Cardioprotective effects of hydroxysafflor yellow A on diabetic cardiac insufficiency attributed to up-regulation of the expression of intracellular calcium handling proteins of sarcoplasmic reticulum in rats.
Depressed sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) and Ca(2+)-release channels (ryanodine receptor RyR2) are involved in diabetic cardiomyopathy, however, the implication of intracellular calcium handling proteins in SR is undefined. It was hypothesized that the down-regulation of the intracellular calcium handling proteins of SR is closely related to an up-regulated endothelin (ET) system. Hydroxysafflor yellow A (HSYA) is expected to ameliorate cardiac insufficiency which is mediated by the depressed intracellular calcium handling system in diabetic rat heart. Diabetes was produced in male rats 8 weeks after an injection of streptozotocin (60 mg/kg i.p.) and HSYA was administered (100 mg/kg) by gavage in the last 4 weeks. Hemodynamic and echocardiographic changes, cardiac calcium handling proteins, serum biochemistry, ET system and redox were measured. The compromised cardiac function in diabetic rats was accompanied by a significant down-regulation of the expression of RyR2, FKBP12.6 as well as SERCA2a and PLB. These were closely linked with oxidative stress, an increased ET-1 and up-regulation of ECE, PropreET-1 and iNOS mRNA in diabetic cardiomyopathy. After a 4 week treatment with HSYA, all abnormalities were reversed significantly. In conclusion, diabetic cardiomyopathy was correlated with an abnormal expression of calcium handing proteins in SR and an activated ET-ROS (reactive oxygen species) system in the diabetic affected myocardium. HSYA significantly improved the cardiac function and down-regulated the ET system and ROS pathway, resulting in a reversal of the abnormalities of expression of calcium handing proteins and the cardiac performance in diabetic cardiomyopathy.
He
Haibo
H
Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Liu
Qiuju
Q
Shi
Mengqiong
M
Zeng
Xiaowei
X
Yang
Jun
J
Wu
Limao
L
Li
Lianda
L
D000284:Administration, Oral; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D004562:Electrocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010860:Pigments, Biological / Q000627:therapeutic use*; D011809:Quinones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D010860:Pigments, Biological; D011809:Quinones; D017382:Reactive Oxygen Species; C085278:hydroxysafflor yellow A; D002599:Chalcone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases