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2026, 03, v.31 131-140
基于生物信息学、机器学习和网络药理学探究桑色素治疗牙周炎的作用机制研究
基金项目(Foundation): 新疆维吾尔自治区自然科学基金重点项目(2022D01D57); 新疆维吾尔自治区研究生创新项目(XJ2024G175); 新疆维吾尔自治区“天山英才”科技创新领军人才项目(2023TSYCLJ0032)
邮箱(Email): merryljin@sina.com;
DOI: 10.15956/j.cnki.chin.j.conserv.dent.2026.03.002
投稿时间: 2025-11-01
投稿日期(年): 2025
修回时间: 2025-12-05
终审时间: 2026-01-05
终审日期(年): 2026
审稿周期(年): 1
发布时间: 2026-03-28
出版时间: 2026-03-28
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摘要:

目的 采用生物信息学、网络药理学和机器学习技术探究桑色素治疗牙周炎的可能机制。方法 采用BATMAN-TCM 2.0、HERB等数据库收集桑色素靶点;通过Genecards、OMIM等数据库检索牙周炎相关基因,并结合GEO数据库筛选差异基因。免疫浸润分析牙周炎组织的炎症细胞表达。构建PPI网络、GO和KEGG富集,通过加权基因共表达网络和机器学习鉴定桑色素治疗牙周炎的核心靶标,利用分子对接验证桑色素与关键靶点的结合力。最后,采用体外细胞实验验证了桑色素改善炎症环境的作用机制。结果 共获得桑色素治疗牙周炎的潜在靶标72个。桑色素主要通过白细胞介素(IL)-17信号通路,作用于丝裂原活化蛋白激酶(MAPK)14和基质金属蛋白酶(MMP)-9等核心靶点治疗牙周炎。体外细胞实验表明,桑色素能够呈剂量依赖性抑制一氧化氮的释放以及肿瘤坏死因子(TNF-α)、IL-6、IL-1β炎症因子表达,这种抑制可能是通过抑制MAPK14、MMP-9表达调控IL-17通路改善炎症。结论 桑色素能够通过抑制MAPK14、MMP-9表达调控IL-17通路改善牙周炎。

Abstract:

Objective This study employed bioinformatics, network pharmacology, and machine learning techniques to explore the possible mechanism of morin in the treatment of periodontitis. Methods Morin targets were collected using databases such as BATMAN-TCM 2.0 and HERB; The genes related to periodontitis were searched for using databases such as Genecards and OMIM, and the differential genes were screened in combination with the GEO database. Immune infiltration analysis of inflammatory cell expression in periodontitis tissues. Construct PPI networks and GO and KEGG enrichment. Weighted gene co-expression networks and machine learning were used to identify the core targets of morin in the treatment of periodontitis, and molecular docking was employed to verify the binding force between morin and key targets. Finally, in vitro cell experiments were conducted to verify the mechanism by which morin improves the inflammatory environment. Results A total of 72 potential targets of morin for the treatment of periodontitis were obtained. Morin mainly treats periodontitis through core targets such as the IL-17 signaling pathway, MAPK14 and MMP-9. In vitro experiments have shown that morin can dose-dependently inhibit the release of NO and the expression of inflammatory factors such as TNF-α, IL-6, and IL-1β. This inhibition may be achieved by regulating the IL-17 pathway and improving inflammation by inhibiting the expression of MAPK14 and MMP-9. Conclusion Morin can regulate the IL-17 pathway by inhibiting the expression of MAPK14 and MMP-9 to improve periodontitis.

参考文献

[1]GBD 2021 Oral Disorders Collaborators. Trends in the global, regional,and national burden of oral conditions from 1990 to 2021:A systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet,2025,405(10482):897-910. DOI:10.1016/S0140-6736(24)02811-3.

