Abstract
Abstract
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.
Funder
the National Natural Science Foundation of the People’s Republic of China
The Key Technology Projects of China “Creation of New Drugs”
the Social Development Project for Jiangsu Province
the Project of National Traditional Chinese Medicine Standardization
Tianjin Science & Technology Plan Project
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Biochemistry,Endocrinology, Diabetes and Metabolism
Cited by
18 articles.
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