title: Calycosin‑7‑O‑β‑D‑glucoside attenuates ischemia‑reperfusion injury in vivo via activation of the PI3K/Akt pathway.
abstract: The aim of the present study was to investigate the effects and mechanisms of calycosin‑7‑O‑β‑D‑glucoside (CG) on ischemia‑reperfusion (I/R) injury in vivo. Hemodynamic parameters, including ejection fraction (EF), fractional shortening (FS), left ventricular end‑systolic pressure (LVESP) and left ventricular end‑diastolic pressure (LVEDP) were monitored using an ultrasound system, and infarct size was measured using Evans blue/tetrazolium chloride double staining. The activities of serum creatine kinase (CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) were determined to assess the degree of myocardial injury and oxidative stress‑induced damage. The protein expression levels of cleaved‑caspase‑3, cleaved‑caspase‑9, phosphorylated (p)‑phosphatidylinositol 3‑kinase (PI3K) p85, PI3K p85, p‑Akt and Akt were determined using western blotting. The results demonstrated that pretreatment with high dose (H)‑CG markedly improved cardiac function, as evidenced by upregulated EF, FS and LVESP, and downregulated LVEDP. In addition, administration of CG resulted in significant decreases in infarct size in the I/R+low dose‑CG and I/R+H‑CG groups, compared with the I/R group. The activities of CK and LDH, and the levels of MDA in the I/R+H‑CG group were reduced, compared with those in the I/R group, whereas SOD activity was elevated. Treatment with CG inhibited the cleavage and activity of caspase‑3 and caspase‑9, and enhanced the phosphorylation of PI3K p85 and Akt. Notably, administration of the PI3K inhibitor, LY294002, markedly lowered the levels of p‑PI3K p85/p‑Akt, and eradicated the inhibitory effects of H‑CG on infarct size, myocardial injury and oxidative stress‑induced damage. Taken together, the results suggested that CG may alleviate I/R injury by activating the PI3K/Akt signaling pathway.
authors.affiliation: Department of Medical Ultrasonics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Medical Ultrasonics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Ultrasonics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Du
authors.affiliation: Department of Medical Ultrasonics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Medical Ultrasonics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002867:Chromones; D005960:Glucosides; D007529:Isoflavones; D009025:Morpholines; C526426:calycosin-7-O-beta-D-glucoside; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007770:L-Lactate Dehydrogenase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase