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CC BY 4.0 · Chinese medicine and natural products 2022; 02(02): e77-e88
DOI: 10.1055/s-0042-1755401
Original Article

Potential Mechanisms of Yanghe Decoction in the Treatment of Soft Tissue Sarcoma and Arteriosclerosis Obliterans Based on Network Pharmacology

Yiran Zhai
1   The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Shiqing Jiang
2   Department of Hematology and Oncology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Binyi Li
1   The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Lili Miao
1   The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Jie Wang
1   The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Shanshan Li
1   The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
› Author Affiliations Funding This study was supported by 2018 scientific and technological research projects in Henan Province (192102310430), Special Project of Chinese Medicine Research in Henan Province (2019ZYZD06)
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Abstract

Objective The objective of this study was to investigate potential mechanisms of Yanghe Decoction (, YHD) in treating soft tissue sarcoma (STS) and arteriosclerosis obliterans (ASO) based on the use of network pharmacology.

Methods Candidate compounds and potential targets were identified through the TCM Systems Pharmacology database and a comprehensive literature search. Related targets of STS and ASO were collected in the GeneCards database, DisGeNET database, and Drugbank database. Furthermore, The STRING 11.0 database was used to determine protein–protein interaction (PPI) networks; common targets were obtained and imported into Cytoscape 3.7.2. Then, a PPI network comprising common targets was drawn, and network topology analysis was performed to screen for key shared targets. Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key shared targets were performed by using Metascape software. Subsequently, a compound–target–pathway network was constructed via Cytoscape 3.7.2.

Results The following signaling pathways were found to be associated with the mechanisms of YHD in treating STS and ASO: AGE-RAGE signaling pathway, IL-17 signaling pathway; HIF-1 signaling pathway, TNF signaling pathway, interactions between cytokines and cytokine receptors, Th17 cell differentiation, and NOD-like receptor signaling pathway. Among the compounds and targets involved in these pathways, quercetin, luteolin, and kaempferol were found to be core compounds, and TNF, IL-6, and MAPK1 were found to be core targets.

Conclusion Taken together, our findings elucidated that potential mechanisms of YHD in treating STS and ASO involved cellular proliferation/differentiation, angiogenesis, inflammation, immune responses, oxidative stress, and other related signaling pathways.

Keywords

soft tissue sarcoma - arteriosclerosis obliterans - network pharmacology - Traditional Chinese medicine - Yanghe Decoction

Credit Authorship Contribution Statement

Yiran Zhai: Conceptualization, methodology, data curation, formal analysis, and writing original draft. Binyi Li and Lili Miao: Writing - review & editing. Shanshan Li and Jie Wang: Formal analysis. Shiqing Jiang: Conceptualization, methodology, and supervision.




