Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach

Epimedium is a popular traditional herbal medicine worldwide that has long been used to relieve osteoporosis. The estrogenic properties of the herb are conferred by several phytoestrogens, such as flavonoids, lignans, and steroids. However, the poor understanding on the estrogen-like mechanism of Epimedium at the molecular and system levels limits the applications of this herb in osteoporosis treatment. In this study, systems pharmacology was established to investigate the relationship between Epimedium and estrogen against osteoporosis by integrating active component screening, drug-likeness evaluation, herb feature mapping, target prediction and validation, and network analysis. A total of 77 active components that possessed similar structural features to estrogen as determined using herb feature mapping were selected from Epimedium by oral bioavailability prediction and drug-likeness evaluation. Twenty three osteoporosis-related targets were obtained from the active components of Epimedium as potential targets, 11 of which were common targets with estrogen. All osteoporosis-related targets were further mapped to compound–target and target–pathway networks. Results displayed that Epimedium can exert anti-osteoporosis effects by directly regulating the 11 estrogen-related targets and a set of target proteins on five estrogen-related pathways. This study explained the estrogen-like mechanism of Epimedium in preventing and treating osteoporosis, and provided a new standpoint for exploring the traditional herbal medicine against osteoporosis.