Mechanistic insights into the amelioration effects of diabetic cardiomyopathy by berberine:an integrated systems pharmacology study and experimental validation  

作　　者：Hui-Min Ji Wen Yang Yu Hua Yi-Xuan Sun Ao-Di Li Yue Jiang Zi-Qi Ye Min Lei Xi-Ying Guo Xiu-Fen Liu Ning-Hua Wu Huan-Bo Cheng Qing-Jie Chen 

机构地区：[1]School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Xianning 437100,China [2]Hubei Key Laboratory of Diabetes and Angiopathy,Medicine Research Institute,Xianning Medical College,Hubei University of Science and Technology,Xianning 437100,China [3]School of Basic medical Sciences,Medicine Research Institute,Xianning Medical College,Hubei University of Science and Technology,Xianning 437100,China [4]Jin License Holding Zhengtang Pharmaceutical Co.,Ltd.,Huangshi 435100,China

出　　处：《Traditional Medicine Research》2025年第3期42-55,共14页TMR传统医学研究

基　　金：supported by the National Natural Science Foundation of China(Grant No.82270892);Natural Science Foundation of Hubei Province(Grant No.2022CFB287);Xianning City Science and Technology Plan Project(Grant No.2022ZRKX052);School projects of Hubei University of Science and Technology(Grant No.2022T01,2021WG05,2021TNB01);Hubei University of Science and Technology School-level Fund(Grant No.BK202122).

摘　　要：Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.

关 键 词：BERBERINE APOPTOSIS integrated systems pharmacology diabetic cardiomyopathy 

分 类 号：R542.2[医药卫生—心血管疾病]