[2]YU M, WU H, HU H, et al. Emerging near-infrared targeting diagnostic and therapeutic strategies for ischemic cardiovascular and cerebrovascular diseases[J]. Acta Biomater,2026,211:241-265. DOI:10.1016/j.actbio.2024.11.027.

[3]KWON T, LAMSTER IB, LEVIN L. Current concepts in the management of periodontitis[J]. Int Dent J,2021,71(6):462-476. DOI:10.1111/idj.12630.

[4]KHADEMI R, MIRZAEI A, MIRZAEI A, et al. Morin, as a natural flavonoid, provides promising influences against cardiovascular diseases[J]. Naunyn Schmiedebergs Arch Pharmacol,2025,398(6):6293-6310. DOI:10.1007/s00210-024-03783-4.

[5]夏娜,唐璐,李宇,等.牙周病患者口腔微生物菌群特征及其对TLRs信号通路及炎症因子水平的影响研究[J].实用口腔医学杂志,2025,41(4):495-500.DOI:10.3969/j.issn.1001-3733.2025.04.010

[6]XING A, WANG F, LIU J, et al. The prospect and underlying mechanisms of Chinese medicine in treating periodontitis[J]. Chin J Nat Med,2025,23(3):269-285. DOI:10.1016/S1875-5364(25)60842-9.

[7]LI H, LI L, YANG S, et al. Exploring the nonlinear relationship between dietary flavonoid intake and periodontitis[J]. Int Dent J,2025,75(2):716-726. DOI:10.1016/j.identj.2024.10.015.

[8]RAJPUT S A, WANG X Q, YAN H C. Morin hydrate:A comprehensive review on novel natural dietary bioactive compound with versatile biological and pharmacological potential[J]. Biomed Pharmacother, 2021,138:111511. DOI:10.1016/j.biopha.2021.111511.

[9]ARIYO O O, AJAYI A M, ATTAH F A, et al. Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf.(Moraceae)in rodents[J]. J Ethnopharmacol,2024,328:118112.DOI:10.1016/j.jep.2024.118112.

[10]WANG X, WANG Y, YUAN T, et al. Network pharmacology provides new insights into the mechanism of traditional Chinese medicine and natural products used to treat pulmonary hypertension[J]. Phytomedicine,2024,135:156062. DOI:10.1016/j.phymed.2024.106011.

[11]刘绍源,高茸,宋凡,等.基于网络药理学和分子对接技术探讨黄连解毒汤治疗心肌缺血再灌注损伤的分子机制[J].空军军医大学学报,2025,46(8):1081-1089,1096.DOI:10.13276/j.issn.2097-1656.2025.08.018.

[12]卢锦,黎芷诺,李朝晖,等.基于网络药理学与生物信息学分析探究染料木素治疗牙周炎的作用机制[J].空军军医大学学报, 2025,46(10):1275-1279.DOI:10.13276/j.issn.2097-1656.2025.10.003.

[13]KIM S, CHEN J, CHENG T, et al. PubChem in 2021:New data content and improved web interfaces[J]. Nucleic Acids Res,2021,49(D1):D1388-D1395. DOI:10.1093/nar/gkaa971.

[14]DAINA A, MICHIELIN O, ZOETE V. SwissTargetPrediction:Updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res, 2019,47(W1):W357-W364.DOI:10.1093/nar/gkz382.

[15]FANG S, DONG L, LIU L, et al. HERB:A high-throughput experiment-and reference-guided database of traditional Chinese medicine[J]. Nucleic Acids Res,2021,49(D1):D1197-D1206. DOI:10.1093/nar/gkaa1063.

[16]KONG X, LIU C, ZHANG Z, et al. BATMAN-TCM 2.0:An enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins[J].Nucleic Acids Res,2024,52(D1):D1110-D1120. DOI:10.1093/nar/gkad926.

[17]RU J, LI P, WANG J, et al. TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform,2014,6:13. DOI:10.1186/1758-2946-6-13.

