title: Cardioprotective effects of tilianin in rat myocardial ischemia-reperfusion injury.
abstract: Tilianin, the main effective flavonoid monomer enriched from Dracocephalum moldavuca L., has been shown to have cardioprotective effects. However, the mechanism of tilianin cardioprotection remains largely unknown. The present study aimed to investigate the effects of tilianin preconditioning on myocardial ischemia/reperfusion injury and to analyze the possible mechanism of action. A total of 48 male Sprague Dawley rats were randomized into sham, model myocardial ischemia/reperfusion injury (MI/RI), propranolol hydrochloride positive control, and high‑, medium‑ and low‑dose tilianin groups (n=8 each). The rats in the tilianin groups were perfused with either 1.5, 2.5 or 5.0 mg/kg/d tilianin a week prior to surgery. The positive control group were perfused with 25 mg/kg/d propranolol. Saline was administered to the sham surgery and the MI/RI groups. The MI/RI model was established by ligating the left anterior descending coronary artery for 30 min, which was subsequently removed and the mice were observed for 120 min prior to sacrifice. Na+‑K+‑ATPase, Ca2+‑ATPase, nitric oxide (NO), nitric oxide synthase (NOS) and endothelial system‑related factors were analyzed using the respective detection kits. Immunohistochemistry was used to determine the expression levels of Bcl‑2 and Bax. Caspase‑3 activity was measured by quantitative polymerase chain reaction. The results showed that tilianin preconditioning significantly increased ATPase activity (P<0.01 and P<0.05) as compared with the model group. With regards to the regulation of endothelial function, significant decreases (P<0.01 and P<0.05) were detected in the serum NO levels and myocardial NOS activity when tilianin was administered to MI/RI rats, as compared with the model group, . In addition, the tilianin drug groups exhibited dose‑dependent reductions in the serum levels of endothelin 1 and thromboxane B2, and increases in the serum levels of calcitonin gene‑related peptide and 6‑keto prostaglandin F1a as compared with the model group (P<0.01 and P<0.05). Notably, the administration of tilianin significantly inhibited apoptosis, as evidenced by an increase in Bcl‑2 expression, and reductions in Bax and caspase‑3 mRNA expression levels (P<0.01 and P<0.05). These data indicate that pretreatment with tilianin exerts potent cardioprotective effects in rats with MI/RI. The anti‑MI/RI effects comprised relieving calcium overload, correction of energy metabolism, improvement of endothelial function and inhibiting cell apoptosis.
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Wenjiang
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Xinjiang Institute of Materia Medica, Ürümqi, Xinjiang 830004, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xing
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D005419:Flavonoids; D006027:Glycosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C426884:tilianin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D053148:Caspase 3; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase