Network Pharmacology-Based Analysis on the Action Mechanism of Oleanolic Acid to Alleviate Osteoporosis

Abstract

Oleanolic acid (OA) is a triterpenoid commonly found in plants and has shown extensive pharmaceutical activities. This study aimed to investigate the underlying mechanism of antiosteoporosis (OP) action of OA by utilizing the network pharmacology approach and molecular docking methods. First, the targets of OA were identified using the GeneCards, Stitch, and Swisstarget databases, and the targets related to OP were mined using the NCBI, Genecards, and DisGeNet databases. The overlapped targets of OA and OP were regarded as candidate targets, and the String database was used to obtain the protein− protein interactions among the targets. Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment pathways of the candidate targets were performed using the DAVID database. In addition, the top 16 targets in the protein interaction network were used for molecular docking. Finally, an animal model constructed using D-galactose-induced oxidative stress and a low-calcium diet with accelerated bone loss was used to verify the in vivo effects of OA on osteoporotic mice. A total of 42 candidate targets for OA to treat OP were obtained. According to the protein−protein interaction network, MAPK1 showed the highest connectivity with other proteins. Additionally, GO analysis identified the top 20 biological processes, 9 cellular components, and top 20 molecular functions. Moreover, the candidate targets were mainly involved in 13 signaling pathways such as TNF signaling pathway, insulin resistance, MAPK signaling pathway, apoptosis, and PI3K-Akt signaling pathways. Furthermore, molecular docking revealed that OA has a high degree of connections with 16 key proteins. In addition, the anti-OP effects of OA are further validated through the in vivo model. Altogether, our study elucidated the candidate targets for OA to alleviate OP, explored the protein−protein interactions and related signaling pathways of the targets, and validated the anti-OP effects of OA. It could provide a better understanding of the action mechanism in OA to treat OP.

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

“…Furthermore, GO analysis revealed that bosutinib mainly influences extracellular structure organization, extracellular matrix organization, sterol biosynthetic process, secondary alcohol biosynthetic process, and cholesterol biosynthetic process (Figure B). Pathways enrichment analysis using GO and KEGG revealed several pathways related with bone metabolism or bone-related disease, including extracellular matrix organization, steroid biosynthesis, TNF signaling pathway, as well as starch and sucrose metabolism. − PCA showed that the difference between groups is obvious (Figure S1D). Venn diagram analysis revealed that 382 and 297 genes were specifically expressed in hUCMSCs induced with and without bosutinib, respectively, with 10830 genes co-expressed between the two groups (Figure C).…”

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

“…OA proved useful in bone tissue regeneration by modulating Notch signaling and growth factor bone morphogenetic protein 2 (BMP2); the phytocompound induced mesenchymal stromal cell (MSC) osteogenic differentiation in a dose-dependent leading to the enhanced osteogenic proteins expressions of ALP, Runx2, and Collagen I, and subsequently stimulating bone formation [ 181 ]. Additionally, in vitro and in vivo studies showed that OA inhibited TNF-α, MAPK, and PI3-Akt signaling pathways, the results of which were further validated through molecular docking, leading to increased bone salt deposition and accelerated calcification, and hence to an improved bone architecture [ 182 ]. In contrast, having investigated OA bone protective effects in vivo in lipopolysaccharides-induced bone loss in mice, Zhao et al revealed that OA inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL) levels, but without influencing the RANKL-induced up-regulation of the NF-kB/Akt pathways.…”

Integrated metabolomics, network pharmacology, and molecular docking to reveal the mechanisms of Isodon excisoides against drug‐induced liver injury

“…The endogenous mechanisms underlying changes in metabolites are unclear. In recent years, network pharmacology has had an extensive applicational value in many fields, including the discovery of effective ingredients, drug–target identification, and research on mechanism of action (Y. Wu, Gao, et al, 2021). Rather than looking for a single causative gene or a drug acting on only a single target, network pharmacology considers the entire drug–disease network with the aim of finding multi‐target drugs (Gertsch, 2011).…”