clinical practice. In this study, we established an Alzheimer’s disease (AD)-mimetic symptomatic zebrafish model by AlCl3 treatment and investigated the therapeutic effect of ZBP on the AD-mimetic zebrafish model. The results revealed that AlCl3 treatment led to behavioral impairment, induced apoptotic cell (body) in the brain, increased acetylcholinesterase (AChE) activity, and decreased the ACh content in zebrafish. After treatment with ZBP, 16 μg/mL ZBP could alleviate the behavioral disorder of zebrafish larvae. This effect was found superior to the effect of the cholinesterase inhibitor donepezil hydrochloride. The analysis of transcriptomics data revealed that ZBP mainly acted on apoptosis, the p53 signaling pathway, and the enrichment of the AChE-associated pathway. Furthermore, the overexpression of AChE RNA produced similar AD-mimetic disorders, whereas AChE-gene knockdown (AChE-MO) decreased the AChE activity and alleviated the AD-mimetic symptoms. These results suggested that ZBP is a potential cholinergic-enhancing drug, which can be used for the treatment of AD in the future.