title: 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone Ameliorates Myocardial Ischemia/Reperfusion Injury in Rat by Inhibiting Apoptosis and Autophagy Via the PI3K-Akt Signal Pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Xuan
authors.affiliation: Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin, 541004, Guangxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jian
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Wansu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Juman
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning, 530021, Guangxi, China. huangrenbin518@163.com.
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D047188:Chalcones / Q000008:administration & dosage / Q000494:pharmacology*; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C578356:17-methoxyl-7-hydroxy-benzene-furanchalcone; D051017:Apoptosis Regulatory Proteins; D047188:Chalcones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C546845:mTOR protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D052279:Creatine Kinase, MB Form
keywords: Apoptosis; Autophagy; Ischemia/reperfusion; MHBFC; PI3K–Akt