Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation


Дәйексөз келтіру

Толық мәтін

Аннотация

Introduction:Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data.

Materials and Methods:The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC.

Results:FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinic data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69.

Conclusion:Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

Авторлар туралы

Youwen Hu

Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University

Email: info@benthamscience.net

Yangyang Xiao

Department of Gerontology, Jiangxi University of Traditional Chinese Medicine Affiliated Hospital

Email: info@benthamscience.net

Lijun Wan

Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University

Email: info@benthamscience.net

Zhili Wen

Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74(3): 229-63. doi: 10.3322/caac.21834 PMID: 38572751
  2. Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019; 380(15): 1450-62. doi: 10.1056/NEJMra1713263 PMID: 30970190
  3. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76(3): 681-93. doi: 10.1016/j.jhep.2021.11.018 PMID: 34801630
  4. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018; 391(10127): 1301-14. doi: 10.1016/S0140-6736(18)30010-2 PMID: 29307467
  5. Huang J, Guo W, Cheung F, Tan HY, Wang N, Feng Y. Integrating network pharmacology and experimental models to investigate the efficacy of coptidis and scutellaria containing Huanglian Jiedu decoction on hepatocellular carcinoma. Am J Chin Med 2020; 48(1): 161-82. doi: 10.1142/S0192415X20500093 PMID: 31964157
  6. Chen Q, Shu C, Laurence AD, et al. Effect of Huaier granule on recurrence after curative resection of HCC: A multicentre, randomised clinical trial. Gut 2018; 67(11): 2006-16. doi: 10.1136/gutjnl-2018-315983 PMID: 29802174
  7. Yuan S, Gong Y, Chen R, Du J, Zhang H, Chen T. Chinese herbal formula QHF inhibits hepatocellular carcinoma metastasis via HGF/c-Met signaling pathway. Biomed Pharmacother 2020; 132: 110867. doi: 10.1016/j.biopha.2020.110867 PMID: 33075668
  8. General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer (2022 edition). J Clin Hepatol 2022; 38(2): 288-303. doi: 10.3969/j.issn.1001-5256.2022.02.009
  9. Liu Y, Li Y, Wang X, et al. Fufang Banmao capsule, A traditional Chinese medicinal formulation, enhances the survival of patients with hepatocellular carcinoma and Vp3-4 portal vein tumor thrombosis undergoing supportive treatment. J Altern Complement Med 2020; 26(10): 956-65. doi: 10.1089/acm.2019.0334 PMID: 32614605
  10. Liu X, Li M, Wang X, et al. Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma. Phytomedicine 2019; 62: 152930. doi: 10.1016/j.phymed.2019.152930 PMID: 31128485
  11. Hopkins AL. Network pharmacology. Nat Biotechnol 2007; 25(10): 1110-1. doi: 10.1038/nbt1007-1110 PMID: 17921993
  12. Hopkins AL. Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol 2008; 4(11): 682-90. doi: 10.1038/nchembio.118 PMID: 18936753
  13. He J, Qian Y, Yin Y, Kang J, Pan T. Polydatin: A potential NAFLD therapeutic drug that regulates mitochondrial autophagy through SIRT3-FOXO3-BNIP3 and PINK1-PRKN mechanisms - A network pharmacology and experimental investigation. Chem Biol Interact 2024; 398: 111110. doi: 10.1016/j.cbi.2024.111110 PMID: 38876248
  14. Jia R, Zheng H, Li S, et al. QingChang-XiaoPi decoction ameliorates intestinal inflammation of ulcerative colitis by regulating the pathogenicity of Th17 cells. Phytomedicine 2024; 132: 155779. doi: 10.1016/j.phymed.2024.155779 PMID: 38876011
  15. Hao J, Zhang X, Hu R, et al. Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling. J Transl Med 2024; 22(1): 555. doi: 10.1186/s12967-024-05355-9
  16. Li H, Wang R, Chen Y, et al. Integrated network pharmacology and pharmacological investigations to discover the active compounds of Toona sinensis pericarps against diabetic nephropathy. J Ethnopharmacol 2024; 333: 118441. doi: 10.1016/j.jep.2024.118441 PMID: 38851471
  17. Cai X, Kuerban M, Hasimu H, et al. Bioactive compounds from dichloromethane extract of Artemisia rupestris L. alleviates CCl4/ConA-induced acute liver injury by inhibiting PI3K-AKT pathway. J Ethnopharmacol 2024; 333: 118416. doi: 10.1016/j.jep.2024.118416 PMID: 38848975
  18. Fang S, Dong L, Liu L, et al. HERB: A high-throughput experiment and reference-guided database of traditional Chinese medicine. Nucleic Acids Res 2021; 49(D1): D1197-206. doi: 10.1093/nar/gkaa1063 PMID: 33264402
  19. Kim S, Chen J, Cheng T, et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res 2021; 49(D1): D1388-95. doi: 10.1093/nar/gkaa971 PMID: 33151290
  20. Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7: 42717. doi: 10.1038/srep42717
  21. Daina A, Zoete V. A BOILED-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 2016; 11(11): 1117-21. doi: 10.1002/cmdc.201600182 PMID: 27218427
  22. Wang X, Shen Y, Wang S, et al. PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res 2017; 45(W1): W356-60. doi: 10.1093/nar/gkx374 PMID: 28472422
  23. Clough E, Barrett T, Wilhite SE, et al. NCBI GEO: Archive for gene expression and epigenomics data sets: 23-year update. Nucleic Acids Res 2024; 52(D1): D138-44. doi: 10.1093/nar/gkad965 PMID: 37933855
  24. Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7. doi: 10.1089/omi.2011.0118 PMID: 22455463
  25. Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023; 51(D1): D638-46. doi: 10.1093/nar/gkac1000 PMID: 36370105
  26. Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498-504. doi: 10.1101/gr.1239303 PMID: 14597658
  27. Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell 2018; 173(2): 400-416.e11. doi: 10.1016/j.cell.2018.02.052 PMID: 29625055
  28. Han H, Cho JW, Lee S, et al. TRRUST v2: An expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 2018; 46(D1): D380-6. doi: 10.1093/nar/gkx1013 PMID: 29087512
  29. Bommareddy A, