Systems-Pharmacology Dissection of Traditional Chinese Medicine Compound Saffron Formula Reveals Multi-scale Treatment Strategy for Cardiovascular Diseases

Cardiovascular diseases (CVDs) have been regarding as "the world's first killer" of human beings in recent years owing to the striking morbidity and mortality, the involved molecular mechanisms are extremely complex and remain unclear. Traditional Chinese medicine (TCM) adheres to the aim of combating complex diseases from an integrative and holistic point of view, which has shown effectiveness in CVDs therapy. However, system-level understanding of such a mechanism of multi-scale treatment strategy for CVDs is still difficult. Here, we developed a system pharmacology approach with the purpose of revealing the underlying molecular mechanisms exemplified by a famous compound saffron formula (CSF) in treating CVDs. First, by systems ADME analysis combined with drug targeting process, 103 potential active components and their corresponding 219 direct targets were retrieved and some key interactions were further experimentally validated. Based on this, the network relationships among active components, targets and diseases were further built to uncover the pharmacological actions of the drug. Finally, a "CVDs pathway" consisted of several regulatory modules was incorporated to dissect the therapeutic effects of CSF in different pathological features-relevant biological processes. All this demonstrates CSF has multi-scale curative activity in regulating CVD-related biological processes, which provides a new potential way for modern medicine in the treatment of complex diseases.