Systems pharmacology approach to investigate the molecular mechanisms of herb Rhodiola rosea L. radix.

Rhodiola rosea L. radix (RRL) is one of the most popular medical herb which has been widely used for the treatment of different diseases effectively, including cardiovascular diseases and nerve system diseases. However, due to the multiple compounds in RRL, the underlying molecular mechanisms of RRL are remained unclear. To decipher the action mechanisms of RRL from a systematic perspective, a systems pharmacology approach integrated absorption, distribution, metabolism, and excretion (ADME) system, drug targeting, and network analysis was introduced. First, by the ADME screening system and the target fishing process, 56 potential active compounds and 62 targets were obtained, respectively. In addition, compound-target network demonstrated that most compounds interacted with multiple targets, indicating that RRL may enhance its therapeutic effects probably through hitting on multiple targets in a holistic level. Moreover, target-pathway network and gene ontology analysis showed that multiple targets of RRL were involved in several biological pathways, i.e. Neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling in cardiomyocytes, and VEGF signaling pathway, which dissecting the therapeutic effects of RRL on various diseases, such as cardiovascular diseases, depression, adaptation diseases, etc. In summary, this work successfully explains the potential active compounds and the multi-scale curative action mechanisms of RRL for treating various diseases; meanwhile, it implies that RRL could be applied as a novel therapeutic agent in arthritic diseases. Most importantly, this work provides an in silico strategy to understand the action mechanisms of herbal medicines from molecular/system levels, which will promote the new drug development of traditional Chinese medicine.