Molecular mechanism of action of Liuwei Dihuang pill for the treatment of osteoporosis based on network pharmacology and molecular docking

Liuwei Dihuang, a classic Chinese medicinal formula composed of six herbs, has been used to counteract functional decline due to aging and geriatric diseases such as osteoporosis. In this work we investigated the molecular mechanism of action of Liuwei Dihuang pill (LDP) in the treatment of osteoporosis through network pharmacology and molecular docking approaches. Combining data from the Network pharmacology platform of traditional Chinese Medicine, the active ingredients of LDP were screened. Targets prediction databases were used to predict the targets of LDP active ingredients. Osteoporosis-related targets were identified from databases of the disease. Target interaction networks were constructed, and analyzed by gene enrichment. Finally, the SystemsDOCK and POCASA was used to validate the affinity between the target and the active substance. We screened 99 ingredients of LDP and obtained 57 direct key target genes in the network. Gene annotation showed that the targets were involved mainly in 10 biological functions, such as muscle cell proliferation, anoikis, and reactive oxygen species metabolism. These results were confirmed by molecular docking, which identified 13 high-affinity active substances in LDP, including paeonol, cornudentanone, and alisol B. Our bioinformatic analyses suggest that LDP may be useful for the treatment of osteoporosis mainly by regulating proliferation and apoptosis signaling pathways, improving bone microenvironment, and regulating hormone and enzyme activities. Identification of some key target genes and active substances supports these results. These data provide a theoretical basis for further study of the role of LDP in the treatment of osteoporosis.