Neurochemical Research

, Volume 43, Issue 4, pp 806–820 | Cite as

Luteolin Could Improve Cognitive Dysfunction by Inhibiting Neuroinflammation

  • Zhao-Hui Yao
  • Xiao-li Yao
  • Yong Zhang
  • Shao-feng Zhang
  • Ji-chang Hu
Original Paper


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.


Chronic cerebral hypoperfusion Cognition dysfunction Neuroinflammation Luteolin 



Amyloid β-protein 40


Activating protein-1


Blood–brain barrier


Bovine serum albumin


Chronic cerebral hypoperfusion


Complementary DNA


Control group






Enzyme-linked immunosorbent assay


Field excitatory postsynaptic potential


γ-Aminobutyric acid


Glyceraldehyde 3-phosphate dehydrogenase


Glial fibrillary acidic protein


Glutathione peroxidases


Horseradish peroxidase


High frequency stimulation


Ionized calcium-binding adapter molecule 1


Interleukin 1β


Interleukin 6






Kappa B-alpha


Inducible nitric oxide synthase


Kainic acid


Long-term potentiation


Luteolin treatment


Mouse monoclonal antibody


Mitogen-activated protein kinase




Morris water maze


National Natural Science Foundation of China


Nitric oxide


Perforant path


Novel object recognition test


Paired-pulse facilitation


Quantitative real time polymerase chain reaction


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Superoxide dismutase


Tumor necrosis factorα


Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling


Bilateral common carotid arteries ligation

2VO + Lut

2VO operation and luteolin treatment



This work was supported in part by Grants from the National Natural Science Foundation of China (NSFC) (81400891).

Compliance with Ethical Standards

Conflict of interest

All authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Zhao-Hui Yao
    • 1
  • Xiao-li Yao
    • 2
  • Yong Zhang
    • 3
  • Shao-feng Zhang
    • 3
  • Ji-chang Hu
    • 4
  1. 1.Department of GeriatricsRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of NeurologyCentral Hospital of ZhengzhouZhengzhouChina
  3. 3.Department of NeurologyRenmin Hospital of Wuhan UniversityWuhanChina
  4. 4.Department of PathologyRenmin Hospital of Wuhan UniversityWuhanChina

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