Network pharmacological study and in vitro studies validation-Molecular dynamics simulation of Cistanche deserticola in promoting periodontitis and bone remodeling.

Autor: Shan C; Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumqi 830054, People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China., Wu Z; Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumqi 830054, People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China., Xia Y; Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumqi 830054, People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China., Ji X; Department of Prosthodontics and Dental Implantology, Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumgi 830054,People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China., Zhang W; Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumqi 830054, People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China., Peng X; State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address: pengx@scu.edu.cn., Zhao J; Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University (The Affiliated Stomatology Hospital of Xinjiang Medical University), No. 137 South Liyushan Road, Urumqi 830054, People's Republic of China; Xinjiang Uygur Autonomous Region Clinical Research Center for Oral Diseases, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China; Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, No.137 South Liyushan Road, Urumqi 830054, People's Republic of China. Electronic address: zhaojin@xjmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Jun 30; Vol. 135, pp. 112299. Date of Electronic Publication: 2024 May 21.
DOI: 10.1016/j.intimp.2024.112299
Abstrakt: Objective: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches.
Methods: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components.
Results: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 μg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 μg/ mL, 10 μg/ mL, and 100 μg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 μg/mL. Network pharmacology results revealed the network relationship between Cd's components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds.
Conclusion: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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