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Neurotoxicity Research

, Volume 36, Issue 4, pp 844–858 | Cite as

Protective Effect of Semisynthetic and Natural Flavonoid on Aged Rat Microglia–enriched Cultures

  • Nataša Mrvová
  • Martin Škandík
  • Štefan Bezek
  • Lucia RačkováEmail author
Original Article

Abstract

The ROS-mediated lysosomal dysfunction and coinciding deterioration of mitochondrial function are thought to be the prominent mechanisms responsible for aging. Microglia, the resident macrophages in the central nervous system, were postulated to belong to the major targets vulnerable to these detrimental processes, acting as principal drivers in brain aging. The present study investigated the potential protective effect of the semisynthetic flavonoid 3′-O-(3-chloropivaloyl) quercetin (CPQ) and quercetin (Q) on microglia-enriched mixed brain cultures (MBCs) established from aged Wistar rats. Both flavonoids tested suppressed the development of lipofuscin-related autofluorescence in aged cells. Further ensuing protective effects included reduction of protein oxidation markers in aged cells. Moreover, unlike Q, CPQ significantly suppressed sensitivity of aged cells to stimulation of superoxide burst. Other activation markers, cellular hypertrophy and isolectin B4 binding, were also downregulated by treatment with both CPQ and Q. In conclusion, results of our study suggest that both flavonoids tested may protect microglia with a quite comparable efficacy against aging-related accumulated alterations. The protective mechanism can include interference with the ROS-mediated vicious cycles involving lysosomal dysfunction. Nevertheless, the lipophilized quercetin, CPQ, a compound with proposed enhanced biological availability compared to parent molecule, can represent an agent potentially useful for new effective pharmaceutical intervention against brain aging, overcoming the limitations of clinical applicability of quercetin.

Keywords

Microglia Aging Flavonoids Lipofuscin Mitochondria ROS 

Notes

Acknowledgments

The study was supported by VEGA 2/0041/17, VEGA 2/0031/12, VEGA 2/0029/16, APVV-18-0336, APVV-15-0308. The work was supported by The Agency of the Ministry of Education of the Slovak Republic for the Structural Funds of EU, OP R&D of ERDF as a part of the Project: “Evaluation of natural substances and their selection for prevention and treatment of lifestyle diseases” (ITMS 26240220040).

Compliance with Ethical Standards

The study was performed in compliance with the Principles of Laboratory Animal Care and was approved by the institutional ethics committee and by the State Veterinary and Food Administration of the Slovak Republic (Act No. Ro-2590/11-221).

Conflict of Interest

The authors declare that there is no conflict of interest.

Supplementary material

12640_2019_71_MOESM1_ESM.pdf (597 kb)
Online Resource 1 (PDF 596 kb)
12640_2019_71_MOESM2_ESM.pdf (104 kb)
Online Resource 2 (PDF 104 kb)

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Authors and Affiliations

  1. 1.Center of Experimental Medicine, Institute of Experimental Pharmacology and ToxicologySlovak Academy of SciencesBratislavaSlovak Republic

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