Liensinine improves cognitive dysfunction behavior via restoring neurotransmitters and microbial remodeling pathway

Cognitive dysfunction (CD) is a clinical syndrome that affects individual cognitive ability seriously. Liensinine could significantly alleviate cognitive impairments in dementia, however, the underlying mechanisms are still unclear. This study investigated the mechanism of liensinine on intervention of CD by metabolomics and 16S rRNA. After administration of liensinine, the CD mice showed a significant decrease in the escape latency and increase in the numbers of crossing the target quadrant and residence times. The levels of Aβ and Tau proteins were decreased, while neurotransmitters were increased. Metabolomics results showed that fecal metabolites were altered significantly, especially increasing the content of carnitine compounds and reducing the levels of 4-hydroxyquinoline, dihydroceramide, and indole-3-carboxaldehyde. Furthermore, liensinine also improved the proliferation of beneficial bacteria (including Bifidobacterium and Akkermansia) and reduced the abundance of harmful bacteria (Helicobacter and Enterorhabdus). The critical mechanism of Liensinine ameliorates cognitive dysfunction may be through the modulation of intestinal flora and metabolic function.