Original Articles

Network pharmacology-based analysis of the antithrombotic clinical efficacy and antithrombotic mechanism of Huoxue Jiedu prescription (活血解毒方) in the treatment of polycythemia vera with heat toxin and blood stasis syndrome

  • Yumin ZHAO ,
  • Yuliang ZHANG ,
  • Guozi WANG ,
  • Xizan LIU ,
  • Pengmin ZHAO ,
  • Mengjun ZHAO ,
  • Zhaoxia LI ,
  • Haixia DI
Expand
  • 1 College of Graduate Studies, Hebei North University, Zhangjiakou 075000, China
    2 4th Hematology Department, Langfang Hospital of Traditional Chinese Medicine, Langfang 065000 China
    3 Medical Department, Second Hospital of Zhangjiakou, Zhangjiakou 075000, China
    4 4th Hematology Department, Langfang Hospital of Traditional Chinese Medicine, Langfang 065000 China
    5 College of Graduate Studies, Hebei North University, Zhangjiakou 075000, China

Received date: 2024-07-12

  Accepted date: 2024-10-28

  Online published: 2025-11-24

Supported by

Scientific Research Project of the Chinese Society of Ethnographic Medicine: A Feasibility Study on the Treatment of Polycythemia Vera with Stasis-Expelling Decoctions Based on the Theory of Activating Blood and Resolving Stasis(2020, 2020ZY175-440801);Scientific Research Project of the Chinese Society of Traditional Chinese Medicine: a Real-World Prospective Study on the Use of Stasis-Expelling Decoctions in Treating Polycythemia Vera(2021, 202169-003);National Administration of Traditional Chinese Medicine Yang Shulian’s National Famous Traditional Chinese Medicine Expert Inheritance Studio Construction Project (State Administration of Traditional Chinese Medicine Jiaohan [2022] No. 75);Hebei Province Graduate Innovation Funding Project(2023, PX-19221895);Beijing-Tianjin-Hebei Traditional Chinese Medicine Collaborative Specialty Alliance (Hebei Traditional Chinese Medicine [2024] No. 11)

Abstract

OBJECTIVE: To explore the clinical efficacy and potential mechanisms of Huoxue Jiedu prescription (活血解毒方) in the treatment of polycythemia vera and provide objective basis for the treatment of polycythemia vera by using network pharmacology, molecular docking technology, and clinical trials.

METHODS: First, network pharmacology and molecular docking analysis methods were used to screen the main targets of Huoxue Jiedu prescription in the treatment of polycythemia vera. Patients who were first diagnosed with polycythemia vera in the Hematology Department of Langfang Hospital of Traditional Chinese Medicine from September 2022 to January 2024 were enrolled, and a clinical randomized controlled study was conducted. Sixty patients with primary polycythemia who met the inclusion criteria were randomly divided into the treatment group and the control group, with 30 cases in each group. The control group received oral Western Medicine treatment, whereas the treatment group received oral Western Medicine combined with Huoxue Jiedu prescription treatment, and three courses were observed. The differences in the efficacy of Traditional Chinese and Western Medicine, hematological indicators, coagulation function, and expression of related targets before and after treatment were observed between the two groups. SPSS 26.0 statistical software was used for data analysis, and the treatment results of the two groups were compared to observe their clinical efficacy and mechanisms.

RESULTS: Network pharmacology results identified the phosphatidyqinositol-3 kinase (PI3K-Akt) pathway as an important pathway of Huoxue Jiedu prescription in the treatment of polycythemia veraPV, which was closely related to thrombosis. Clinical trial results showed that Huoxue Jiedu prescription improved efficacy and hematological indicators, reduced patients’ coagulation indicators such as D-dimer and fibrinogen, reduced activated partial thromboplastin time and prothrombin time, and decreased the expression of PI3K and Serine/threonine-protein kinase AKT1 (AKT1) mRNA in peripheral blood.

