Mechanistic insights into the amelioration effects of diabetic cardiomyopathy by berberine: An integrated systems pharmacology study and experimental validation
Description
Background: Diabetic cardiomyopathyis a type of cardiomyopathy caused by long-term diabetes mellitus that differs from hypertension and coronary heart disease. It is distinguished by abnormal myocardial structure and function, which can result in heart failure. Berberine, a monomer compound derived from the ancient Chinese medicine Coptis chinensis Franch, was discovered to have excellent anti-diabetes and heart-protective properties. The purpose of this study is to determine the effect of berberine on diabetes cardiomyopathy. Methods: The related proteins and signaling pathways between berberine and the target molecular of diabetes cardiomyopathy were evaluated using the systems pharmacology method. Experimental validation followed using diabetic mouse heart sections. Microstructural and pathological alterations were visible after HE, Masson, and WGA staining. With the help of immunofluorescence and Western blot, protein expression was identified. Results: 21 core relevant targets between diabetic cardiomyopathy and berberine were identified through systematic pharmacological studies. And the cross-targets were mostly found in mitochondrial, endoplasmic reticulum, and plasma membrane components. The PI3K/Akt and apoptosis signaling pathways were the most important. Moreover, the changes in berberine's core targets caspase-3, PI3K/Akt, and mitochondria-related proteins after treatment indicated that it had some effect. Conclusion: The results show that the use of berberine improves the morphological changes of the heart caused by diabetes and maintains the homeostasis of mitochondria and inhibits apoptosis, but we do not know the link between them and more experimental data are needed to explore the mechanism