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.
Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Haibo
H
He
Qiuju
Q
Liu
Mengqiong
M
Shi
Xiaowei
X
Zeng
Jun
J
Yang
Limao
L
Wu
Lianda
L
Li
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