CONCLUSION: Network pharmacology predicted the corresponding targets of traditional Chinese medicine to a certain extent. Huoxue Jiedu prescription could enhance clinical efficacy, improve hematological indicators, and reduce coagulation indicators through antithrombotic effect by inhibiting the expression of PI3K and AKT1.

Cite this article

Yumin ZHAO , Yuliang ZHANG , Guozi WANG , Xizan LIU , Pengmin ZHAO , Mengjun ZHAO , Zhaoxia LI , Haixia DI . Network pharmacology-based analysis of the antithrombotic clinical efficacy and antithrombotic mechanism of Huoxue Jiedu prescription (活血解毒方) in the treatment of polycythemia vera with heat toxin and blood stasis syndrome[J]. Journal of Traditional Chinese Medicine, 2025 , 45(6) : 1353 -1365 . DOI: 10.19852/j.cnki.jtcm.2025.06.014

References

1. Anderson LA, McMullin MF. Epidemiology of MPN: what do we know? Curr Hematol Malig Rep 2014; 9: 340-9.
2. Titmarsh GJ, Duncombe AS, McMullin MF, et al. How common are myeloproliferative neoplasms? A systematic review and Meta-analysis. Am J Hematol 2014; 89: 581-7.
3. Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013; 27: 1874-81.
4. Wehmeier A, Daum I, Jamin H, et al. Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. a retrospective analysis of 260 patients. Ann Hematol 1991; 63: 101- 6.
5. Berk PD, Goldberg JD, Donovan PB, et al. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol 1986; 23: 132-43.
6. Steinhubl SR, Bhatt DL, Brennan DM, et al. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med 2009; 150: 379- 86.
7. Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006; 367: 606-17.
8. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-94.
9. Su SB, Lu A, Li S, Jia W. Evidence-Based ZHENG: a Traditional Chinese Medicine syndrome. Evid Based Complement Alternat Med 2012; 2012: 246538.
10. Yu H, Chen J, Xu X, et al. A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PLoS One 2012; 7: e37608.
11. Burley SK, Bhikadiya C, Bi C, et al. RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. Nucleic Acids Res 2021; 49: D437-51.
12. Leukemia and Lymphoma Group of the Hematology Branch of the Chinese Medical Association. Chinese guidelines for diagnosis and treatment of polycythemia vera (2022 Edition). Zhong Hua Xue Ye Xue Za Zhi 2022; 43: 537-41.
13. Di HX, Liu XZ, Wang GZ, Zhang YL, Li YZ. Expert consensus on the diagnosis and treatment of polycythemia vera using integrated Traditional Chinese and Western Medicine (2022). Zhong Guo Zhong Xi Yi Jie He Za Zhi 2023; 43: 1-7.
14. Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia Vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood 2013; 121: 4778-81.
15. Zheng X. Guiding principles for clinical research of new Chinese medicines (Trial). Beijing: China Medical Science and Technology Press, 2002: 263-8.
16. Etti I, Abdullah R, Hashim NM, et al. Artonin E and structural Analogs from Artocarpus species abrogates estrogen receptor signaling in breast cancer. Molecules 2016; 21: 839.
17. Zhang N, Wang Y, An L, et al. Entropy drives the formation of salt bridges in the Protein GB3. Angew Chem Int Ed Engl 2017; 56: 7601-4.
18. Wang WL, Wang WN, Wang SF, et al. "Schr?dinger Equation-Approximate Models-Core Concepts-Simple Applications”: constructing a logical framework and knowledge graph of atom and molecule structures. Da Xue Hua Xue 2024; 39: 338-43.
19. Arunan E, Mani D. Dynamics of the chemical bond: inter- and intra-molecular hydrogen bond. Faraday Discuss 2015; 177: 51-64.
