Abstract
Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.
Highlights
The cardiovascular diseases (CVDs) are major causes of death universally
Regarding the underlying mechanisms and interrelated biological elements of the SND, there are plentiful problems need to be solved imminently: 1) which positive elements take part in the administrative processes of the SND in the treatment of CVDs? 2) Which targets are regulated by the active chemical components to achieve the therapeutic goal? 3) Which pathologic processes are adjusted by the active ingredients and drugs to cure CVDs?
We applied system pharmacology methods to reveal the therapeutic effects of SND (Fig. 1), which comprise: 1) molecular database construction for the 3 drugs in SND; 2) ADME system evaluation to filter potential active components from the above compound database; 3) target-fishing of the obtained potential active components; 4) network construction and analysis to illustrate the underlying molecular mechanisms of SND in curing CVDs
Summary
The cardiovascular diseases (CVDs) are major causes of death universally. In 2012, about 17.5 million peoples died from CVDs representing about 31% of all deaths around the world and the death rates would be estimated to increase 23.6 million by 2030. There are many different drugs have been used to treat CVDs, mainly including antianginal drugs, anti-arrhythmic drugs, anti-coagulant medicine, blood-lipid lowering drugs, anti-hypertensive agents, beta-blockers, calcium blockers, cardiac glycosides, hydragog and vasodilator agents (Khand et al 2000, Shu et al 2018). These drugs are mostly playing vital roles in the single-compound and single-target, which bring many serious side effects, such as postural hyperpiesia, depressed and feeble from beta-blockers, sychnosphygmia, headache, facial flushing and polyuria from calcium blockers (Russell 1988, Yatoo et al 2017). The system pharmacology method would provide a novel and efficient way to deeply dissect the chemical and pharmacological basis of SND, which would promote the development of TCMs in the treatment of complex diseases
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