Xia Mao1, Haiyu Xu1, Sen Li2, Jin Su1, Weijie Li1, Qiuyan Guo1, Ping Wang1, Rui Guo3, Xuefeng Xiao4, Yanqiong Zhang5, Hongjun Yang6. 1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. 2. Department of Pharmaceutics, Hunan University of Chinese Medicine, Changsha 410208, China. 3. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. 4. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: kai1219@163.com. 5. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. Electronic address: yqzhang@icmm.ac.cn. 6. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. Electronic address: hjyang@icmm.ac.cn.
Abstract
BACKGROUND: Xueshuan-Xinmai-Ning Tablet (XXNT), a commercially available patent drug, has been extensively used in the treatment of coronary heart disease (CHD) with a satisfying therapeutic efficacy. The aim of this study was to explore the underlying pharmacological mechanisms of XXNT acting on CHD. STUDY DESIGN: An integrative pharmacology-based investigation was performed. METHOD: Putative targets of composite compounds contained in XXNT were predicted using the Drug Target Prediction Tool in the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine (TCMIP, www.tcmip.cn) and MedChem Studio. Then, an interaction network of XXNT putative targets-known CHD-related genes was constructed, and candidate XXNT targets related to its therapeutic effects on CHD were identified by calculating three major network topological features. Functional enrichment analysis was performed to investigate the specific functions and pathways involved by the candidate XXNT targets acting on CHD, which were further validated by in vitro experiments. RESULTS: A total of 742 putative targets hit 126 chemical components contained in XXNT were predicted. Following the construction of XXNT putative target-known CHD-related gene network, and the network topological feature calculation, we identified 51 candidate XXNT targets related to its therapeutic effects on CHD. Functionally, these candidate XXNT targets were significantly associated with various cardiovascular system-related pathways, sedation-related pathways, inflammatory and immune-related pathways and endocrine/metabolic system-related pathways. More importantly, the in vitro experiment validation confirmed the regulatory effects of XXNT in SRC, VEGF and VEGFR-1, which play roles in VEGF signaling pathway, based on the endothelial injury cell model. CONCLUSION: Our findings reveal that XXNT may attenuate the major pathological changes of CHD through regulating its candidate targets, which might be involved into the signal transductions in nervous-endocrine-immune-cardiovascular-metabolic system.
BACKGROUND: Xueshuan-Xinmai-Ning Tablet (XXNT), a commercially available patent drug, has been extensively used in the treatment of coronary heart disease (CHD) with a satisfying therapeutic efficacy. The aim of this study was to explore the underlying pharmacological mechanisms of XXNT acting on CHD. STUDY DESIGN: An integrative pharmacology-based investigation was performed. METHOD: Putative targets of composite compounds contained in XXNT were predicted using the Drug Target Prediction Tool in the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine (TCMIP, www.tcmip.cn) and MedChem Studio. Then, an interaction network of XXNT putative targets-known CHD-related genes was constructed, and candidate XXNT targets related to its therapeutic effects on CHD were identified by calculating three major network topological features. Functional enrichment analysis was performed to investigate the specific functions and pathways involved by the candidate XXNT targets acting on CHD, which were further validated by in vitro experiments. RESULTS: A total of 742 putative targets hit 126 chemical components contained in XXNT were predicted. Following the construction of XXNT putative target-known CHD-related gene network, and the network topological feature calculation, we identified 51 candidate XXNT targets related to its therapeutic effects on CHD. Functionally, these candidate XXNT targets were significantly associated with various cardiovascular system-related pathways, sedation-related pathways, inflammatory and immune-related pathways and endocrine/metabolic system-related pathways. More importantly, the in vitro experiment validation confirmed the regulatory effects of XXNT in SRC, VEGF and VEGFR-1, which play roles in VEGF signaling pathway, based on the endothelial injury cell model. CONCLUSION: Our findings reveal that XXNT may attenuate the major pathological changes of CHD through regulating its candidate targets, which might be involved into the signal transductions in nervous-endocrine-immune-cardiovascular-metabolic system.
Authors: Kun Xia Hu; Xi Duan; Li Zhu Han; Hong Ye Ju; Bin Wang; Zhi Shu Tang; Xiao Song Journal: Evid Based Complement Alternat Med Date: 2019-09-12 Impact factor: 2.629