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Neuroprotective and Anti-inflammatory Effect of Tangeretin Against Cerebral Ischemia-Reperfusion Injury in Rats

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Abstract

The neuro-inflammation is well known to be an inflammatory response in the brain tissue. Anti-inflammatory therapy in ischemia/reperfusion (I/R) pathogenesis is a potential therapeutic strategy for post-I/R injury. Currently, we made attempt to scrutinize the neuro-protective effect of tangeretin against I/R injury in the brain of experimental rats. I/R injury is induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. mRNA expression of interleukin 6 (IL-6), toll-like receptor-4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFNG-γ), and transforming growth factor-β1 (TGF-β1) was estimated using the qRT-PCR. Tangeretin significantly (P < 0.001) decreased brain water content, infarct volume, neurological score, brain edema, and Evans blue leakage. Tangeretin significantly (P < 0.001) down-regulated the inflammatory and pro-inflammatory cytokines and oxidative stress parameters in the serum and brain tissue of experimental rats. qRT-PCR data demonstrated that rats treated with tangeretin could significantly (P < 0.001) suppress the IL-1β, TLR-4 TNF-α, IFNG-γ, and IL-6 and boost the expression of TGF-β1 compared with I/R injury rats. The result clearly showed tangeretin neuro-protective and anti-inflammatory effect against I/R injury in rats through suppressed inflammatory reaction.

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Abbreviations

I/R:

Ischemia/reperfusion

IL-6:

Interleukin 6

TLR-4:

Toll-like receptor-4

IL-1β:

Interleukin 1β

TNF-α:

Tumor necrosis factor α

IFNG-γ:

Interferon-γ

TGF-β1:

Transforming growth factor β1

iNOS:

Inducible nitric oxide synthase

PGE2 :

Prostaglandin E2

COX-2:

Cyclooxygenase-2

NF-κB:

Nuclear kappa B factor

MCAO:

Intraluminal middle cerebral artery occlusion

MCA:

Middle cerebral artery

EDTA:

Ethylenediaminetetraacetic acid

PBA:

Phosphate-buffered saline

GSH:

Glutathione

GPx:

Glutathione peroxidase

CAT:

Catalase

GR:

Glutathione reductase

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

ANOVA:

One-way variance analysis

ROS:

Reactive oxygen species

O2 :

Superoxide anion

H2O2 :

Hydrogen peroxide

NK:

Natural killer

NADPH:

Nicotinamide adenine dinucleotide phosphate

BBB:

Blood-brain barrier

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Funding

This study was supported by the National Natural Science Foundation of China (Nos. 81704170 and 81473763). This study was also supported by grants from the Heilongjiang Start-up Fund for Postdoctoral Research (No. LBH-Q18117) and Excellent leading talents support plan of the Heilongjiang University of Chinese Medicine (2018RCL11) and The Training Project of scientific research technology for young and middle-aged in Shenzhen People’s Hospital, 2ND Clinical Medical College of Jinan University (No. SYKYPY201925).

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Author notes

  1. Tiansong Yang, Chuwen Feng, Dongyan Wang, and Yuanyuan Qu contributed equally to this work and should be considered as Co-First authors.

Authors and Affiliations

  1. First Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 26 Heping Road, Xiangfang District, Harbin, 150036, China

    Tiansong Yang & Chuwen Feng

  2. Heilongjiang University of Chinese Medicine, No. 24 HepingRoad, Xiangfang District, Harbin, 150036, China

    Tiansong Yang, Chuwen Feng, Dongyan Wang, Yuanyuan Qu, Yan Yang & Zhongren Sun

  3. Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 411 Guogeli Street, Nangang District, Harbin, 150000, China

    Yulin Wang

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  1. Tiansong Yang
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  5. Yan Yang
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Yang, T., Feng, C., Wang, D. et al. Neuroprotective and Anti-inflammatory Effect of Tangeretin Against Cerebral Ischemia-Reperfusion Injury in Rats. Inflammation 43, 2332–2343 (2020). https://doi.org/10.1007/s10753-020-01303-z

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