Compound danshen dripping pills normalize a reprogrammed metabolism of myocardial ischemia rats to interpret its time-dependent efficacy in clinic trials: a metabolomic study.

Autor: Aa N; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Avenue, Nanjing, 210029, China., Guo JH; Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.; Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Pujihe East Road, Tianjin, 300410, China., Cao B; Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.; Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210009, China., Sun RB; Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China., Ma XH; Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Pujihe East Road, Tianjin, 300410, China., Chu Y; Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Pujihe East Road, Tianjin, 300410, China., Zhou SP; Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Pujihe East Road, Tianjin, 300410, China., Aa JY; Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China., Yang ZJ; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Avenue, Nanjing, 210029, China. zhijianyangnj@njmu.edu.cn., Sun H; Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Pujihe East Road, Tianjin, 300410, China., Wang GJ; Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China. guangjiwang@hotmail.com.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2019 Sep 20; Vol. 15 (10), pp. 128. Date of Electronic Publication: 2019 Sep 20.
DOI: 10.1007/s11306-019-1577-3
Abstrakt: Introduction: Clinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment.
Objectives: This article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials.
Methods: A rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model.
Results: CDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively.
Conclusion: Metabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases.
Databáze: MEDLINE
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