Objective  To investigate the regulatory mechanism of active components from Panax ginseng against triple-negative breast cancer (TNBC) using network pharmacology.

Methods  Active components of Panax ginseng and their corresponding targets were retrieved and collected from TCMSP and Swiss Target Prediction databases. TNBC-related targets were obtained from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized with Cytoscape software. Topological analysis within Cytoscape identified the top 10 core targets. DAVID was utilized for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the intersecting targets. Molecular docking validation between core components and key targets was performed using AutoDock Vina. Finally, 50 ns molecular dynamics (MD) simulations of the docked complex systems were conducted using Gromacs software.

Results  This study identified 56 active components of Panax ginseng and 753 associated targets. The intersection between Panax ginseng and TNBC yielded 277 common targets. Enrichment analysis revealed 1,377 significant GO terms and 166 KEGG pathways, primarily associated with pathways in cancer, the PI3K-Akt signaling pathway, and EGFR tyrosine kinase inhibitor resistance.

Conclusion The anti-TNBC effect of Panax ginseng exhibits multi-component, multi-target, and multi-pathway synergistic regulatory characteristics.

1.Yin L, Duan JJ, Bian XW, et al. Triple-negative breast cancer molecular subtyping and treatment progress[J]. Breast Cancer Res, 2020, 22(1): 61. DOI: 10.1186/s13058-020-01296-5.

2.Li Y, Zhang H, Merkher Y, et al. Recent advances in therapeutic strategies for triple-negative breast cancer[J]. J Hematol Oncol, 2022, 15(1): 121. DOI: 10.1186/s13045-022-01341-0.

3.杨珊, 赵暖暖, 杨鑫, 等. 人参活性成分及药理作用研究进展 [J]. 中医药导报, 2023, 29(1): 105-107. [Yang S, Zhao  NN, Yang X, et al. Research progress on active ingredients and pharmacological effects of Renshen (ginseng)[J]. Guiding Journal of Traditional Chinese Medicine and Pharmacology, 2023, 29(1): 105-107.] DOI: 10.13862/j.cn43-1446/r.2023.01.019.

4.王树明, 陈曦, 孙琦, 等. 人参的化学成分及药理作用研究进展[J]. 感染、炎症、修复, 2024, 25(3): 250-254. [Wang  SM, Chen X, Sun Q, et al. Progress in the study of chemical composition and pharmacological effects of ginseng[J]. Infection Inflammation Repair, 2024, 25(3): 250-254.] DOI: 10.3969/j.issn.1672-8521.2024.03.017.

5.姜丽, 张文彤, 肖彤, 等. 参苓白术散抗溃疡性结肠炎的物质基础、作用机制及安全性评价[J]. 武汉大学学报(理学版), 2024, 70(2): 236-252. [Jiang L, Zhang WT, Xiao T, et al. Progress on the material basis,mechanism of action and safety evaluation of Shenling Baizhu powder against ulcerative colitis[J]. Journal of Wuhan University (Natural Science Edition), 2024, 70(2): 236-252.] DOI: 10.14188/j.1671-8836.2023.0132.

6.Li M, Wang X, Wang Y, et al. Strategies for remodeling the tumor microenvironment using active ingredients of ginseng-a promising approach for cancer therapy[J]. Front Pharmacol, 2021, 12: 797634. DOI: 10.3389/fphar.2021.797634.

7.Peng H, Chen L, Deng Y, et al. Ginsenoside Rh2 mitigates myocardial damage in acute myocardial infarction by regulating pyroptosis of cardiomyocytes[J]. Clin Exp Hypertens, 2023, 45(1): 2229536. DOI: 10.1080/10641963.2023.2229536.

8.Yao ZW, Zhu H. Pharmacological mechanisms and drug delivery systems of ginsenoside Rg3: a comprehensive review[J]. Pharmacol Res, 2025, 216: 107799. DOI: 10.1016/j.phrs.2025.107799.

9.Jiang Z, Yang Y, Yang Y, et al. Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune[J]. Biomed Pharmacother, 2017, 96: 378-383. DOI: 10.1016/j.biopha.2017.09.129.

10.Valdés-González JA, Sánchez M, Moratilla-Rivera I, et al. Immunomodulatory, anti-inflammatory, and anti-cancer properties of ginseng: a pharmacological update[J]. Molecules, 2023, 28(9): 3863. DOI: 10.3390/molecules28093863.

11.Zhou H, Yan Y, Zhang X, et al. Ginseng polysaccharide inhibits MDA-MB-231 cell proliferation by activating the inflammatory response[J]. Exp Ther Med, 2020, 20(6): 229. DOI: 10.3892/etm.2020.9359.

