YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation

Frontiers in Endocrinology

Endocrinology

Furong Wang¹  Lina Wang¹  Yu Tang¹  Baolei Dou¹  Yingying Zhu¹  Shuo Tian¹  Wei Wang¹  Ruixia Liu² 

[1] College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China;Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China;

关键词: diabetic cardiomyopathy;    molecular docking;    network pharmacology;    Nrf2;    NQO1;    SIRT1;    YuNü-Jian;   

DOI  :  10.3389/fendo.2023.1195149

 received in 2023-03-28, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionDiabetic cardiomyopathy (DCM) is one of the most prevalent complications of diabetes with complex pathogenesis. YuNü-Jian (YNJ) is a traditional Chinese medicinal formula widely used for diabetes with hypoglycemic and cardioprotective effects. This study aims to investigate the actions and mechanisms of YNJ against DCM which has never been reported.MethodsNetwork pharmacology approach was used to predict the potential pathways and targets of YNJ on DCM. Molecular docking between hub targets and active components of YNJ was performed and visualized by AutoDock Vina and PyMOL. Then type 2 diabetic model was employed and intervened with YNJ for 10 weeks to further validate these critical targets.ResultsFirst, a total of 32 main ingredients of YNJ were identified and 700 potential targets were screened to construct herb-compound-target network. Then 94 differentially expressed genes of DCM were identified from GEO database. After that, PPI network of DCM and YNJ were generated from which hub genes (SIRT1, Nrf2, NQO1, MYC and APP) were assessed by topology analysis. Next, functional and pathway analysis indicated that the candidate targets were enriched in response to oxidative stress and Nrf2 signaling pathway. Furthermore, molecular docking revealed strong affinity between core targets and active components of YNJ. Finally, in rats with type 2 diabetes, YNJ obviously attenuated cardiac collagen accumulation and degree of fibrosis. Meanwhile, YNJ significantly upregulated protein expression of SIRT1, Nrf2 and NQO1 in diabetic myocardium.DiscussionCollectively, our findings suggested that YNJ could effectively ameliorate cardiomyopathy induced by diabetes possibly through SIRT1/Nrf2/NQO1 signaling.

【 授权许可】

Unknown   
Copyright © 2023 Wang, Liu, Zhu, Wang, Tang, Dou, Tian and Wang