Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial

作者：Jun Liu, Dandan Li, Wei Dong, Yuqi Liu, Yang Wu, Da-Xuan Tang, Fuchun Zhang, Meng Qiu, Qi Hua, Jingyu He, Jun Li, Bai Du, Tinghai Du, Lin-Lin Niu, Xuejun Jiang, Bo Cui, Jiang-Bin Chen, Yang-Gan Wang, Hairong Wang, Hai-Rong Wang, Qin Yu, Jing He, Yilin Mao, Xiao-Fang Bin, Yue Deng, Yu-Dan Tian, Qing-Hua Han, Dajin Liu, Liqin Duan, Ming-Jun Zhao, Cui-Ying Zhang, Hai-Ying Dai, Ze-Hua Li, Ying Xiao, Xiaoyu Huang, Xiao-Yu Huang, Kun Xing, Xin Jiang, Chaofeng Liu, Jing An, Feng-Chun Li, Tao Tao, Jin-Fa Jiang, Ying Yang, Dong Yao-rong, Lei Zhang, Guang Fu, Ying Li, Shu-Wei Huang, Liping Dou, Lanjun Sun, Yingqiang Zhao, Jie Li, Yun Xia, Jun Liu, Fan Liu, Wen-Jin He, Ying Li, Jian-Cong Tan, Lin Yang, Yabin Zhou, Jian-Fei Yang, Guoqing Ma, Huijun Chen, He-Ping Liu, Jian-Xiong Liu, Jian-Xiong Liu, Xiao-Jia Luo, Xiao-Hong Bin, Yanan Yu, Haixia Dang, Bing Li, Fei Teng, Wangmin Qiao, Xiaolong Zhu, Qiguang Chen, Chunti Shen, Chun-Ti Shen, Yongyan Wang, Zhong Wang, Yundai Chen, Zhong Wang · 发表于：Signal Transduction and Targeted Therapy · 年份：2021 · DOI：10.1038/s41392-021-00741-x · 被引用次数：43 · 研究领域：Traditional Chinese Medicine Analysis、Metabolomics and Mass Spectrometry Studies、Pharmacological Effects of Natural Compounds

Abstract It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events ( P = 0.8502) and serious adverse events ( P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Z summary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as...