12.邵琦, 李佳丽, 周李宁, 等. 人参炔醇重塑巨噬细胞表型调控乳腺癌细胞生物学行为[J]. 江苏大学学报(医学版), 2019, 29(4): 287-292. [Shao Q, Li JL, Zhou LN, et al. Effect of panaxynol on the biological behavior of breast cancer cells by remodeling macrophage phenotype[J]. Journal of Jiangsu University (Medicine Edition) , 2019, 29(4): 287-292.] DOI: 10.13312/j.issn.1671-7783.y190051.

13.韩利文, 陈善军, 董榕, 等. 网络药理学在中药复杂作用模式研究中的应用进展[J]. 山东科学, 2021, 34(6): 22-31. [Han LW, Chen SJ, Dong R, et al. Progress in the application of network pharmacology in the study of complex mode of action of traditional Chinese medicine[J]. Shandong Science, 2021, 34(6): 22-31.] DOI: 10.3976/j.issn.1002-4026.2021.06.004.

14.Derakhshan F, Reis-Filho JS. Pathogenesis of triple-negative breast cancer[J]. Annu Rev Pathol, 2022, 17: 181-204. DOI: 10.1146/annurev-pathol-042420-093238.

15.Zhou G, Wang CZ, Mohammadi S, et al. Pharmacological effects of ginseng: multiple constituents and multiple actions on humans[J]. Am J Chin Med, 2023, 51(5): 1085-1104. DOI: 10.1142/S0192415X23500507.

16.李丹, 鲍淑红. 基于网络药理学探讨人参对乳腺癌的作用机制[J]. 海南医学院学报, 2020, 26(6): 411-417. [Li D, Bao SH. Mechanism of ginseng against breast cancer based on network pharmacology[J]. Journal of Hainan Medical University, 2020, 26(6): 411-417.] DOI: 10.13210/j.cnki.jhmu.20200220.001.

17.Wang P, Song D, Wan D, et al. Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways[J]. Peer J, 2020, 8: e9281. DOI: 10.7717/peerj.9281.

18.Kaur S, Mendonca P, Soliman K. The anticancer effects and therapeutic potential of kaempferol in triple-negative breast cancer[J]. Nutrients, 2024, 16(15): 2392. DOI: 10.3390/nu16152392.

19.Li S, Yan T, Deng R, et al. Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1[J]. Onco Targets Ther, 2017, 10: 4809-4819. DOI: 10.2147/OTT.S140886.

20.Liu HX, Lian L, Hou LL, et al. Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1[J]. Animal Model Exp Med, 2024, 7(3): 234-258. DOI: 10.1002/ame2.12434.

21.Dong F, Qu L, Duan Z, et al. Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis[J]. Bioorg Chem, 2023, 135: 106537. DOI: 10.1016/j.bioorg.2023.106537.

22.Liu W, Yu Y, Hou T, et al. N-desmethyldauricine from menispermum dauricum DC suppresses triple-negative breast cancer growth in 2D and 3D models by downregulating the NF-κB signaling pathway[J]. Chem Biol Interact, 2024, 398: 111113. DOI: 10.1016/j.cbi.2024.111113.

23.Chatterjee A, Roy D, Guevara P, et al. Arachidonic acid induces the migration of MDA-MB-231 cells by activating raft-associated leukotriene B4 receptors[J]. Clin Cancer Drugs, 2018, 5(1): 28-41. DOI: 10.2174/2212697X05666180418145601.

24.Dibra D, Moyer SM, El-Naggar AK, et al. Triple-negative breast tumors are dependent on mutant p53 for growth and survival[J]. Proc Natl Acad Sci U S A, 2023, 120(34): e1986160176. DOI: 10.1073/pnas.2308807120.

25.史圆圆, 吴建农, 路名芝, 等. Akt1和ARK5在乳腺癌中的表达及临床病理意义[J]. 诊断病理学杂志, 2021, 28(3): 189-193. [Shi YY, Wu JN, Lu MZ, et al. Expression of Akt1 and ARK5 in breast cancer and its clinical significance[J]. Chinese Journal of Diagnostic Pathology, 2021, 28(3): 189-193.] DOI: 10.3969/j.issn.1007-8096.2021.03.006.

26.Kempska J, Oliveira-Ferrer L, Grottke A, et al. Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis[J]. Front Oncol, 2023, 13: 1129682. DOI: 10.3389/fonc.2023.1129682.

27.Livasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma[J]. Mod Pathol, 2006, 19(2): 264-271. DOI: 10.1038/modpathol.3800528.