20. Dai C, Chung IJ, Krantz SB. Increased erythropoiesis in polycythemia vera is associated with increased erythroid progenitor proliferation and increased phosphorylation of Akt/PKB. Exp Hematol 2005; 33: 152-8.
21. Liu Y, Yin HJ, Chen KJ. Effect of paeoniflorin and ligustrazine on the F-actin-induced platelet activation level and platelet gelsolin in vitro. Zhong Guo Zhong Xi Yi Jie He Za Zhi 2020; 40: 313-7.
22. Zhang K, Ma X, Han SY, et al. Ameliorative effect of Panax ginseng saponins combined with Salvia miltiorrhiza phenolic acids on hemorheological abnormality in rats with acute blood stasis. Zhong Guo Yao Li Xue Yu Du Li Xue Za Zhi 2012; 26: 641-5.
23. Wang MM, Xue M, Xu YG, et al. Panax notoginseng saponin is superior to aspirin in inhibiting platelet adhesion to injured endothelial cells through COX pathway in vitro. Thromb Res 2016; 141: 146-52.
24. Wang ZY, Wang X, Zhang DY, Hu YJ, Li S. Traditional Chinese Medicine network pharmacology: development in new era under guidance of network pharmacology evaluation method guidance. Zhong Guo Zhong Yao Za Zhi 2022; 47: 7-17.
25. Ding J, Shanshan M, Mengcheng C, Danying Z, Jin Y. Integrated network pharmacology and clinical study to reveal the effects and mechanisms of Bushen Huoxue Huatan decoction on polycystic ovary syndrome. Evid Based Complement Alternat Med 2022; 2022: 2635375.
26. Zhang P, Zhang D, Zhou W, et al. Network pharmacology: towards the artificial intelligence-based precision Traditional Chinese Medicine. Brief Bioinform 2023; 25: bbad518.
27. Li S, Zhang B. Traditional Chinese Medicine network pharmacology: theory, methodology and application. Chin J Nat Med 2013; 11: 110-20.
28. Wu DY, Deng Y, Hao J, Xu X. PI3K/AKT/mTORsignaling mediates baicalin-inhibited proliferation in hypertrophic scar fibroblast. Zhong Guo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao 2014; 30: 60-7.
29. Mercer J, Figg N, Stoneman V, Braganza D, Bennett MR. Endogenous p53 protects vascular smooth muscle cells from apoptosis and reduces atherosclerosis in ApoE knockout mice. Circ Res 2005; 96: 667-74.
30. Zhang Y, Yang X, Bian F, et al. TNF-α promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-κB and PPAR-γ. J Mol Cell Cardiol 2014; 72: 85-94.
31. Li Z, Wu X, Gu L, et al. Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis. Cell Death Dis 2017; 8: e2888.
32. Li T, Wang DJ, Xu YY, et al. Metformin regulates macrophage differentiation and inhibits formation of atherosclerosis by activating AMPK/ STAT3 pathway in mice. Zhong Guo Dong Mai Za Zhi 2022; 30: 287-94.
33. Laubach JP, Fu P, Jiang X, et al. Polycythemia vera erythroid precursors exhibit increased proliferation and apoptosis resistance associated with abnormal RAS and PI3K pathway activation. Exp Hematol 2009; 37: 1411-22.
34. Wang MM, Xue M, Yang L, et al. Chinese herbal compounds for supplementing Qi and activating blood circulation combined with dual antiplatelet drugs alleviated human umbilical vein endothelial cell injury and platelet adhesion via up-regulation of PI3K/Akt Pathway. Zhong Guo Zhong Xi Yi Jie He Za Zhi 2016; 36: 842-8.
35. Marx C, Novotny J, Salbeck D, et al. Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps. Blood 2019; 134: 1859-72.
36. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell 2017; 170: 605-35.
37. Chaperot L, Blum A, Manches O, et al. Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J Immunol 2006; 176: 248-55.
38. Mukherji A, Janbandhu VC, Kumar V. HBx protein modulates PI3K/Akt pathway to overcome genotoxic stress-induced destabilization of cyclin D1 and arrest of cell cycle. Indian J Biochem Biophys 2009; 46: 37-44.
Outlines

/