IMPROVEMENT OF COGNITIVE IMPAIRMENT BY MYRICETIN IN AGING MICE

ZHANG Xiao-yan; XIA Shu-fang; CHEN Xiao

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (4) : 365-371.

ORIGINAL ARTICLES

ZHANG Xiao-yan¹, XIA Shu-fang¹, CHEN Xiao²

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Abstract

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.

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cognitive impairment / myricetin / nlrp3 / inflammation / aging

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ZHANG Xiao-yan, XIA Shu-fang, CHEN Xiao. IMPROVEMENT OF COGNITIVE IMPAIRMENT BY MYRICETIN IN AGING MICE[J]. Acta Nutrimenta Sinica. 2024, 46(4): 365-371

References

[1] Roth GA, Abate D, Abate KH, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2018, 392: 1736–1788.
[2] Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment[J]. Lancet, 2006, 367: 1262–1270.
[3] Deng Y, Zhao S, Cheng G, et al. The Prevalence of Mild Cognitive Impairment among Chinese people: a meta-analysis[J]. Neuroepidemiology, 2021, 55: 79–91.
[4] Mitchell AJ, Shiri-Feshki M.Rate of progression of mild cognitive impairment to dementia: meta-analysis of 41 robust inception cohort studies[J]. Acta Psychiatr Scand, 2009, 119: 252–265.
[5] Franceschi C, Garagnani P, Parini P, et al. Inflammaging: a new immune-metabolic viewpoint for age-related diseases[J]. Nat Rev Endocrinol, 2018, 14: 576–590.
[6] Gorelick PB.Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials[J]. Ann NY Acad Sci, 2010, 207: 155–162.
[7] Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β[J]. Nat Immunol, 2008, 9: 857–865.
[8] Scarmeas N, Anastasiou CA, Yannakoulia M.Nutrition and prevention of cognitive impairment[J]. Lancet Neurol, 2018, 17: 1006–1015.
[9] Kesse-Guyot E, Fezeu L, Andreeva VA, et al. Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later[J]. J Nutr, 2012, 142: 76–83.
[10] Lei Y, Chen J, Zhang W, et al. In vivo investigation on the potential of galangin, kaempferol and myricetin for protection of d-galactose-induced cognitive impairment[J]. Food Chem, 2012, 135: 2702–2707.
[11] Chen H, Lin H, Xie S, et al. Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination[J]. Toxicol Appl Pharmacol, 2019, 365: 19–29.
[12] Feng X, Hu J, Zhan F, et al. MicroRNA-138-5p regulates hippocampal neuroinflammation and cognitive impairment by NLRP3/Caspase-1 signaling pathway in rats[J]. J Inflamm Res, 2021, 14: 1125–1143.
[13] Todorova V, Blokland A.Mitochondria and synaptic plasticity in the mature and aging nervous system[J]. Curr Neuropharmacol, 2017, 15: 166–173.
[14] Sparkman NL, Buchanan JB, Heyen JR, et al. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers[J]. J Neurosci, 2006, 26: 10709–10716.
[15] Gemma C., Bickford PC.Interleukin-1β and caspase-1: players in the regulation of age-related cognitive dysfunction[J]. Rev Neurosci, 2007, 18: 137–148.
[16] Haider S, Liaquat L, Shahzad S, et al. A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process[J]. Life Sci, 2015, 124: 110–119.
[17] Walsh JG, Muruve DA, Power C.Inflammasomes in the CNS[J]. Nat Rev Neurosci, 2014, 15: 84–97.
[18] Zhang X, Xu A, Lv J, et al. Development of small molecule inhibitors targeting NLRP3 inflammasome pathway for inflammatory diseases[J]. Eur J Med Chem, 2020, 185: 111822.
[19] Ising C, Venegas C, Zhang S, et al. NLRP3 inflammasome activation drives tau pathology[J]. Nature, 2019, 575: 669-673.
[20] Dempsey C, Rubio Araiz A, Bryson KJ, et al. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice[J]. Brain Behav Immun, 2017, 61: 306–316.
[21] Han X, Sun S, Sun Y, et al. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease[J]. Autophagy, 2019, 15: 1860–1881.
[22] Pluta R, Januszewski S, Czuczwar SJ.Myricetin as a promising molecule for the treatment of post-ischemic brain neurodegeneration[J]. Nutrients, 2021, 13: 342.
[23] Hou W, Hu S, Su Z, et al. Myricetin attenuates LPS-induced inflammation in RAW 264.7 macrophages and mouse models[J]. Future Med Chem, 2018, 10: 2253–2264.
[24] Adlakha YK, Saini N.Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128[J]. Mol Cancer, 2014, 13: 33.
[25] Schratt GM, Tuebing F, Nigh EA, et al. A brain-specific microRNA regulates dendritic spine development[J]. Nature, 2006, 439: 283–289.
[26] Kou X, Liu X, Chen X, et al. Ampelopsin attenuates brain aging of D-gal-induced rats through miR-34a-mediated SIRT1/mTOR signal pathway[J]. Oncotarget, 2016, 7: 74484–74495.
[27] Zhou Y, Lu M, Du R, et al. MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson's disease[J]. Mol Neurodegener, 2016, 11: 28.
[28] Li D, Yang H, Ma J, et al. MicroRNA-30e regulates neuroinflammation in MPTP model of Parkinson's disease by targeting Nlrp3[J]. Hum Cell, 2018, 31: 106–115.
[29] Huang WQ, Wei P, Lin RQ, et al. Protective effects of microrna-22 against endothelial cell injury by targeting NLRP3 through suppression of the inflammasome signaling pathway in a rat model of coronary heart disease[J]. Cell Physiol Biochem, 2017, 43: 1346–1358.