28.朱清, 张光辉, 赵艳. STAT3蛋白在三阴性乳腺癌中的作用和临床病理意义[J]. 蚌埠医学院学报, 2022, 47(8): 994-998. [Zhu Q, Zhang GH, Zhao Y. Role and clinicopathological significance of STAT3 protein in triple-negative breast cancer[J]. Journal of Bengbu Medical University, 2022, 47(8): 994-998.] DOI: 10.13898/j.cnki.issn.1000-2200.2022.08.002.

29.Weinberg F, Peckys DB, de Jonge N. EGFR Expression in HER2-driven breast cancer cells[J]. Int J Mol Sci, 2020, 21(23): 9008. DOI: 10.3390/ijms21239008.

30.Roberts MR, Sucheston-Campbell LE, Zirpoli GR, et al. Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry[J]. Mol Carcinog, 2017, 56(3): 1000-1009. DOI: 10.1002/mc.22565.

31.Sriroopreddy R, Sudandiradoss C. Integrative network-based approach identifies central genetic and transcriptomic elements in triple-negative breast cancer[J]. Funct Integr Genomics, 2018, 18(2): 113-124. DOI: 10.1007/s10142-017-0579-3.

32.蒋国君, 刘亚明, 姚言雪, 等. SRC激酶在人乳腺癌细胞对阿霉素耐药及侵袭转移中的作用[J]. 四川大学学报(医学版), 2018, 49(5): 700-705. [Jiang GJ, Liu YM, Yao YX, et al. Effect of SRC kinase on adriamycin resistance and invasion and metastasis in human breast cancer cells[J]. Journal of Sichuan University (Medical Sciences), 2018, 49(5): 700-705.] DOI: 10.13464/j.scuxbyxb.2018.05.003.

33.Cruceriu D, Baldasici O, Balacescu O, et al. The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: molecular insights and therapeutic approaches[J]. Cell Oncol (Dordr), 2020, 43(1): 1-18. DOI: 10.1007/s13402-019-00489-1.

34.Chen B, Piel WH, Gui L, et al. The HSP90 family of genes in the human genome: insights into their divergence and evolution[J]. Genomics, 2005, 86(6): 627-637. DOI: 10.1016/j.ygeno.2005.08.012.

35.Cheng Q, Chang JT, Geradts J, et al. Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer[J]. Breast Cancer Res, 2012, 14(2): R62. DOI: 10.1186/bcr3168.

36.Mitobe Y, Iino K, Takayama KI, et al. PSF Promotes ER-positive breast cancer progression via posttranscriptional regulation of ESR1 and SCFD2[J]. Cancer Res, 2020, 80(11): 2230-2242. DOI: 10.1158/0008-5472.CAN-19-3095.

37.Deng Z, Ou M, Shi Y, et al. Ginsenoside Rg3 attenuates the stemness of breast cancer stem cells by activating the hippo signaling pathway[J]. Toxicol Appl Pharmacol, 2025, 494: 117158. DOI: 10.1016/j.taap.2024.117158.

38.James N, Owusu E, Rivera G, et al. Small molecule therapeutics in the pipeline targeting for triple-negative breast cancer: origin, challenges, opportunities, and mechanisms of action[J]. Int J Mol Sci, 2024, 25(11): 6285. DOI: 10.3390/ijms25116285.

39.Miricescu D, Totan A, Stanescu-Spinu II, et al. PI3K/AKT/mTOR signaling pathway in breast cancer: from molecular landscape to clinical aspects[J]. Int J Mol Sci, 2020, 22(1): 173. DOI: 10.3390/ijms22010173.

40.Revathidevi S, Munirajan AK. Akt in cancer: mediator and more[J]. Semin Cancer Biol, 2019, 59: 80-91. DOI: 10.1016/j.semcancer.2019.06.002.

41.Zhang HP, Jiang RY, Zhu JY, et al. PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer[J]. Breast Cancer, 2024, 31(4): 539-551. DOI: 10.1007/s12282-024-01567-5.

42.Prat A, Adamo B, Cheang MC, et al. Molecular characterization of basal-like and non-basal-like triple-negative breast cancer[J]. Oncologist, 2013, 18(2): 123-133. DOI: 10.1634/theoncologist.2012-0397.

43.Park HS, Jang MH, Kim EJ, et al. High EGFR gene copy number predicts poor outcome in triple-negative breast cancer[J]. Mod Pathol, 2014, 27(9): 1212-1222. DOI: 10.1038/modpathol.2013.251.

44.Zhang GN, Zhang YK, Wang YJ, et al. Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: in vitro and in vivo[J]. Cancer Lett, 2018, 424: 19-29. DOI: 10.1016/j.canlet.2018.02.040.

