墨旱莲—女贞子治疗牙周炎的潜在成分及作用机制

doi:10.7518/hxkq.2025.2025049

华西口腔医学杂志 ›› 2025, Vol. 43 ›› Issue (5): 696-710.doi: 10.7518/hxkq.2025.2025049

墨旱莲—女贞子治疗牙周炎的潜在成分及作用机制

郭梦茹¹(), 张天翼², 黄靖雯², 黄莘越¹, 郑义²(), 张莉¹()

^1.吉林大学口腔医院急诊科，长春 130021
^2.吉林大学口腔医院牙周科，长春 130021

收稿日期:2025-02-12 修回日期:2025-05-14 出版日期:2025-10-01 发布日期:2025-10-21
通讯作者: 郑义,张莉 E-mail:Guomr23@mails.jlu.edu.cn;zhengyi8304@jlu.edu.cn;zhang_li99@jlu.edu.cn
作者简介:郭梦茹，住院医师，硕士，E-mail：Guomr23@mails.jlu.edu.cn
基金资助:
吉林省科技发展计划项目(YDZJ202301ZYTS013);吉林省教育厅科学技术研究项目(JJKH20250203KJ)

Mechanism of Eclipta prostrata L-Ligustrum lucidum Ait in the treatment of periodontitis

Guo Mengru¹(), Zhang Tianyi², Huang Jingwen², Huang Xinyue¹, Zheng Yi²(), Zhang Li¹()

^1.Dept. of Emergency, Hospital of Stomatology, Jilin University, Changchun 130021, China
^2.Dept. of Periodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China

Received:2025-02-12 Revised:2025-05-14 Online:2025-10-01 Published:2025-10-21
Contact: Zheng Yi,Zhang Li E-mail:Guomr23@mails.jlu.edu.cn;zhengyi8304@jlu.edu.cn;zhang_li99@jlu.edu.cn
Supported by:
Jilin Province Science and Technology Development Plan Project(YDZJ202301ZYTS013);Scientific Research Project of Education Department of Jilin Province(JJKH20250203KJ)

摘要/Abstract

摘要：

目的使用网络药理学与分子对接技术，探讨墨旱莲-女贞子（EPL-LLA）治疗牙周炎的潜在靶点和分子机制，并通过体外实验探究其生物相容性、对炎症相关因子的调控及抗氧化作用。方法通过多种数据库筛选并预测EPL-LLA的活性成分和潜在靶点，将其与牙周炎相关靶点取交集，通过STRING数据库构建蛋白质相互作用网络（PPI）。利用Metascape数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。将节度点值前6的药物活性成分与通过PPI筛选出的核心靶点进行分子对接，并将结合能较好的结果进行可视化分析。建立体外细胞模型，通过细胞计数试剂盒（CCK-8）、实时定量聚合酶链反应（qRT-PCR）和2,7-二氯二氢荧光素二乙酸酯（DCFH-DA）荧光探针，探究EPL-LLA的生物相容性、对炎症因子的调控作用及抗氧化作用。结果经筛选，EPL含有13种活性成分，对应220个潜在靶点；LLA含有10种活性成分，对应283个潜在靶点；牙周炎相关靶点1 643个；三者共有91个交集靶点。交集靶点经GO和KEGG富集分析，共筛选出5 271个条目和253条信号通路。分子对接结果证实节度点值前6的药物活性成分与核心靶点能够较好地结合。CCK-8实验显示浓度在0.02 mg/mL内的EPL-LLA具有良好的生物相容性（P<0.05）；qRT-PCR显示EPL-LLA降低牙龈卟啉单胞菌脂多糖（LPS）刺激后巨噬细胞促炎因子mRNA的表达，同时上调抑炎因子mRNA的表达（P<0.05）；利用DCFH-DA荧光探针检测证实EPL-LLA具有清除活性氧（ROS）的能力（P<0.05）。结论 EPL-LLA可通过多成分、多靶点、多通路治疗牙周炎，为进一步研究其对牙周炎的治疗提供了理论依据。

关键词: 牙周炎, 墨旱莲, 女贞子, 网络药理学, 分子对接, 巨噬细胞, 炎症因子, 氧化应激

Abstract:

Objective This study aimed to explore the potential target and molecular mechanism of Eclipta prostrata L-Ligustrum Lucidum Ait (EPL-LLA) in the treatment of periodontitis by using network pharmacology and molecular docking technology, and to explore its biocompatibility, regulatory effects on inflammatory factors, and antioxidant acti-vity through in vitro experiments. Methods The active components and potential targets of EPL-LLA were screened and predicted through a variety of databases, and the intersection of EPL-LLA and periodontitis targets was selected. The protein interaction network (PPI) was analyzed by the string platform. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The active ingredients from the top 6 degrees were docked with the core targets, and the results of binding energy were visualized. An in vitro cell model was established to evaluate the biocompatibility, modulation of inflammatory factors, and antioxidative effects of EPL-LLA through cell counting kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe assays. Results Screening revealed 13 active components in EPL corresponding to 220 potential targets, 10 active components in LLA corresponding to 283 potential targets, and 1 643 periodontitis-related targets, with 91 shared targets among the three. GO analysis of the shared targets yielded 5 271 entries, while KEGG enrichment analysis indicated involvement in 253 signaling pathways. Molecular docking confirmed stable binding between the top 6 active components and core targets. CCK-8 assays demonstrated good biocompatibility of EPL-LLA at concentrations 0.02 mg/mL (P<0.05). qRT-PCR showed that EPL-LLA reduced the mRNA expression of pro-inflammatory factors in macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS) while upregulating anti-inflammatory factor mRNA expression (P<0.05). DCFH-DA fluorescence probe assays confirmed the reactive oxygen species (ROS)-scavenging capacity of EPL-LLA (P<0.05). Conclusion EPL-LLA may treat periodontitis through multi-component, multi-target, and multi-pathway mechanisms, providing a theoretical basis for further research on its therapeutic potential.

Key words: periodontitis, Eclipta prostrata L, Ligustrum lucidum Ait, network pharmacology, molecular docking, macrophage, inflammatory factors, oxidative stress

中图分类号:

R781.4+2

郭梦茹, 张天翼, 黄靖雯, 黄莘越, 郑义, 张莉. 墨旱莲—女贞子治疗牙周炎的潜在成分及作用机制[J]. 华西口腔医学杂志, 2025, 43(5): 696-710.

Guo Mengru, Zhang Tianyi, Huang Jingwen, Huang Xinyue, Zheng Yi, Zhang Li. Mechanism of Eclipta prostrata L-Ligustrum lucidum Ait in the treatment of periodontitis[J]. West China Journal of Stomatology, 2025, 43(5): 696-710.

