Integrating network pharmacology and experimental evaluation to explore the complementary therapeutic effect and mechanism of melatonin in periodontitis
作者全名：Tuerhong, Kamoran; Liu, Kehao; Shen, Danfeng; Zhang, Qianyu; Huang, Qi; Yang, Mingcong; Huang, Ziyu; Wang, Lu; Yang, Sheng; Li, Yuzhou
作者地址：[Tuerhong, Kamoran; Liu, Kehao; Shen, Danfeng; Zhang, Qianyu; Huang, Qi; Yang, Mingcong; Huang, Ziyu; Wang, Lu; Yang, Sheng; Li, Yuzhou] Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China; [Wang, Lu; Yang, Sheng; Li, Yuzhou] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China
通信作者：Wang, L; Yang, S; Li, YZ (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China.
来源：HELIYON
ESI学科分类：
WOS号：WOS:001252388500001
JCR分区：Q1
影响因子：3.4
年份：2024
卷号：10
期号：12
开始页：
结束页：
文献类型：Article
关键词：Periodontitis; Melatonin; Network pharmacology analysis; Matrix metalloproteinases; Myeloperoxidase
摘要：Objective: To explore the potential targets for melatonin in the treatment of periodontitis through network pharmacologic analysis and experimental validation via in vivo animal models and in vitro cellular experiments. Materials and methods: In this study, we first screened melatonin targets from Pharm Mapper for putative targets, Drug Bank, and TCMSP databases for known targets. Then, disease database was searched and screened for differential expressed genes associated with periodontitis. The intersection of disease and melatonin-related genes yielded potential target genes of melatonin treatment for periodontitis. These target genes were further investigated by protein -protein interaction network and GO/KEGG enrichment analysis. In addition, the interactions between melatonin and key target genes were interrogated by molecular docking simulations. Then, we performed animal studies to validate the therapeutic effect of melatonin by injecting melatonin into the peritoneal cavity of ligation -induced periodontitis (LIP) mice. The effects of melatonin on the predicted target proteins were also analyzed using Western blot and immunofluorescence techniques. Finally, we constructed an in vitro cellular model and validated the direct effect of melatonin on the predicted targets by using qPCR. Results: We identified 8 potential target genes by network pharmacology analysis. Enrichment analysis suggests that melatonin may treat periodontitis by inhibiting the expression of three potential targets (MPO, MMP8, and MMP9). Molecular docking results showed that melatonin could effectively bind to MMP8 and MMP9. Subsequently, melatonin was further validated in a mouse LIP model to inhibit the expression of MPO, MMP8, and MMP9 in the periodontal tissue. Finally, we verified the direct effect of melatonin on the mRNA expression of MPO, MMP8, and MMP9 in an in vitro cellular model. Conclusions: Through a combination of network pharmacology and experimental validation, this study provides a more comprehensive understanding of the mechanism of melatonin to treat periodontitis. Our study suggests that MPO, MMP8, and MMP9 as key target genes of melatonin to treat periodontitis. These findings present a more comprehensive basis for further investigation into the mechanisms of pharmacological treatment of periodontitis by melatonin.
基金机构：National Natural Science Foundation of China [82171010]; Oral Restorative Biofilm Research Program of Young Clinical Research Fund of Chinese Dental Association [CSA-SIS2022-16]; Natural Science Foundation of Chongqing [CSTB2023NSCQ-MSX0615]
基金资助正文：YZ. L was supported by the National Natural Science Foundation of China (82001103) , Oral Restorative Biofilm Research Program of Young Clinical Research Fund of Chinese Dental Association (CSA-SIS2022-16) , and the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0925, KJQN202200434) . S. Y was supported by the National Natural Science Foundation of China (82171010) . DF. S was supported by the Natural Science Foundation of Chongqing (CSTB2023NSCQ-MSX0615) .
