IndraLab

"Meanwhile, through the construction and analysis of the network, we obtained important targets for LDD and the potential biological processes and signaling pathways for the treatment of osteoporosis (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, endothelial cell proliferation, JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix)."

"Meanwhile, this study suggests that LDD can regulate some cytokines related to osteoporosis, such as TGF- β , INF, IGF, and calmodulin 1-monooxygenase, which are closely associated with the activation of osteoclasts. [ xref , xref ]."

"LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research."

"Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and β -catenin mRNA expression ( P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1."

"(1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and β -catenin mRNA expression ( P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1."

"Cluster 1 is mainly involved in several signaling pathways in osteoporosis (such as MAPK, PI3K, and JAK-STAT signaling pathway) and positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, endothelial cell proliferation, and neovascularization during bone remodeling."