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参考文献 31

[1]	Priyamvara A, Dey AK, Bandyopadhyay D, et al. Periodontal inflammation and the risk of cardiovascular disease[J]. Curr Atheroscler Rep, 2020, 22(7): 28.
[2]	Hajishengallis G. Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications[J]. Periodontol 2000, 2022, 89(1): 9-18.
[3]	Mi L, Li JC, Hii ARK, et al. Dental cementum anchored microspheres embedded in a self-healing hydrogel for the antibacterial, anti-inflammation, osteogenic, and anti-osteoclastic management of periodontitis disease[J]. J Mater Chem B, 2024, 12(39): 9947-9962.
[4]	Huemer M, Mairpady Shambat S, Brugger SD, et al. Antibiotic resistance and persistence—implications for human health and treatment perspectives[J]. EMBO Rep, 2020, 21(12): e51034.
[5]	程成, 张薇, 朱波, 等. 中药抗常见耐药菌的作用及其机制研究进展[J]. 南京中医药大学学报, 2019, 35(2): 229-233.
	Cheng C, Zhang W, Zhu B, et al. Research progress on the effects and mechanisms of traditional Chinese medicine against common drug-resistant bacteria[J]. J Nanjing Univ Tradit Chin Med, 2019, 35(2): 229-233.
[6]	Zuo JY, Park C, Doschak M, et al. Are the release characteristics of Erzhi pills in line with traditional Chinese medicine theory? A quantitative study[J]. J Integr Med, 2021, 19(1): 50-55.
[7]	Cao CF, Sun XP. Herbal medicine for periodontal disea-ses[J]. Int Dent J, 1998, 48(3 ): 316-322.
[8]	Huang X, Shen H, Liu YR, et al. Fisetin attenuates perio-dontitis through FGFR1/TLR4/NLRP3 inflammasome pathway[J]. Int Immunopharmacol, 2021, 95: 107505.
[9]	Sczepanik FSC, Grossi ML, Casati M, et al. Periodon-titis is an inflammatory disease of oxidative stress: we should treat it that way[J]. Periodontol 2000, 2020, 84(1): 45-68.
[10]	Luo QQ, Ding JY, Zhu LP, et al. Hepatoprotective effect of wedelolactone against concanavalin A-induced liver injury in mice[J]. Am J Chin Med, 2018, 46(4): 819-833.
[11]	宋敏, 封安杰, 郭庆梅. 女贞子化学成分和药理作用研究进展及质量标志物的预测分析[J]. 中国药房, 2021, 32(24): 3064-3068.
	Song M, Feng AJ, Guo QM. Research progress on chemical constituents and pharmacological effects of ligustri lucidi fructus and predictive analysis on quality markers[J]. China Pharm, 2021, 32(24): 3064-3068.
[12]	Yu M, Shen Z, Zhang S, et al. The active components of Erzhi wan and their anti-Alzheimer’s disease mechanisms determined by an integrative approach of network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulation[J]. Heliyon, 2024, 10(13): e33761.
[13]	Peng MM, Xia TY, Zhong YM, et al. Integrative pharmacology reveals the mechanisms of Erzhi Pill, a traditio-nal Chinese formulation, against diabetic cardiomyopathy[J]. J Ethnopharmacol, 2022, 296: 115474.
[14]	Hopkins AL. Network pharmacology: the next paradigm in drug discovery[J]. Nat Chem Biol, 2008, 4(11): 682-690.
[15]	Liu JT, Liu CP, Chen HQ, et al. Tongguan capsule for treating myocardial ischemia-reperfusion injury: integrating network pharmacology and mechanism study[J]. Pharm Biol, 2023, 61(1): 437-448.
[16]	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.
[17]	Stelzer G, Rosen N, Plaschkes I, et al. The GeneCards suite: from gene data mining to disease genome sequen-ce analyses[J]. Curr Protoc Bioinformatics, 2016, 54: 1.30.1-1.30.33.
[18]	Zhou Y, Zhang YT, Zhao DH, et al. TTD: Therapeutic Target Database describing target druggability information[J]. Nucleic Acids Res, 2024, 52(D1): D1465-D1477.
[19]	Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased co-verage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res, 2019, 47(D1): D607-D613.
[20]	单梦丹, 钟应彬, 罗曼, 等. 基于网络药理学、分子对接及细胞实验验证探讨二至丸治疗多发性骨髓瘤的作用机制[J]. 广州中医药大学学报, 2024, 41(8): 2153-2161.
	Shan MD, Zhong YB, Luo M, et al. Exploration of the mechanism of Erzhi Wan in the treatment of multiple myeloma based on network pharmacology, molecular docking and cell experimental verification[J]. J Guangzhou Univ Tradit Chin Med, 2024, 41(8): 2153-2161.
[21]	宋子毅, 杨超, 张云龙, 等. 基于基因表达综合数据库芯片挖掘结合网络药理学与分子对接探讨芒果苷治疗口腔黏膜下纤维化的机制研究[J]. 华西口腔医学杂志, 2024, 42(4): 444-451.
	Song ZY, Yang C, Zhang YL, et al. Mechanism of mangiferin in the treatment of oral submucous fibrosis ba-sed on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking[J]. West China J Stomatol, 2024, 42(4): 444-451.
[22]	Wang ZK, Pu R, Zhang J, et al. Association between life’s essential 8 and periodontitis: evidence from NHA-NES 2009-2014[J]. Clin Oral Investig, 2024, 29(1): 37.
[23]	刘相, 康文燕, 商玲玲, 等. 西格列汀通过阻断核因子-κB信号通路抑制脂多糖诱导的人牙龈成纤维细胞炎症反应[J]. 华西口腔医学杂志, 2021, 39(2): 153-163.
	Liu X, Kang WY, Shang LL, et al. Sitagliptin inhibits lipopolysaccharide-induced inflammatory response in human gingival fibroblasts by blocking nuclear factor-κB signaling pathway[J]. West China J Stomatol, 2021, 39(2): 153-163.
[24]	Ma SJ, He HB, Ren XB, et al. Luteolin ameliorates pe-riodontitis by modulating mitochondrial dynamics and macrophage polarization via the JAK2/STAT3 pathway[J]. Int Immunopharmacol, 2025, 144: 113612.
[25]	Gómez-Florit M, Monjo M, Ramis JM. Identification of quercitrin as a potential therapeutic agent for periodontal applications[J]. J Periodontol, 2014, 85(7): 966-974.
[26]	Zhu HM, Cai C, Yu YK, et al. Quercetin-loaded bioglass injectable hydrogel promotes m6A alteration of Per1 to alleviate oxidative stress for periodontal bone defects[J]. Adv Sci (Weinh), 2024, 11(29): e2403412.
[27]	吴泽钰. 柚皮苷通过Akt/mTOR通路介导自噬促进牙槽骨成骨的作用及机制研究[D]. 乌鲁木齐: 新疆医科大学, 2023.
	Wu ZY. Effect and mechanism of naringin mediatingau-tophagy to promote alveolar boneosteogenesis through Akt/mTOR pathway[D]. Urumqi: Xinjiang Medical University, 2023.
[28]	Liu F, Huang X, He JJ, et al. Plantamajoside attenuates inflammatory response in LPS-stimulated human gingival fibroblasts by inhibiting PI3K/AKT signaling pathway[J]. Microb Pathog, 2019, 127: 208-211.
[29]	Ghosh-Choudhury N, Abboud SL, Nishimura R, et al. Requirement of BMP-2-induced phosphatidylinositol 3-kinase and Akt serine/threonine kinase in osteoblast differentiation and Smad-dependent BMP-2 gene transcription[J]. J Biol Chem, 2002, 277(36): 33361-33368.
[30]	Wang C, Liu C, Liang C, et al. Role of berberine thermosensitive hydrogel in periodontitis via PI3K/AKT pathway in vitro [J]. Int J Mol Sci, 2023, 24(7): 6364.
[31]	Gaillard T. Evaluation of AutoDock and AutoDock vina on the CASF-2013 benchmark[J]. J Chem Inf Model, 2018, 58(8): 1697-1706.

