国际口腔医学杂志

国际口腔医学杂志 ›› 2025, Vol. 52 ›› Issue (6): 771-782.doi: 10.7518/gjkq.2025063

• 论著 • 上一篇    下一篇

复方丹参滴丸治疗口腔扁平苔藓的潜在靶标

张逸之(),史雪珂,吴芳龙,周红梅()   

  1. 口腔疾病防治全国重点实验室 国家口腔医学中心 国家口腔疾病临床医学研究中心口腔医学+前沿医学创新中心 四川大学华西口腔医院 成都 610041
  • 收稿日期:2024-06-16 修回日期:2025-02-18 出版日期:2025-11-01 发布日期:2025-10-23
  • 通讯作者: 周红梅
  • 作者简介:张逸之，硕士，Email：zhangyizhi1@stu.scu.edu.cn
  • 基金资助:
    国家自然科学基金(82071124);国家自然科学基金(82301095);四川大学华西口腔医院探索与研发项目(RD-03-202410)

Potential targets of compound Danshen dripping pill in the treatment of oral lichen planus based on network pharmacology and molecular docking

Yizhi Zhang(),Xueke Shi,Fanglong Wu,Hongmei Zhou()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2024-06-16 Revised:2025-02-18 Online:2025-11-01 Published:2025-10-23
  • Contact: Hongmei Zhou
  • Supported by:
    National Natural Science Foundation of China(82071124);Research and Develop Program, West China Hospital of Stomatology Sichuan University(RD-03-202410)

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摘要：

目的 联合网络药理学及分子对接技术预测复方丹参滴丸治疗口腔扁平苔藓（OLP）的潜在靶标。 方法 于中药系统药理学数据库和分析平台获得药物活性成分及其作用靶点，通过DisGeNET等数据库获得OLP相关疾病靶点，得到共同靶点。构建药物-成分-靶点网络和蛋白质互作网络图，筛得关键成分和关键靶点。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析确定主要功能和通路。将关键活性成分和关键靶点分子对接并将结果可视化。 结果 获得469个药物-疾病共同靶点，药物关键成分为乙酸龙脑酯、丹参新醌D和丹参醇A，关键靶点为蛋白激酶B（AKT1）、腺病毒E1A 结合蛋白p300（EP300）和雌激素受体1（ESR1）等。GO结果提示，共同靶点涉蛋白质丝氨酸/苏氨酸激酶活性、炎症与信号传导等。KEGG富集通路包括，癌症相关通路和糖尿病并发症AGE-RAGE通路等。分子对接结果示，AKT1、哈维鼠肉瘤病毒（HRAS）与3个关键成分结合能均≤-5.0 kcal/mol。 结论 复方丹参滴丸中乙酸龙脑酯等活性成分可作用于AKT1、HRAS等靶点，进而调控癌症、AGE-RAGE等相关通路等来调节免疫功能、减少氧化应激和抑制炎症，促进OLP愈合。

关键词: 口腔扁平苔藓, 复方丹参滴丸, 网络药理学, 作用靶标, 分子对接

Abstract:

Objective This study aimed to forecast the potential targets of compound Danshen dripping pill (CDDP) in treating oral lichen planus OLP (OLP) via network pharmacology and molecular docking. Methods The active compounds and targets of CDDP were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The disease targets of OLP were obtained from multiple databases, such as DisGeNET. A drug-compound-target network was constructed by intersecting the targets to screen the key active components. A protein-protein interaction network was also built by intersecting the targets to select the key ones. Target intersection was also applied for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The molecular docking and visualization of key active components and targets were also performed. Results A total of 469 drug-disease intersecting targets were found. The key active components were bornyl acetate, dan-shexinkum D, and danshenol A, and the key targets were protein kinase B (AKT1), E1A binding protein p300 (EP300), and estrogen receptor 1 (ESR1). GO enrichment analysis indicated that the results of intersection targets included protein serine/threonine kinase activity, inflammatory response, signal transduction. KEGG enrichment analysis revealed various pathways such as cancer and AGE-RAGE signaling pathway in diabetic complications. Molecular docking showed that the results of AKT1, Harvey rat sarcoma virus (HRAS), and the three key active components were all ≤-5.0 kcal/mol. Conclusion In OLP treatment, the active components of CDDP may participate in immune function, reduce oxidative stress, inhibit inflammation by acting on multiple targets such as AKT1 and HRAS, and regulate pathways including cancer and AGE-RAGE signaling pathway.