45.李石飞, 李欣萍, 刘文倩, 等. 基于网络药理学研究参芪扶正注射液调节免疫的作用机制[J]. 山西大学学报（自然科学版）, 2025, 48(2): 238-251. [Li SF, Li XP, Liu WQ, et al. The mechanism of Shenqi Fuzheng injection in regulating immunity based on network pharmacology[J]. Journal of Shanxi University (Natural Science Edition) , 2025, 48(2): 238-251.] DOI: 10.13451/j.sxu.ns.2024174.

46.王乐, 冯亚宏, 杜小利, 等. 基于网络药理学与分子对接探讨复方紫术栓治疗人乳头瘤病毒感染的作用机制[J/OL]. 医学信息, 2025-05-29. [Wang L, Feng YH, Du XL, et al. Mechanism of compound Zizhu suppository in treating HPV infection based on network pharmacology and molecular docking[J/OL]. Medical Information, 2025-05-29.] DOI: 10.7501/j.issn.1674-5515. 2023.11.008.

47.Zhang Z, Yu C, Wang H, et al. The history, beneficial ingredients, mechanism, processing, and products of Panax ginseng for medicinal and edible value[J]. Food Med Homol, 2025, 2: 9420059. DOI: 10.26599/FMH.2025.9420059.

48.李万丛, 艾芷伊, 游颖, 等. 人参多糖提取分析方法及生物活性研究进展[J]. 农产品加工, 2019, (10): 72-76. [Li WC, Ai  ZY, You  Y, et al. Research progress of extraction, analysis and bioactivities of ginseng polysaccharide[J]. Agricultural Products Processing, 2019, (10): 72-76.] DOI: 10.16693/j.cnki.1671-9646(X).2019.10.056.

49.Huang J, Liu D, Wang Y, et al. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy[J]. Gut, 2022, 71(4): 734-745. DOI: 10.1136/gutjnl-2020-321031.

50.Zhao J, Su C, Yang C, et al. Determination of ginsenosides Rb1, Rb2, and Rb3 in rat plasma by a rapid and sensitive liquid chromatography tandem mass spectrometry method: application in a pharmacokinetic study[J]. J Pharm Biomed Anal, 2012, 64-65: 94-97. DOI: 10.1016/j.jpba.2012.02.017.

51.谭珍媛, 熊万娜, 黄兴振, 等. 人参皂苷Rg1大鼠体内药代动力学及生物利用度研究[J]. 中药材, 2013, 36(7): 1121-1123. [Tan ZY, Xiong WN, Huang XZ, et al. Pharmacokinetics and bioavailability of ginsenoside Rg1 in rats[J]. Journal of Chinese Medicinal Materials, 2013, 36(7): 1121-1123.] DOI: 10.13863/j.issn1001-4454.2013.07.031.

52.Hu QR, Hong H, Zhang ZH, et al. Methods on improvements of the poor oral bioavailability of ginsenosides: pre-processing, structural modification, drug combination, and micro- or nano- delivery system[J]. J Ginseng Res, 2023, 47(6): 694-705. DOI: 10.1016/j.jgr.2023.07.005.

53.张淑红, 吴夏青, 王红娟, 等. 天然产物修复肠道屏障缓解溃疡性结肠炎的研究进展[J]. 中国病理生理杂志, 2025, 41(5): 1014-1023. [Zhang SH, Wu XQ, Wang HJ, et al. Progress in repair of intestinal barriers through treatments with natural products in ulcerative colitis[J]. Chinese Journal of Pathophysiology, 2025, 41(5): 1014-1023.] DOI: 10.3969/j.issn.1000-4718.2025.00.011.

54.陈若冰, 袁慎俊, 刘丹, 等. 人参皂苷Rg3抗肿瘤作用机制的研究新进展[J]. 生命的化学, 2017, 37(4): 561-565. [Chen RB, Yuan SJ, Liu D, et al. The new advance of reaserch on mechanism of antitumor action of ginsenoside Rg3[J]. Chemistry of Life, 2017, 37(4): 561-565. ] DOI: 10.13488/j.smhx.20170415.

55.杨森, 张晓娟, 张辰露. 人参皂苷CK活性及生物转化合成研究进展[J]. 广东化工, 2024, 51(15): 95-97. [Yang S, Zhang  XJ, Zhang CL. Research progress of ginsenoside CK activity and biotransformation synthesis[J]. Guangdong Chemical Industry, 2024, 51(15): 95-97.] DOI: 10.3969/j.issn.1007-1865.2024.015.033.