• Feifei Xuan, Jie Jian, Xing Lin, Jianchun Huang, Yang Jiao, Wansu Huang, Juman Li, Zhi Shi, and Renbin Huang.
• Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
• Cardiovasc. Toxicol. 2017 Jan 1; 17 (1): 79-87.

Abstract17-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.

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