Abstract
BackgroundXianlinggubao formula (XLGB), a Chinese State Food and Drug Administration-permitted traditional Chinese herbal medicine, has been extensively used to treat osteoporosis. Although XLGB was shown to improve bone mass in ovariectomized rats and clinically alleviate osteoporosis symptoms, its pharmacological mechanisms remain unclear.MethodsIn this study, we used a network pharmacological approach to explore the potential mechanism of XLGB in treating osteoporosis. We obtained XLGB compounds from the TCMSP and TCMID databases and identified potential targets of these compounds through target fishing based on the TCMSP and Swiss Target Prediction databases. Next, we identified the osteoporosis targets by using the CTD, TTD, GeneCards, OMIM and PharmGKB databases. Then, the overlapping genes between the XLGB potential targets and the osteoporosis targets were used to establish a protein-protein interaction (PPI) network and to analyze their interactions and identify the major hub genes in this network. Subsequently, the Metascape database was utilized to conduct the enrichment of Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.ResultsThere were 104 active compounds and 295 related targets identified overall. After the Metascape enrichment analysis, we identified the top 25 cellular biological processes and top 15 pathways based on the logP value and found that the XLGB-mediated anti-osteoporosis effect was mainly associated with reactive oxygen species, organonitrogen compound response and cell migration. Furthermore, 36 hub genes of XLGB, such as EGF, EGFR, MTOR, MAPK14 and NFKB1, were considered potential therapeutic targets, suggesting the underlying mechanisms of XLGB acting on osteoporosis.ConclusionWe investigated the possible therapeutic mechanisms of XLGB from a systemic perspective. These key targets and pathways provide promising directions for future research to reveal the exact regulatory mechanisms of XLGB.
Highlights
Xianlinggubao formula (XLGB), a Chinese State Food and Drug Administration-permitted traditional Chinese herbal medicine, has been extensively used to treat osteoporosis
Active compounds of the XLGB capsules From the TCMSP and TCMID databases, we identified 553 related compounds in the formula, among which there were 130 ingredients (23.5%) in Yin Yang Huo (Epimedium sagittatum Maxim, Epimedium sagittatum maxim (YYH)), 202 (36.5%) in Dan Shen (Salvia miltiorrhiza Bunge, Salvia miltiorrhiza bunge (DS)), 76 (13.7%) in Di Huang (Rehmannia glutinosa Steud, Rehmannia glutinosa steud (DH)), 31 (5.6%) in (Dipsacus inermis Wall., Dipsacus inermis wall (XD)), 81 (14.6%) in Zhi Mu (Anemarrhena asphodeloides Bunge, Anemarrhena asphodeloides bunge (ZM)), and 33 (6.0%) in Bu Gu Zhi (Psoralea corylifolia L., BGZ)
We integrated the OP genes obtained from multisource databases, including CTD, GeneCards, TTD, OMIM and PharmGKB, and a total of 3601 related genes were identified After the construction of the Venn diagram, one hundred forty-six overlapping targets between the related targets of XLGB and OP were selected as the key targets through which XLGB exerts an anti-OP effect (Fig. 3)
Summary
Xianlinggubao formula (XLGB), a Chinese State Food and Drug Administration-permitted traditional Chinese herbal medicine, has been extensively used to treat osteoporosis. XLGB was shown to improve bone mass in ovariectomized rats and clinically alleviate osteoporosis symptoms, its pharmacological mechanisms remain unclear. Osteoporosis (OP) is a systemic bone disorder characterized by low bone mass and an accompanying increased incidences of fractures. Its treatment burden, $22 billion in 2008, is expected to rise due to the consistently increasing aging population. Related osteoporosis treatments should be used to alleviate or reduce symptoms such as fractures, which could result in substantial cost savings [2]. For inhibition of bone loss and maintenance of bone mass, antiresorptive agents, anabolic agents and bone mineral drugs have been widely used in clinical treatment [3]. The development of alternative and safe intervention strategies for osteoporosis is needed
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