[18]WANG X, SHEN Y, WANG S, et al. PharmMapper 2017 update:A web server for potential drug target identification with a comprehensive target pharmacophore database[J]. Nucleic Acids Res,2017,45(W1):W356-W360. DOI:10.1093/nar/gkx374.

[19]PIÑERO J, RAMÍREZ-ANGUITA JM, SAÜCH-PITARCH J, et al.The DisGeNET knowledge platform for disease genomics:2019 update[J]. Nucleic Acids Res,2020,48(D1):D845-D855. DOI:10.1093/nar/gkz1021.

[20]STELZER G, ROSEN N, PLASCHKES I, et al. The genecards suite:From gene data mining to disease genome sequence analyses[J]. Curr Protoc Bioinformatics,2016,54:1.30.1-1.30.33. DOI:10.1002/cpbi.5.

[21]AMBERGER J S, HAMOSH A. Searching online mendelian inheritance in man(OMIM):A knowledgebase of human genes and genetic phenotypes[J]. Curr Protoc Bioinformatics,2017,58:1.2.1-1.2.12.DOI:10.1002/cpbi.27.

[22]DEMMER R T, BEHLE J H, WOLF D L, et al. Transcriptomes in healthy and diseased gingival tissues[J]. J Periodontol,2008,79(11):2112-2124. DOI:10.1902/jop.2008.080139.

[23]KEBSCHULL M, DEMMER R T, GRÜN B, et al. Gingival tissue transcriptomes identify distinct periodontitis phenotypes[J]. J Dent Res,2014,93(5):459-468. DOI:10.1177/0022034514527288.

[24]GUAN X, WANG Y, LI W, et al. The role of macrophage efferocytosis in the pathogenesis of apical periodontitis[J]. Int J Mol Sci,2024,25(7):3854. DOI:10.3390/ijms25073854.

[25]MILLS KHG. IL-17 and IL-17-producing cells in protection versus pathology[J]. Nat Rev Immunol,2023,23(1):38-54. DOI:10.1038/s41577-022-00746-9.

[26]LUO Z, WANG H, WU Y, et al. Clinical significance of IL-23regulating IL-17A and/or IL-17F positive Th17 cells in chronic periodontitis[J]. Mediators Inflamm,2014,2014:627959. DOI:10.1155/2014/627959.

[27]MOHAMMED M A, ABBAS R F, AKRAM H M. Salivary IL-17 and IL-10 as potential diagnostic biomarkers of different stages of periodontitis in smoker and nonsmoker patients[J]. Eur J Dent,2024,18(1):253-264. DOI:10.1055/s-0043-1768154.

[28]ESPARBÈS P, LEGRAND A, BANDIAKY O N, et al. Subgingival microbiota and cytokines profile changes in patients with periodontitis:A pilot study comparing healthy and diseased sites in the same oral cavities[J]. Microorganisms,2021,9(11):2364.DOI:10.3390/microorganisms9112364.

[29]GRAVES D T, COCHRAN D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction[J]. J Periodontol,2003,74(3):391-401. DOI:10.1902/jop.2003.74.3.391.

[30]TEIXEIRA Q E, FERREIRA D C, DA SILVA A M P, et al. Aging as a risk factor on the immunoexpression of pro-inflammatory IL-1β,IL-6 and TNF-α cytokines in Chronic apical periodontitis lesions[J].Biology(Basel),2021,11(1):14. DOI:10.3390/biology11010014.

[31]RELVAS M, MENDES-FRIAS A, GONÇALVES M, et al. Salivary IL-1β, IL-6, and IL-10 are key biomarkers of periodontitis severity[J]. Int J Mol Sci,2024 ,25(15):8401. DOI:10.3390/ijms25158401.

[32]SUMBAYAK I A, MASULILI S L C, TADJOEDIN F M, et al.Changes in interleukin-1β, tumor necrosis factor-α, and interleukin-10 cytokines in older people with periodontitis[J]. Geriatrics(Basel),2023,8(4):79. DOI:10.3390/geriatrics8040079.

