Neuroprotective and Anti-inflammatory Effect of Tangeretin Against Cerebral Ischemia-Reperfusion Injury in Rats
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ORIGINAL ARTICLE
Neuroprotective and Anti-inflammatory Effect of Tangeretin Against Cerebral Ischemia-Reperfusion Injury in Rats Tiansong Yang,1,2 Chuwen Feng,1,2 Dongyan Wang,2 Yuanyuan Qu,2 Yan Yang,2 Yulin Wang,3 and Zhongren Sun 2,4
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 neuroprotective 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 (IL1β), 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
Tiansong Yang, Chuwen Feng, Dongyan Wang, and Yuanyuan Qu contributed equally to this work and should be considered as Co-First authors. 1
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 26 Heping Road, Xiangfang District, Harbin, 150036, China 2 Heilongjiang University of Chinese Medicine, No. 24 HepingRoad, Xiangfang District, Harbin, 150036, China 3 Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 411 Guogeli Street, Nangang District, Harbin, 150000, China 4 To whom correspondence should be addressed at Heilongjiang University of Chinese Medicine, No. 24 HepingRoad, Xiangfang District, Harbin, 150036, China. E-mail: [email protected]
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; qRTPCR, Quantitative reverse transcription polymerase chain reaction; ANOVA, One-way variance analysis; ROS, Reactive oxygen species; O2, Superoxide anion;
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