IMPROVEMENT OF COGNITIVE IMPAIRMENT BY MYRICETIN IN AGING MICE
Objective To explore the effects of myricetin on cognitive impairment and potential mechanism in D-galactose-induced aging mice.Methods Thirty-six male C57BL/6J mice aged 5 weeks were randomly divided into three groups:control(Con)group,D-galactose-induced aging group(D-gala,150 mg/kg),myricetin intervention on D-galactose-induced aging group(D-gala+Myr,100 mg/kg myricetin).Aging was induced by D-galactose and myricetin was simultaneously used as the intervention.Eight weeks later,Morris water maze test was conducted to assess the learning and memory ability,which was followed by whole brain histology analysis,measurement of hippocampal NLRP3 and Caspase-1 expressions,as well as the inflammatory markers(IL-1β and IL-18 levels).Additionally,the expression of microRNAs that targeted on NLRP3 was also determined.Results Myricetin significantly decreased escape latency which was increased by D-galactose,and increased the time spent in the target quadrant.Myricetin treatment also resulted in well-arranged and increasing number of neurons in hippocampal CA1,CA3 and DG regions.Myricetin remarkably reversed the hippocampal BDNF decline induced by D-galactose,significantly up-regulated miR-7,miR-138-5p and miR-30e expressions and inhibited the expression of their target gene NLRP3 and subsequent cleaved caspase-1(p10),decreased IL-1β,IL-18 and TNF-α levels.Conclusion Myricetin can regulate the expressions of miRs that targets on NLRP3,inhibit the activation of NLRP3/Caspase-1 signaling pathway and hippocampal inflammation,and ultimately improve cognitive impairment.[ACTA NUTRIMENTA SINICA,2024,46(4):365-371]