[33]VEERASUBRAMANIAN P K, WYNN T A, QUAN J, et al. Targeting TNF/TNFR superfamilies in immune-mediated inflammatory diseases[J]. J Exp Med,2024,221(11):e20240806. DOI:10.1084/jem.20240806.

[34]AZUMA M M, SAMUEL R O, GOMES-FILHO J E, et al. The role of IL-6 on apical periodontitis:A systematic review[J]. Int Endod J,2014,47(7):615-21. DOI:10.1111/iej.12196.

[35]MEHROTRA P, MASCHALIDI S, BOECKAERTS L, et al. Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair[J]. Nature,2024,631(8019):207-215. DOI:10.1038/s41586-024-07585-9.

[36]KIM W J, PARK S Y, KIM O S, et al. Autophagy upregulates inflammatory cytokines in gingival tissue of patients with periodontitis and lipopolysaccharide-stimulated human gingival fibroblasts[J]. J Periodontol,2022,93(3):380-391. DOI:10.1002/JPER.21-0178.

[37]WANG F, LONG S, ZHANG J.*Moringa oleifera*Lam. leaf extract safely inhibits periodontitis by regulating the expression of p38α/MAPK14-OPG/RANKL[J]. Arch Oral Biol,2021,132:105280. DOI:10.1016/j.archoralbio.2021.105280.

[38]ADAMOWICZ K, WANG H, JOTWANI R, et al. Inhibition of GSK3abolishes bacterial-induced periodontal bone loss in mice[J]. Mol Med,2012,18(1):1190-6. DOI:10.2119/molmed.2012.00180.

[39]REHANI K, WANG H, GARCIA CA, et al. Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2[J]. J Immunol,2009,182(1):547-53. DOI:10.4049/jimmunol.182.1.547.

[40]JANSSON L, LUNDMARK A, MODIN C, et al. Levels of matrix metalloproteinase-1(MMP-1), MMP-2, MMP-3, osteopontin,pentraxin-3, and thymic stromal lymphopoietin in crevicular fluid samples from peri-implantitis, periodontitis, and healthy sites[J]. J Periodontal Res,2025,60(5):473-483. DOI:10.1111/jre.13338.

[41]PAKPAHAN ND, KYAWSOEWIN M, MANOKAWINCHOKE J,et al. Intermittent compressive force regulates matrix metalloproteinases and tissue inhibitors of metalloproteinases expression in human periodontal ligament cells[J]. Arch Oral Biol,2024,165:106011. DOI:10.1016/j.archoralbio.2024.10.015.

[42]RATTANAPRUKSKUL K, XIA X J, JIANG M, et al. Molecular signatures of senescence in periodontitis:Clinical insights[J]. J Dent Res,2024,103(8):800-808. DOI:10.1177/00220345241255325.

基本信息:

DOI:10.15956/j.cnki.chin.j.conserv.dent.2026.03.002

中图分类号:R781.42

引用信息:

[1]连冰洁,黄文,吴泽钰,等.基于生物信息学、机器学习和网络药理学探究桑色素治疗牙周炎的作用机制研究[J].牙体牙髓牙周病学杂志,2026,31(03):131-140.DOI:10.15956/j.cnki.chin.j.conserv.dent.2026.03.002.

基金信息:

新疆维吾尔自治区自然科学基金重点项目(2022D01D57); 新疆维吾尔自治区研究生创新项目(XJ2024G175); 新疆维吾尔自治区“天山英才”科技创新领军人才项目(2023TSYCLJ0032)

投稿时间:

2025-11-01

投稿日期(年):

2025

修回时间:

2025-12-05

终审时间:

2026-01-05

终审日期(年):

2026

审稿周期(年):

1

发布时间:

2026-03-28

出版时间:

2026-03-28

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