Berberine could ameliorate cardiac dysfunction via regulating myocardial lipidmics profiling in the rat model of diabetic cardiomyopathy

[Speaker] Shifen Dong:1
[Co-author] Long Cheng:1, Linyue Tian:1, Rong Zhang:1, Yaoyue Liang:1, Fei Shang:2, Jianning Sun:1
1:School of Chinese Materia Medica, Beijing University of Chinese Medicine, China, 2:Beijing University of Chemical Technology, Beijing, China

Background: Diabetic cardiomyopathy (DCM) could lead to changes in the structure and contractility of the myocardium, which are initiated in part by alterations in energy substrates. The aim of this research was to detect the effect of berberine on changes of myocardial lipidomics profiling in diabetic cardiomyopathy rats using UPLC/Q-TOF/MS analysis, and identify potential biomarkers for further research and therapy in the future.
Methods: DCM was induced by feeding a high-sucrose/fat diet (HSFD) for 22 weeks and streptozotocin (30 mg/kg, intraperitoneally). DCM rats were given with berberine at a dosage of 10 and 30 mg/kg 72 h after streptozotocin injection at the 5th week of high diet feeding for consecutive 16 weeks. The UPLC/Q-TOF/MS spectrometer was used for acquiring and analyzing the lipidomics profiling of myocardial tissue. Meanwhile, parameters of cardiac function were collected using cardiac catheterization, and the cardiac index was calculated, and fasting blood glucose and lipid levels were measured by an ultraviolet spectrophotometric method.
Results: Diastolic dysfunction occurred four to five weeks after i.p. injection with STZ and high fat/high sucrose diet. Cardiac diastolic and systolic function could be attenuated with berberine treatment. Berberine caused a significant decrease in LVEDP from week 9 to 22 in DCM model rats. Meanwhile, berberine could ameliorate cardiac systolic function including LVSP and dp/dtmin significantly. We detected 2213 positive ion peaks and 301 negative ion peaks. Levels of phosphatidylethanolamine (PE), PE(P-16:0/20:4), PE(18:1/18:3), phosphatidylcholine (PC) (18:2/16:0), PE(20:4/18:2), PC(22:4/14:0), PC(18:4/20:1), PC(20:4/18:0), PC(20:4/20:4) and PC(22:4/18:1) were down-regulated, and PC(18:2/18:0) and PC(20:3/20:4) were up-regulated in DCM model rats, when compared with control rats. PE (18:2/16:0) could be increased with berberine 30 mg/kg treatment, meanwhile, metabolites including PE (18:2/16:0), PE (18:1/18:3) and PE(20:4/18:2) could be increased by berberine 10 mg/kg treatment.
Conclusions: UPLC-Q-TOF/MS analysis data suggested changes of some potential lipid biomarkers that could be reversed in the development of cardiac dysfunction and hypertrophy of diabetic cardiomyopathy, which may serve as potential important targets for clinical diagnosis and therapeutic intervention of DCM in the future.
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