Abstract
The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode.
Highlights
Cardiac hypertrophy (CH) is initially an adaptive response to pressure or volume stress, which is characterized by increased cardiomyocyte size, re-expression of fetal genes, and activation of signaling pathways governing protein synthesis[1]
Consistent with our previous study[12], the present study demonstrated the protective effect of QSYQ on pressure overload-induced cardiac hypertrophy (CH) in rats, as shown by improved heart function and macro and micromorphology
Similar to QSYQ, the active ingredients of QSYQ ASIV, DLA and R1 and their combinations exerted an antihypertrophic effect but with a less potency. These results proved the necessity of including all the ingredients in QSYQ, and provided further evidence supporting QSYQ as a potential option for protection of CH
Summary
Cardiac hypertrophy (CH) is initially an adaptive response to pressure or volume stress, which is characterized by increased cardiomyocyte size, re-expression of fetal genes, and activation of signaling pathways governing protein synthesis[1]. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β -blockers and Ca2+ channel blockers are the major agents for management of CH in clinic[7], while the mortality and morbidity of the syndrome remain unacceptably high[8]. This might be partly due to the fact that each of these agents acts on a single signaling pathway or target. By comparing the efficacies and mechanisms of QSYQ, its single ingredient ASIV, DLA, R1, DO and various ingredient combinations we showed the rationality of QSYQ formula design, supporting that a regime containing multiple components is more effective than individual treatment for complex diseases[16]
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