Lin Li1,2, Dongli Yang1,2, Jinghao Li1,2, Lu Niu1,2, Ye Chen1,2, Xin Zhao1,2, Patrick Kwabena Oduro1,2, Chun Wei3, Zongpei Xu2, Qilong Wang4,5, Yuhong Li6,7. 1. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. 2. Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. 3. Tianjin Medical University Cancer Hospital, Tianjin, 300060, China. 4. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. wangqilong_00@tjutcm.edu.cn. 5. Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. wangqilong_00@tjutcm.edu.cn. 6. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. liyuhong@tjutcm.edu.cn. 7. Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. liyuhong@tjutcm.edu.cn.
Abstract
BACKGROUND: Shenmai injection (SMI) has been used in the treatment of cardiovascular disease (CVD), such as heart failure, myocardial ischemia and coronary heart disease. It has been found to have efficacy on doxorubicin (DOX)-induced cardiomyopathy. The aims of this study were to explore the underlying molecular mechanisms of SMI treatment on CVD by using network pharmacology and its protective effect on DOX-induced cardiotoxicity by in vitro and in vivo experiment based on network pharmacology prediction. METHODS: Network pharmacology method was used to reveal the relationship between ingredient-target-disease and function-pathway of SMI on the treatment of CVD. Chemical ingredients of SMI were collected form TCMSP, BATMAN-TCM and HIT Database. Drugbank, DisGeNET and OMIM Database were used to obtain potential targets for CVD. Networks were visualized utilizing Cytoscape software, and the enrichment analysis was performed using IPA system. Finally, cardioprotective effects and predictive mechanism confirmation of SMI were investigated in H9c2 rat cardiomyocytes and DOX-injured C57BL/6 mice. RESULTS: An ingredient-target-disease & function-pathway network demonstrated that 28 ingredients derived from SMI modulated 132 common targets shared by SMI and CVD. The analysis of diseases & functions, top pathways and upstream regulators indicated that the cardioprotective effects of SMI might be associated with 28 potential ingredients, which regulated the 132 targets in cardiovascular disease through regulation of G protein-coupled receptor signaling. In DOX-injured H9c2 cardiomyocytes, SMI increased cardiomyocytes viability, prevented cell apoptosis and increased PI3K and p-Akt expression. This protective effect was markedly weakened by PI3K inhibitor LY294002. In DOX-treated mice, SMI treatment improved cardiac function, including enhancement of ejection fraction and fractional shortening. CONCLUSIONS: Collectively, the protective effects of SMI on DOX-induced cardiotoxicity are possibly related to the activation of the PI3K/Akt pathway, as the downstream of G protein-coupled receptor signaling pathway.
BACKGROUND: Shenmai injection (SMI) has been used in the treatment of cardiovascular disease (CVD), such as heart failure, myocardial ischemia and coronary heart disease. It has been found to have efficacy on doxorubicin (DOX)-induced cardiomyopathy. The aims of this study were to explore the underlying molecular mechanisms of SMI treatment on CVD by using network pharmacology and its protective effect on DOX-induced cardiotoxicity by in vitro and in vivo experiment based on network pharmacology prediction. METHODS: Network pharmacology method was used to reveal the relationship between ingredient-target-disease and function-pathway of SMI on the treatment of CVD. Chemical ingredients of SMI were collected form TCMSP, BATMAN-TCM and HIT Database. Drugbank, DisGeNET and OMIM Database were used to obtain potential targets for CVD. Networks were visualized utilizing Cytoscape software, and the enrichment analysis was performed using IPA system. Finally, cardioprotective effects and predictive mechanism confirmation of SMI were investigated in H9c2rat cardiomyocytes and DOX-injured C57BL/6 mice. RESULTS: An ingredient-target-disease & function-pathway network demonstrated that 28 ingredients derived from SMI modulated 132 common targets shared by SMI and CVD. The analysis of diseases & functions, top pathways and upstream regulators indicated that the cardioprotective effects of SMI might be associated with 28 potential ingredients, which regulated the 132 targets in cardiovascular disease through regulation of G protein-coupled receptor signaling. In DOX-injured H9c2 cardiomyocytes, SMI increased cardiomyocytes viability, prevented cell apoptosis and increased PI3K and p-Akt expression. This protective effect was markedly weakened by PI3K inhibitor LY294002. In DOX-treated mice, SMI treatment improved cardiac function, including enhancement of ejection fraction and fractional shortening. CONCLUSIONS: Collectively, the protective effects of SMI on DOX-induced cardiotoxicity are possibly related to the activation of the PI3K/Akt pathway, as the downstream of G protein-coupled receptor signaling pathway.
Authors: Min Zhao; Qiufang Chen; Hong Wang; Wanfeng Xu; Jiayong Yang; Lijuan Cao Journal: Evid Based Complement Alternat Med Date: 2022-03-18 Impact factor: 2.629