中文名称	英文名称	英文简写	身份标识号
B淋巴细胞瘤-2	B-cell lymphoma-2	BCL2	3B7O
肿瘤坏死因子	tumor necrosis factor	TNF	5M2J
缺氧诱导因子1α	hypoxia inducible factor-1α	HIF1A	3PXK
表皮生长因子受体	epidermal growth factor receptor	EGFR	1XKK
肿瘤蛋白p53	tumor protein P53	TP53	3LGF
雌激素受体1	estrogen receptor 1	ESR1	2BJ4
AKT丝氨酸/苏氨酸激酶1	AKT serine/threonine kinase 1	AKT1	1H10
核因子-κB1	nuclear factor kappa B1	NFκB1	4Q3J
基质金属蛋白酶9	matrix metalloproteinase 9	MMP9	1ITV
信号转导与转录激活因子3	signal transducer and activator of transcription 3	STAT3	5AX3

基因名称	引物序列（5’-3’）
β-actin	F：CTTTGCAGCTCCTTCGTTGC R：ACGATGGAGGGGAATACAGC
TNF-α	F：GGCAGGTCTACTTTGGAGTCATTG R：ACATTCGAGGCTCCAGTGAATTCGG
IL-6	F：CTGCAAGAGACTTCCATCCAG R：AGTGGTATAGACAGGTCTGTTGG
IL-1β	F：GAAATGCCACCTTTTGACAGTG R：TGGATGCTCTCATCAGGACAG
IL-10	F：GCTCTTACTGACTGGCATGAG R：CGCAGCTCTAGGAGCATGTG

项目	分子身份标识号码	活性成分	OB/%	DL/%
EPL活性成分	MOL001790	蒙花苷	39.84	0.70
	MOL001689	金合欢素	34.97	0.24
	MOL002975	紫铆因	69.93	0.21
	MOL003378	去甲蟛蜞菊内酯	33.93	0.43
	MOL003389	3’-O-甲基香豌豆苷元	57.40	0.27
	MOL003398	红车轴草素	39.06	0.27
	MOL003402	去甲基蟛蜞菊内酯	72.12	0.42
	MOL003404	蟛蜞菊内酯	49.60	0.47
	MOL000006	木犀草素	36.16	0.24
	MOL000098	槲皮素	46.43	0.27
LLA活性成分	MOL000358	β-谷甾醇	36.91	0.75
	MOL000422	山奈酚	41.88	0.24
	MOL004576	花旗松素	57.84	0.27
	MOL005146	Lucidumoside D	48.86	0.70
	MOL005147	Lucidumoside D_qt	54.40	0.47
	MOL005169	（20S）-24-ene-3β，20-diol-3-acetate	40.22	0.81
	MOL005190	圣草酚	71.79	0.24
	MOL005195	丁香脂素二葡萄糖苷	83.12	0.79
	MOL005209	光泽乌头碱	30.10	0.74
	MOL005211	黄麻属苷	65.45	0.22
	MOL005212	Olitoriside_qt	103.23	0.77
	MOL000006	木犀草素	36.16	0.24
	MOL000098	槲皮素	46.43	0.27

化合物	结合能/（kcal/mol）
化合物	BCL2	TNF	HIF1A	EGFR	TP53	ESR1	AKT1	NFκB1	MMP9	STAT3
紫铆亭	-8.5	-7.9	-6.9	-9.2	-8	-6.8	-8	-6.6	-10.5	-7.5
木犀草素	-8.5	-7.9	-6.9	-8.9	-7.6	-6.6	-8.2	-6.9	-10.9	-7.8
金合欢素	-7.9	-7.4	-7	-8.7	-7.3	-6.8	-7.9	-6.8	-10.5	-7.6
槲皮素	-7.6	-7.4	-7	-6.5	-7.3	-6.7	-7.9	-6.8	-9.8	-8.1
山柰酚	-7.5	-8.0	-6.9	-8.7	-6.9	-6.8	-7.7	-7.2	-10	-7.8
圣草酚	-7.9	-9.0	-6.9	-9.0	-7.8	-6.9	-8.2	-6.9	-11	-7.6

墨旱莲—女贞子治疗牙周炎的潜在成分及作用机制

Mechanism of Eclipta prostrata L-Ligustrum lucidum Ait in the treatment of periodontitis

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