Publication History

Received: 10 May 2021

Accepted: 29 June 2021

Article published online:
28 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Chinese Clinical Oncology Society Guidelines Working Committee. Chinese Clinical Oncology Society (CSCO) Guidelines for the Diagnosis and Treatment of Soft Tissue Sarcoma. Beijing: People's Medical Publishing House; 2019
    Google Scholar
  • 2 Vascular Surgery Group, Surgery Branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of arteriosclerosis obliterans of the lower extremities. Chin J Med Sci 2015; 95 (24) 1833-1896
    Google Scholar
  • 3 Wang Hl, Kang F, Huang X. Based on the theory of “Yang Huaqi, Yin Shaping” to discuss the application of warm-yang method in malignant tumors. Chin Basic Med Tradit Chin Med 2019; 25 (07) 999-1002
    Google Scholar
  • 4 Xu X, Wang S, Zhang MZ. et al. Clinical experience of professor Jiang Shiqing in prescribing Yang He decoction treating for soft tissue sarcoma. Acta Chin Med 2016; 31 (03) 319-321
    Google Scholar
  • 5 Fan HQ, Zhou L, Liu LF. et al. Based on the theory of “yang qi and yin shaping” to discuss the syndrome differentiation of yam and gangrene diseases. Chin J Basic Med Tradit Chin Med 2019; 25 (05) 685-686
    Google Scholar
  • 6 Wang ZQ, Qiao KM, Yu YN. et al. Cold and arteriosclerosis obliterans of lower extremities. J Tradit Chin Med 2017; 32 (04) 573-576
    Google Scholar
  • 7 Chen HB, Zhou HG, Li WT. et al. Network pharmacology: a new perspective of mechanism research of traditional Chinese medicine formula. Zhonghua Zhongyiyao Zazhi 2019; 34 (07) 2873-2876
    Google Scholar
  • 8 Tao JL, Wang SC, Chen YZ. et al. Review on the research in network pharmacology of traditional Chinese medicine compound. Zhonghua Zhongyiyao Zazhi 2019; 34 (09) 3903-3907
    Google Scholar
  • 9 Ru J, Li P, Wang J. et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6 (01) 13
    CrossrefPubMedGoogle Scholar
  • 10 Wang FU. Prescription Science. 2nd ed.. Beijing: China Traditional Chinese Medicine Publishing; 2012
    Google Scholar
  • 11 Zanini C, Giribaldi G, Mandili G. et al. Inhibition of heat shock proteins (HSP) expression by quercetin and differential doxorubicin sensitization in neuroblastoma and Ewing's sarcoma cell lines. J Neurochem 2007; 103 (04) 1344-1354
    CrossrefPubMedGoogle Scholar
  • 12 Shen M, Hang CT, Ping DQ. Targeting tumor ubiquitin-proteasome pathway with polyphenols for chemosensitization. Anti-Cancer Agents in Med Chem 2012;12(08):891–901.
  • 13 Lee DE, Chung MY, Lim TG, Huh WB, Lee HJ, Lee KW. Quercetin suppresses intracellular ROS formation, MMP activation, and cell motility in human fibrosarcoma cells. J Food Sci 2013; 78 (09) H1464-H1469
    CrossrefPubMedGoogle Scholar
  • 14 Choi YJ, Lee YH, Lee ST. Galangin and kaempferol suppress phorbol-12-myristate-13-acetate-induced matrix metalloproteinase-9 expression in human fibrosarcoma HT-1080 cells. Mol Cells 2015; 38 (02) 151-155
    CrossrefPubMedGoogle Scholar
  • 15 Huang SL, Hsu CL, Yen GC. Growth inhibitory effect of quercetin on SW 872 human liposarcoma cells. Life Sci 2006; 79 (02) 203-209
    CrossrefPubMedGoogle Scholar
  • 16 Iftikhar H, Rashid S. Molecular docking studies of flavonoids for their inhibition pattern against β-catenin and pharmacophore model generation from experimentally known flavonoids to fabricate more potent inhibitors for Wnt signaling pathway. Pharmacogn Mag 2014; 10 (38, Suppl 2) S264-S271
    CrossrefPubMedGoogle Scholar
  • 17 Choi JH, Kim KJ, Kim S. Comparative effect of quercetin and quercetin-3-O-β-d-glucoside on fibrin polymers, blood clots, and in rodent models. J Biochem Mol Toxicol 2016; 30 (11) 548-558
    CrossrefPubMedGoogle Scholar
  • 18 Choi JH, Kim YS, Shin CH, Lee HJ, Kim S. Antithrombotic activities of luteolin in vitro and in vivo. J Biochem Mol Toxicol 2015; 29 (12) 552-558
    CrossrefPubMedGoogle Scholar
  • 19 Choi JH, Park SE, Kim SJ, Kim S. Kaempferol inhibits thrombosis and platelet activation. Biochimie 2015; 115: 177-186
    CrossrefPubMedGoogle Scholar
  • 20 Zha KL, Li JF, Zeng Y. The role of SDF-1/CXCR 4 in the anti-atherosclerosis process of quercetin in Apo E−/− mice. Chongqing Yike Daxue Xuebao 2014; 39 (10) 1373-1379
    Google Scholar
  • 21 Lv L. Anti-Atherosclerosis Study of Quercetin Based on PI3K/Akt/NF-κb Signaling Pathway. Jilin University; 2017
    Google Scholar
  • 22 Ding X, Zheng L, Yang B, Wang X, Ying Y. Luteolin attenuates atherosclerosis via modulating signal transducer and activator of transcription 3-mediated inflammatory response. Drug Des Devel Ther 2019; 13: 3899-3911
