Integration of transcriptomics and network analysis deciphers the mechanisms of baicalein in improving learning and memory impairment in senescence-accelerated mouse prone 8 (SAMP8).

Our previous work suggested that baicalein could delay senescence and improve cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8). Although baicalein has shown therapeutical benefits in improving learning and memory impairment, the exact molecular mechanisms have not been fully understood. In the present work, transcriptomics was integrated with gene network analysis for revealing the potential mechanisms of baicalein in improving learning and memory in SAMP8 mice. The results showed that baicalein regulated fifty hub differently expressed genes (DEGs) that were enriched in eight signaling pathways. Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was especially significant among them, therefore, the DEGs (Gh1, Il5, Il7, Il20rb, Prlr and Socs1) in JAK-STAT signaling pathway were verified by quantitative real-time PCR, and the key proteins (JAK2, p-JAK2, STAT1 and p-STAT1) and related proteins including β-amyloid peptide (Aβ1-42) and receptor for advanced glycation end products (RAGE) were assayed by Western blot and enzyme-linked immunosorbent assay. Our results suggest that baicalein prevented the activation of JAK2/STAT1 signaling pathway and decreased the levels of Aβ1-42 and RAGE in the cortex of SAMP8 mice. Taken together, our study unmasks the mechanism of baicalein on improving learning and memory impairment in SAMP8 mice, which is dependent upon the inhibition of Aβ1-42 and RAGE/JAK2/STAT1 cascade.