Study On Anti-osteoporosis Effect Of Traditional Chinese Medicine Based On A System-level Approach

With an ageing population, osteoporosis is a serious threat to human health. Epimedium has long been used to relieve osteoporosis in China, the estrogenic properties of the herb are conferred by several phytoestrogens. 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. The edible traditional Chinese medicine is not only food but also medicine, can provide good conditions for efficient and non-toxic drugs of the prevention and treatment of osteoporosis. 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. On the basis of this, edible traditional Chinese medicine that possessed the anti-osteoporosis activity were obtained by systems pharmacology combining with evaluation of the antioxidant and anti-osteoporosis activities of the extracts of fifteen edible traditional Chinese medicine.A total of 77 active components(26%) that possessed similar structural features to estrogen as determined using herb feature mapping were selected from 293 compounds of Epimedium. 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. A total of 361 compounds(24%) of 12 edible traditional Chinese medicine were selected from 1502 compounds of 15 edible traditional Chinese medicine as the active components. Among of them, 336 active components are associated with 11 targets of estrogenlike action of Epimedium by using molecular docking. The compound–target further displayed 12 edible traditional Chinese medicine have potential anti-osteoporosis activity. The results of the antioxidant and anti-osteoporosis activities indicated five extracts of three edible traditional Chinese medicine had favorable antioxidant activity and suppressed TRAP activity, including Et OH extract of Zanthoxylum Bungeanum Maxim., Et OH and H2 O extracts of Mentha Haplocalyx Brig., Et OH and H2 O extracts of Fructus Canarii. And they reduced the proliferation and TRAP activity of osteoclasts in a dose-dependent manner. Among them, three extracts had favorable inhibitory effects on proliferation and TRAP activity of osteoclast, including H2 O extract of Mentha Haplocalyx Brig., Et OH extract and H2 O extract of Fructus Canarii., which possessed the stronger anti-osteoporosis activity.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. Among 15 edible traditional Chinese medicine, the extracts from Fructus Canarii and Mentha Haplocalyx Brig. possessed the better antioxidant and antiosteoporosis activities, which have great application prospect for anti-osteoporosis in functional food and drug development. Moreover, it provided scientific basis for exploring hygienical function of anti-osteoporosis of edible traditional Chinese medicine.