Exploring the Mechanisms of Sanguinarine in the Treatment of
Osteoporosis by Integrating Network Pharmacology Analysis and Deep
Learning Technology

Yonghong      Tang; Daoqing      Zhou; Fengping      Gan; Zhicheng      Yao; Yuqing      Zeng

doi:10.2174/0115734099282231240214095025

Note! Please note that this article is currently in the "Article in Press" stage and is not the final "Version of record". While it has been accepted, copy-edited, and formatted, however, it is still undergoing proofreading and corrections by the authors. Therefore, the text may still change before the final publication. Although "Articles in Press" may not have all bibliographic details available, the DOI and the year of online publication can still be used to cite them. The article title, DOI, publication year, and author(s) should all be included in the citation format. Once the final "Version of record" becomes available the "Article in Press" will be replaced by that.

Abstract

Background: Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP).

Objective: This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP.

Methods: OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells.

Results: A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast.

Conclusion: CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

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DOI https://dx.doi.org/10.2174/0115734099282231240214095025	Print ISSN 1573-4099
Publisher Name Bentham Science Publisher	Online ISSN 1875-6697

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