木犀草素通过激活大鼠大脑中动脉缺血再灌注后海马区的过氧化物酶体增殖物激活受体γ减轻炎症和自噬。
Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats.
机构信息
Department of Electrophysiology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, 264200, China.
Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, 264200, China.
出版信息
BMC Complement Med Ther. 2022 Jul 1;22(1):176. doi: 10.1186/s12906-022-03652-8.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Luteolin exerts neuroprotective roles against inflammation and autophagy of hippocampus induced by cerebral I/R by activating PPARγ in rats.
背景
具有抗炎活性的类黄酮化合物木犀草素已被报道可减轻脑缺血/再灌注（I/R）损伤。然而，其潜在机制尚不清楚。
方法
通过分子对接分析计算木犀草素与过氧化物酶体增殖物激活受体γ（PPARγ）的结合活性。大鼠进行大脑中动脉闭塞再灌注（MCAO/R）。再灌注后，立即给予载体、25mg/kg/d 木犀草素、50mg/kg/d 木犀草素、10mg/kg/d 吡格列酮、50mg/kg/d 木犀草素联合 10mg/kg/d T0070907（PPARγ 抑制剂）进行 7 天口服治疗。采用 ELISA、TTC 染色、H&E 染色、免疫组化、免疫荧光和透射电镜方法评估损伤海马区的炎症和自噬。分析损伤海马区的 PPARγ、LC3B Ⅱ/LC3B-I 轻链和 p-核因子-κB（NF-κB）p65 蛋白表达水平。
结果
根据对接评分（评分为-8.2），木犀草素表现出良好的 PPARγ 活性。木犀草素治疗可下调 MCAO/R 损伤引起的梗死面积和促炎细胞因子水平。此外，木犀草素给药可改善损伤海马区的神经炎症和自噬。吡格列酮的作用与木犀草素相似。T0070907 掩盖了 50mg/kg/d 木犀草素的神经保护作用。
结论
木犀草素通过激活大鼠海马中的 PPARγ，发挥对脑 I/R 引起的炎症和自噬的神经保护作用。
Zotero 插件