Key words: oral lichen planus, compound Danshen dripping pill, network pharmacology, drug target, molecular docking

中图分类号: 

  • R78

表 1

CDDP组成药物的部分活性成分"

药物分子编码英文名称中文名称结构图口服生物利用度/%药物相似性
丹参*MOL007064przewalskin b(1R,4R,10R,13R)-13-羟基-5,5-二甲基-15-丙烷-2-基-11-氧酸四环[8.6.0.01,13.04,9]十六烷-8,15-二烯-12,14-二酮110.320.44
MOL007132

(2R)-3-(3,4-dihydroxyphenyl)-2-

[(Z)-3-(3,4-dihydroxyphenyl) acry-

loyl] oxy-propionic acid

(2R)-3-(3,4-二羟基苯基)-2-[(Z)-3-(3,4-二羟基苯基)丙烯酰基]氧代丙酸109.380.35
MOL007140

(Z)-3-[2-[(E)-2-(3,4-dihydroxyph-

nyl) vinyl]-3,4-dihydroxy-phenyl]

acrylic acid

(Z)-3-[2-[(E)-2-(3,4-二羟基苯烯)乙烯基]-3,4-二羟基苯基]丙烯酸88.540.26
MOL007150

(6S)-6-hydroxy-1-methyl-6-meth

lol-8,9-dihydro-7H-naphtho[8,7-g]

benzofuran-10,11-quinone

丹参二醇A75.390.46
MOL007058formyltanshinone醛基丹参酮73.440.42
MOL007120miltionone Ⅱ丹参酚醌Ⅱ71.030.44
MOL007105epidanshenspiroketallactone表丹参螺缩酮内脂68.270.31
MOL007155(6S)-6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[8,7-g]b-enzofuran-10,11-dione(6S)-6-(羟甲基)-1,6-二甲基-8,9-二氢-7H-萘[8,7-g]苯并呋喃-10,11-二酮65.260.45
MOL007130prolithospermic acid原紫草酸64.370.31
MOL0070502?(4-hydroxy-3-methoxyphenyl)?5-(3-hydroxypropyl)?7-methoxy-3-be-nzofurancarboxaldehyde2-(4-羟基-3-甲氧基苯基)-5-(3-羟丙基)-7-甲氧基-1-苯并呋喃-3-甲醛62.780.40
三七MOL000098quercetin槲皮素46.430.28
MOL000449stigmasterol豆甾醇43.830.76
MOL002879diop邻苯二甲酸二异辛酯43.590.39
MOL001494Mandenol亚麻油酸乙酯42.000.19
MOL000358beta-sitosterolβ-谷甾醇36.910.75
MOL007475ginsenoside f2人参皂苷f236.430.25
MOL005344ginsenoside rh2人参皂苷Rh236.320.56
MOL001792DFV甘草素32.760.18
冰片MOL006862bronyl acetate乙酸龙脑酯59.300.51
MOL006865dipterocarpol龙脑香醇酮41.710.76
MOL006861asiatic acid积雪草酸41.380.71

图 1

OLP相关靶点韦恩图"

图 2

OLP疾病靶点与药物交集靶点韦恩图OLP疾病靶点与CDDP药物作用靶点取交集得到469个靶点。"

图 3

药物-活性成分-靶点网络图"

图 4

基于STRING数据库构建的PPI网络图"

图 5

关键靶点筛选网络图A：初步构建PPI网络后，根据度中心性二倍中位数筛选靶点（黄色）；B：根据度中心性、中介中心性、接近中心性中位数再次筛选靶点（绿色）；C：根据度中心性二倍中位数选出核心靶点（红色），D：最后得到10个核心靶点，颜色根据度中心性增大由浅至深。"

图 6

GO及KEGG富集分析气泡图A：GO生物过程分析；B：GO细胞组分分析；C：GO分子功能分析；D：KEGG富集分析；左侧纵坐标对应不同GO/KEGG注释，右侧纵坐标-log10（P值）从红色到蓝色表示数值从小到大，横坐标Gene Ratio代表该词条的基因数占所有基因的比例。Count代表富集到此词条的基因数目，数目越多，气泡越大。每个类别仅列出排名前10（按P值由小到大排序）的条目。"

表 2

关键活性成分与关键靶点的分子对接结合能 (kcal/mol)"

关键靶点关键活性成分
乙酸龙脑酯丹参新醌D丹参醇A
AKT1-5.59-8.2-7.58
EP300-4.61-7.750.89
ESR1-4.29-6.870.89
HRAS-6.60-8.57-6.68
PIK3CA-5.28+0.60-6.76
PIK3CB-4.48-6.27-6.31
PIK3CD-4.07-6.97-6.32
PIK3R1-2.43-0.530.89
PTPN11-4.32-7.27-6.48
STAT3-3.40+0.60-5.24

图7

部分关键活性成分与关键靶点的分子对接图A：AKT1-Danshenol A对接2D图；B：HRAS-bronyl acetate对接2D图；C：HRAS-dan-shexinkum D对接2D图；D：AKT1-Danshenol A对接3D图；E：HRAS-bronyl acetate对接3D图；F：HRAS-dan-shexinkum D对接3D图；氢键长度单位为?。"

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