Improvement effects of cyclic peptides from Annona squamosa on cognitive decline in neuroinflammatory mice

Cyclic peptides can resist enzymatic hydrolysis to pass through the intestine barrier, which may reduce the risk of mild cognition decline. But evidence is lacking on whether they work by alleviating neuroinflammation. A cylic peptide from Annona squamosa, Cylic(PIYAG), was biologically evaluated in vivo and in vitro. Cylic(PIYAG) enhanced the spatial memory ability of LPS-induced mice. And treatment with Cylic(PIYAG) markedly reduced the iNOS, MCP-1, TNF-α, and gp91phox expression induced by LPS. Cylic(PIYAG, 0.01, 0.05 and 0.2 μM) could significantly reduce the protein expression level of COX-2 and iNOS (P < 0.05) in BV2 cells. The concentration of Cylic(PIYAG) in blood reached a peak of 3.64 ± 1.22 μg/ml after intragastric administration in 1 h. And fluorescence microscope shows that Cylic(PIYAG) mainly locates and may play an anti-inflammatory role in the cytoplasm of microglia. This study demonstrates that the peptidic can prevent microglia activation, decrease the inflammatory reaction, improve the cognition of LPS-induced mice.

The online version contains supplementary material available at 10.1007/s10068-023-01441-8.