Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

Sun,Long; Xu,Peng; Fu,Tinggang; Huang,Xin; Song,Jie; Chen,Meng; Tian,Xinghan; Yin,Hongli; Han,Jichun

doi:10.3892/mmr.2017.8212

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

Authors:
- Long Sun
- Peng Xu
- Tinggang Fu
- Xin Huang
- Jie Song
- Meng Chen
- Xinghan Tian
- Hongli Yin
- Jichun Han
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Affiliations: Department of Neurosurgery, Lin Yi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Medicine, Yantai Yuhuangding Hospital of Laishan Branch, Yantai, Shandong 264003, P.R. China, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
Published online on: December 7, 2017 https://doi.org/10.3892/mmr.2017.8212
Pages: 3274-3280

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Abstract

The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low‑myricetin (1 mg/kg), medium‑myricetin (5 mg/kg) and high‑myricetin (25 mg/kg) groups. Neurological deficit scores were evaluated by an examiner blinded to the experimental groups. Brain infarct size was estimated macroscopically using 2,3,5‑triphenyltetrazolium chloride staining. The levels of inflammatory factors tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β, and oxidative stress index superoxide dismutase (SOD), malondiadehyde (MDA), and the glutathione/glutathione disulfide (GSH/GSSG) ratio were measured by ELISA. The degree of brain cell apoptosis was determined using a terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. Protein expression levels of total or phosphorylated p38 mitogen activated protein kinase (MAPK), nuclear factor (NF)‑κB/p65 and protein kinase B (AKT) were determined using a western blotting assay. The neurological deficit score and infarct area induced by pMCAO decreased in a dose‑dependent manner following myricetin treatment. Furthermore, myricetin reduced the expression levels of IL‑1β, IL‑6, TNF‑α, and MDA, and increased GSH/GSSG ratio and SOD activity. A significant decrease in cell apoptosis was observed in response to myricetin. In addition, myricetin significantly increased the level of phosphorylated AKT protein, and decreased the phosphorylation of p38 MAPK and the level of NF‑κB/p65. Overall, the results of the present study suggested that myricetin exhibits a therapeutic effect by reducing ischemic cerebral injury, and the protective effect of myricetin may be associated with the p38 MAPK, NF‑κB/p65 and AKT signaling pathways.

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