A Systems Biology Perspective on the Molecular Mechanisms Underlying the Therapeutic Effects of Buyang Huanwu Decoction on Ischemic Stroke.

Ischemic stroke is the leading cause of adult disability worldwide. The outcome is worse in older patients, especially in terms of disability. Buyang Huanwu decoction (BHD), a famous traditional Chinese medicine formula, has been used extensively in the treatment of ischemic stroke for centuries. However, its pharmacological mechanisms have not been fully elucidated. In this study, 82 putative targets for 411 composite compounds contained in BHD were predicted on the basis of our previously developed target prediction system. On the basis of large-scale molecular docking, more than 80% compound-putative target pairs had medium to strong binding efficiency. The pharmacological networks of BHD were built according to relationships among herbs, putative targets, and known therapeutic targets for ischemic stroke, and 121 major nodes were identified by calculating three topological features-degree, node betweenness, and closeness. Importantly, the pathway enrichment analysis identified several signaling pathways involved with major putative targets of BHD, such as the calcium signaling pathway, vascular smooth muscle contraction, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, which have not hitherto been reported. These data are expected to help find new therapeutic effects of BHD and optimize clinical use of this formula. Collectively, our study developed a comprehensive systems approach integrating drug target prediction and network and functional analyses to reveal the relationships of the herbs in BHD with their putative targets, and for the first time with ischemic stroke-related pathway systems. This is a pilot study based on bioinformatics analysis; thus, further experimental studies are required to validate our findings.