Luteolin Could Improve Cognitive Dysfunction by Inhibiting Neuroinflammation

Neurochem Res. 2018 Apr;43(4):806-820. doi: 10.1007/s11064-018-2482-2. Epub 2018 Feb 1.


Neuroinflammation and oxidative stress play an important role in cognition deficit following chronic cerebral hypoperfusion (CCH). Luteolin, a natural flavonoid found in many plants, is known for a variety of pharmacological activities, such as its anti-inflammatory, anti-allergy, urate, anti-tumor, antibacterial, and antiviral effects. To assess whether luteolin could prevent CCH-induced cognitive dysfunction, through its anti-inflammatory and anti-oxidative-stress effects, we used enzyme-linked immunosorbent assays, enzyme activity assays, behavioral methods, immunohistochemistry, and electrophysiology to detect neuroinflammation and oxidative stress, cognition alterations, and long-term potential (LTP), in a bilateral common carotid arteries ligation (2VO) rat model. We demonstrated that CCH increased tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Further, it caused microglia over-activation and astrogliosis, learning and short-term memory dysfunction, and an LTP deficit. Luteolin treatment reversed CCH-induced changes. Specifically, luteolin prevented the increase of TNF-α and IL-1β, IL-6, and MDA, improved the activity of SOD and GPx, inhibited microglia over-activation and astrogliosis (particularly in the hippocampus and cortex), and ameliorated learning and short-term memory dysfunction, and LTP deficit. Thus, our study suggested that luteolin could be a preferable anti-inflammatory agent to protect cognitive function and synaptic plasticity following CCH. Luteolin could also be putative therapeutic candidate for other inflammation-related brain diseases.

Keywords: Chronic cerebral hypoperfusion; Cognition dysfunction; Luteolin; Neuroinflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / metabolism
  • Luteolin / pharmacology
  • Luteolin / therapeutic use*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Luteolin