    CrossrefPubMedGoogle Scholar
  • 23 Jean-Charles PY, Wu JH, Zhang L. et al. USP20 (ubiquitin-specific protease 20) inhibits TNF (tumor necrosis factor)-triggered smooth muscle cell inflammation and attenuates atherosclerosis. Arterioscler Thromb Vasc Biol 2018; 38 (10) 2295-2305
    CrossrefPubMedGoogle Scholar
  • 24 Lissat A, Joerschke M, Shinde DA. et al. IL6 secreted by Ewing sarcoma tumor microenvironment confers anti-apoptotic and cell-disseminating paracrine responses in Ewing sarcoma cells. BMC Cancer 2015; 15: 552
    CrossrefPubMedGoogle Scholar
  • 25 Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev 2014; 22 (03) 147-151
    CrossrefPubMedGoogle Scholar
  • 26 Murali R, Chandramohan R, Möller I. et al. Targeted massively parallel sequencing of angiosarcomas reveals frequent activation of the mitogen activated protein kinase pathway. Oncotarget 2015; 6 (34) 36041-36052
    CrossrefPubMedGoogle Scholar
  • 27 Otabe O, Kikuchi K, Tsuchiya K. et al. MET/ERK2 pathway regulates the motility of human alveolar rhabdomyosarcoma cells. Oncol Rep 2017; 37 (01) 98-104
    CrossrefPubMedGoogle Scholar
  • 28 Lee HS, Kim SD, Lee WM. et al. A noble function of BAY 11-7082: inhibition of platelet aggregation mediated by an elevated cAMP-induced VASP, and decreased ERK2/JNK1 phosphorylations. Eur J Pharmacol 2010; 627 (1-3): 85-91
    CrossrefPubMedGoogle Scholar
  • 29 Pott GB, Tsurudome M, Bamfo N, Goalstone ML. ERK2 and Akt are negative regulators of insulin and tumor necrosis factor-α stimulated VCAM-1 expression in rat aorta endothelial cells. J Inflamm (Lond) 2016; 13: 6
    CrossrefPubMedGoogle Scholar
  • 30 Yamagishi SI, Matsui T. Role of hyperglycemia-induced advanced glycation end product (AGE) accumulation in atherosclerosis. Ann Vasc Dis 2018; 11 (03) 253-258
    CrossrefPubMedGoogle Scholar
  • 31 Zhang X, Liu JY. Research progress of the anti-tumor effect of AGEs-RAGE system and metformin. Zhongguo Xin Yao Zazhi 2014; 23 (04) 441-444
    Google Scholar
  • 32 Robert M, Miossec P. Effects of interleukin 17 on the cardiovascular system. Autoimmun Rev 2017; 16 (09) 984-991
    CrossrefPubMedGoogle Scholar
  • 33 Guo MX, Zheng YJ, Tang B. et al. Expression of IL-17 signaling pathway related factor mRNA in esophageal tissue of esophageal cancer mice. J Zhengzhou Univ 2019; 54 (04) 492-495 (Med Sci)
    Google Scholar
  • 34 Wang XZ. Exploration of the interaction mechanism between IL-17 and Notch signaling pathway in pancreatic cancer. Beijing: Peking Union Medical College Publishing; 2017
    Google Scholar
  • 35 Zhang Cj, Yang Pr, Ma Y. New target for autoimmune diseases treatment: act1-mediated IL-17 signalling pathway. Immunol J 2012; 28 (05) 441-444
    Google Scholar
  • 36 Nyström H, Jönsson M, Werner-Hartman L, Nilbert M, Carneiro A. Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall. J Clin Pathol 2017; 70 (10) 879-885
    CrossrefPubMedGoogle Scholar
  • 37 Kouvaras E, Christoni Z, Siasios I, Malizos K, Koukoulis GK, Ioannou M. Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors. Biotech Histochem 2019; 94 (04) 283-289
    CrossrefPubMedGoogle Scholar
  • 38 Jain T, Nikolopoulou EA, Xu Q, Qu A. Hypoxia inducible factor as a therapeutic target for atherosclerosis. Pharmacol Ther 2018; 183: 22-33
    CrossrefPubMedGoogle Scholar
  • 39 Zhou W, Yin M, Cui H. et al. Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis. Eur Rev Med Pharmacol Sci 2015; 19 (18) 3375-3384
    PubMedGoogle Scholar
  • 40 Huang Y, Tao Y, Li X. et al. Bioinformatics analysis of key genes and latent pathway interactions based on the anaplastic thyroid carcinoma gene expression profile. Oncol Lett 2017; 13 (01) 167-176
    CrossrefPubMedGoogle Scholar
  • 41 Jiang X, Hao Y. Analysis of expression profile data identifies key genes and pathways in hepatocellular carcinoma. Oncol Lett 2018; 15 (02) 2625-2630
    PubMedGoogle Scholar
  • 42 Ma Y, Guan RJ. Research progress of stromal cell derived factor1 and its receptor 4 and atherosclerosis. Chin J Evid Based Cardiovasc Med 2013; 5 (05) 323-324
    Google Scholar
  • 43 Lin QW, Zhang S, Lu WQ. Research progress of NOD-like signaling pathways and the relationship between NOD and tumor. China Oncol 2019; 29 (03) 223-228
    Google Scholar
  • 44 Zhu M, He QH. Research progress of the role of Chinese medicine in autoimmune inflammatory diseases by regulating Th17 cell differentiation. J Hunan Univ Tradit Chin Med 2019; 36 (08) 82-86
    Google Scholar