Protective Effects And Mechanism Of Cinnamon And Its Main Effective Components On Diabetic Cardiopathy

Background:Diabetes has become the third largest noncommunicable disease in the world after cardiovascular diseases and cancers.Diabetic complications are the principal cause of increased diabetic mortality.Among them,diabetic cardiopathy is one of the most serious complications of diabetes,which seriously affects cardiac function and even causes sudden death.At present,there is a lack of effective preventive and therapeutic drugs for diabetic cardiopathy.Cinnamon is the dried bark of Cinnamomum cassia Presl.Its main components are cinnamaldehyde and cinnamon polyphenols.They have been studied on cardiovascular protection,but no studies have been reported about the protective effect on diabetic cardiopathy.Objective:This study was to investigate the cardioprotective effect of cinnamon and its main components on rats with diabetic cardiopathy and then study the mechanisms of their heart protection.Methods:1.Protective effect of cinnamon on diabetic cardiopathy:SD rats were randomly divided into the normal control and model groups.The diabetes model in rats was established by single intraperitoneal injection of 1%streptozotocin（STZ）at a dose of 85 mg/kg.Rats with fasting blood glucose（FBG）level≥16.7 mmol/L were regarded as successful models.The rats with successfully modelled were randomly divided into the STZ control,captopril（50 mg/kg）and cinnamon（0.75 g/kg）groups,each group of 8.Rats in the normal and STZ control groups were given distilled water of equal volume,while rats in the other groups were given intragastric administration according to the set doses.After 26 days,rats were anesthetized and then electrocardiogram（ECG）was measured.After collecting blood,the rats were executed.Left ventricular weight index（LVWI,ratio of left ventricular weight to body weight）was calculated after separating the heart and weighing the left ventricle.Serum levels of FBG,triglyceride（TG）,total cholesterol（TC）,high-density lipoprotein（HDL-C）,low-density lipoprotein（LDL-C）and brain natriuretic peptide（BNP）were measured after separating serum and myocardial ATPase activities and contents of energy products were measured,including phosphocreatine（PCr）,adenosine triphosphate（ATP）,asenosine diphosphate（ADP）,asenosine monophosphate（AMP）.2.Protective effect and mechanism of main effective components of cinnamon on diabetic cardiopathy:SD rats were randomly divided into the normal and model groups.The diabetes model in rats was established by single intraperitoneal injection of 1%STZ at a dose of 85 mg/kg.Rats with FBG level≥16.7 mmol/L were regarded as successful models.The rats with successfully modelled were randomly divided into the STZ control,low dose of cinnamon（0.75g/kg）,high dose of cinnamon（1.5 g/kg）,cinnamaldehyde（CA）（47.5 mg/kg）and cinnamon polyphenols（CP）（135 mg/kg）groups,each group of 8.Rats in the normal and STZ control groups were given distilled water of equal volume,while rats in the other groups were given intragastric administration according to the set doses.After26 days,rats were anesthetized and then ECG was measured.After collecting blood,the rats were executed.LVWI was calculated after separating the heart and weighing the left ventricle.Serum levels of FBG,TG,TC,HDL-C,LDL-C and BNP after separating serum were measured.Myocardial total superoxide dismutase（T-SOD）activity,malondialdehyde（MDA）content and ATPase activities were tested.Contents of energy products in myocardial tissue and gene expressions of AMP-activated protein kinase（AMPK）related signaling pathway were detected.Results:1.Protective effect of cinnamon on diabetic cardiopathy:The LVWI and serum levels of FBG,TG,TC,HDL-C,LDL-C and BNP in the STZ control group were significantly increased.The segment of S-T of ECG was elevated,and the intervals of P-R,Q-T and QRS of ECG were prolonged.In addition,the heart rate was slowed,and the body weight,the activities of Ca²⁺Mg²⁺-ATPase and Na⁺K⁺-ATPase in myocardial tissue and the contents of PCr,ATP,ADP and AMP were significantly decreased.The serum levels of TG,TC,LDL-C and BNP were significantly decreased,the intervals of QRS and P-R of ECG were significantly shortened,the Ca²⁺Mg²⁺-ATPase activity and the contents of PCr,ATP and ADP in myocardial tissue were increased significantly by cinnamon.2.Protective effect and mechanism of main effective components of cinnamon on diabetic cardiopathy:The LVWI,serum levels of FBG,TG,TC,HDL-C,LDL-C and BNP,myocardial MDA content in the STZ control group were significantly increased.The segment of S-T of ECG was elevated,and the intervals of P-R and Q-T of ECG were prolonged.In addition,the heart rate was slowed.And the body weight（BW）,the activities of Ca²⁺Mg²⁺-ATPase and Na⁺K⁺-ATPase,the contents of PCr and AMP and PCr/ATP in myocardial tissue were significantly decreased.The expressions of AMP-activated protein kinase catalytic subunit alpha-2（AMPK-α₂）,peroxisome proliferator-activated receptor alpha（PPAR-α）and peroxisome proliferator-activated receptorγcoactivator 1-alpha（PGC-1α）in myocardium of STZ-induced rats were increased.The doses of 0.75 and1.50 g/kg cinnamon effectively shortened P-R interval of ECG,reversed the slowed heart rate,reduced serum LDL-C level and myocardial MDA content,and increased AMP content and PCr/ATP level in myocardial issue.The dose of 0.75 g/kg cinnamon increased Ca²⁺Mg²⁺-ATPase activity in myocardial tissue.The dosage of1.50 g/kg cinnamon significantly reduced BNP level and ATP content.CA and CP effectively depressed S-T segment and shortened P-R interval of ECG,resisted the increase of LDL-C and BNP levels,MDA and ATP contents,and enhanced the activity of Ca²⁺Mg²⁺-ATPase and PCr/ATP.CA significantly reduced serum FBG level.CP significantly reversed the slowed heart rate,increased AMP content in myocardial tissue,and reduced ADP content.The expressions of AMPK-α₂and PPAR-αin myocardium of rats in the dose of 0.75 g/kg cinnamon group were significantly decreased,the expressions of AMPK-α₂,PPAR-αand PGC-1αin CA group were significantly decreased,and the expression of AMPK-α₂in CP group was significantly decreased.Conclusion:Cinnamon has protective effect on diabetic cardiopathy.It may improve the myocardial injury in diabetic rats by regulating myocardial energy metabolism.CA and CP can improve myocardial energy metabolism disorder by enhancing ATPase activities and downregulating AMPK-α₂pathway.The regulation of energy metabolism by AMPK-α₂/PGC-1α/PPAR-αsignaling pathway may be one of the mechanisms of CA against diabetic cardiopathy.