Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments

Neurotox Res. 2021 Dec;39(6):1800-1811. doi: 10.1007/s12640-021-00426-x. Epub 2021 Oct 16.

Abstract

Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae, is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.

Keywords: Cognitive impairment; Inflammatory cytokines; Lipopolysaccharide; Luteolin; Neuroinflammation.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Luteolin / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Morris Water Maze Test
  • Neuroinflammatory Diseases / complications
  • Neuroinflammatory Diseases / drug therapy*

Substances

  • Luteolin