Updated project metadata. The prevalence of neurodegenerative diseases is rapidly increasing with the aging trend of global populations, severely threatening human health and burdening society. However, to date, there is no effective treatment able to halt the progression or cure the diseases. Here, We aim to develop effective treatments for neurodegenerative diseases from novel sources by evaluating their neuroprotective activity and investigating the working mechanism. Primary screening on glutamate-induced excitotoxicity was assessed by MTT assay. The combination of transcriptomics and proteomics analysis were used to identify the targets of pterosin B. The key pathways were enriched by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The core targets were analyzed by protein-protein interactions network by STRING. The mRNA expressions and protein expressions were evaluated using qPCR and western blot, respectively.