Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats.

Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats.
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木犀草素通过激活PPAR γ减轻大鼠脑缺血再灌注引起的海马炎症和自噬。

DOI:
10.1186/s12906-022-03652-8
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发表时间:
2022-07-01
影响因子:
3.9
通讯作者:
Qiu, Jiaoxue
Qiu, Jiaoxue
中科院分区:
医学3区
文献类型:
--
作者:
Li, Lu;Pan, Guanghua;Fan, Rong;Li, Dalei;Guo, Lei;Ma, Lili;Liang, Hui;Qiu, Jiaoxue

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木犀草素是一种具有抗炎活性的黄酮类化合物,已被报道可减轻脑缺血/再灌注(I/R)损伤。然而,其潜在机制仍不清楚。通过分子对接分析计算毛地黄黄酮与过氧化物酶体增殖物激活受体γ(PPARγ)的结合活性。采用大脑中动脉闭塞再灌注(MCAO/R)模型。再灌注后立即口服溶剂、25 mg/kg/d木犀草素、50 mg/kg/d木犀草素、10 mg/kg/d吡格列酮、50 mg/kg/d木犀草素联合10 mg/kg/d T0070907(PPARγ抑制剂)治疗7 d。采用酶联免疫吸附试验(ELISA)、TTC染色、H&E染色、免疫组化、免疫荧光和透射电镜等方法观察损伤海马区的炎症反应和自噬情况。检测损伤海马区过氧化物酶体增殖物激活受体γ(PPARγ)、轻链3(LC 3)B-Ⅱ/LC 3 B-Ⅰ和p-核因子-κB(NF-κB)p65蛋白的表达水平。根据对接评分(评分=-8.2),木犀草素显示出良好的PPARγ活性。木犀草素治疗下调MCAO/R损伤引起的梗死面积和促炎细胞因子水平。此外,毛地黄黄酮管理改善神经炎症和自噬损伤海马区。吡格列酮的保护作用与毛地黄黄酮相似。T0070907掩盖了50 mg/kg/d木犀草素的神经保护作用。木犀草素通过激活PPARγ对脑缺血再灌注大鼠海马炎症和自噬的保护作用在线版本包含补充材料,可通过10.1186/s12906-022-03652-8获得。
Luteolin, a flavonoid compound with anti-inflammatory activity, has been reported to alleviate cerebral ischemia/reperfusion (I/R) injury. However, its potential mechanism remains unclear. The binding activity of luteolin to peroxisome proliferator-activated receptor gamma (PPARγ) was calculated via molecular docking analysis. Rats were subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). After reperfusion, vehicle, 25 mg/kg/d luteolin, 50 mg/kg/d luteolin, 10 mg/kg/d pioglitazone, 50 mg/kg/d luteolin combined with 10 mg/kg/d T0070907 (PPARγ inhibitor) were immediately orally treatment for 7 days. ELISA, TTC staining, H&E staining, immunohistochemistry, immunofluorescence and transmission electron microscope methods were performed to evaluate the inflammation and autophagy in damaged hippocampal region. The PPARγ, light chain 3 (LC3) B-II/LC3B-I and p-nuclear factor-κB (NF-κB) p65 proteins expression levels in damaged hippocampal region were analyzed. Luteolin showed good PPARγ activity according to docking score (score = − 8.2). Luteolin treatment downregulated the infarct area and the pro-inflammatory cytokines levels caused by MCAO/R injury. Moreover, luteolin administration ameliorated neuroinflammation and autophagy in damaged hippocampal region. Pioglitazone plays protective roles similar to luteolin. T0070907 concealed the neuroprotective roles of 50 mg/kg/d luteolin. Luteolin exerts neuroprotective roles against inflammation and autophagy of hippocampus induced by cerebral I/R by activating PPARγ in rats. The online version contains supplementary material available at 10.1186/s12906-022-03652-8.
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