17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone Ameliorates Myocardial Ischemia/Reperfusion Injury in Rat by Inhibiting Apoptosis and Autophagy Via the PI3K–Akt Signal Pathway

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• 作者：Feifei Xuan ; Jie Jian ; Xing Lin ; Jianchun Huang ; Yang Jiao…
• 关键词：MHBFC ; Ischemia/reperfusion ; Apoptosis ; Autophagy ; PI3K–Akt
• 刊名：Cardiovascular Toxicology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：17
• 期：1
• 页码：79-87
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Cardiology;
• 出版者：Springer US
• ISSN：1559-0259
• 卷排序：17

文摘

17-Methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC), a monomer isolated from the root of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei (Papilionaceae), has been demonstrated to exhibit protective effects on myocardial ischemia/reperfusion (I/R) injury in rats. However, the mechanisms for the effect are not completely clear. In the present study, we tested whether MHBFC could reduce I/R-induced apoptosis and overautophagy via the PI3K–Akt pathway. The rat I/R model was established by ligating the left anterior descending coronary artery for 30 min and then followed by reperfusion for 2 h. MHBFC (10 mg/kg, intravenously) was administered alone or along with LY294002 (PI3K inhibitor, 0.3 mg/kg, intravenously) 5 min before the onset of reperfusion. We found that MHBFC postconditioning prevented I/R-induced release of creatine kinase-MB and tumor necrosis factor-α, inhibited the opening of mitochondrial permeability transition pore, and promoted nitric oxide production. Additionally, MHBFC caused a significant increase in PI3K, phosphorylation of Akt, mammalian target of rapamycin, and endothelial nitric oxide synthase, and a decrease in the expression of cleaved caspase-3, Beclin1, and conversion of microtubule-associated protein 1 light chain 3. However, the above functions of MHBFC were blocked by LY294002. These observations indicate that MHBFC plays a protective role against myocardial I/R injury by inhibiting apoptosis and excessive autophagy, which might be related to the activation of the PI3K–Akt signal pathway.