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

Abstract

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 Neuroinflammation Luteolin 

Abbreviations

40

Amyloid β-protein 40

AP-1

Activating protein-1

BBB

Blood–brain barrier

BSA

Bovine serum albumin

CCH

Chronic cerebral hypoperfusion

cDNA

Complementary DNA

Con

Control group

COX-2

Cyclooxygenase-2

DAB

Diaminobenzidine

ELISA

Enzyme-linked immunosorbent assay

fEPSPs

Field excitatory postsynaptic potential

GABA

γ-Aminobutyric acid

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

GFAP

Glial fibrillary acidic protein

GPx

Glutathione peroxidases

HRP

Horseradish peroxidase

HFS

High frequency stimulation

IBA-1

Ionized calcium-binding adapter molecule 1

IL-1β

Interleukin 1β

IL-6

Interleukin 6

IL-8

Interleukin-8

LPS

Lipopolysaccharide

IκB-α

Kappa B-alpha

iNOS

Inducible nitric oxide synthase

KA

Kainic acid

LTP

Long-term potentiation

Lut

Luteolin treatment

mAb

Mouse monoclonal antibody

MAPK

Mitogen-activated protein kinase

MDA

Malondialdehyde

MWM

Morris water maze

NSFC

National Natural Science Foundation of China

NO

Nitric oxide

PP

Perforant path

NOR

Novel object recognition test

PPF

Paired-pulse facilitation

qRT-PCR

Quantitative real time polymerase chain reaction

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SOD

Superoxide dismutase

TNF-α

Tumor necrosis factorα

TUNEL

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

2VO

Bilateral common carotid arteries ligation

2VO + Lut

2VO operation and luteolin treatment

Notes

Acknowledgements

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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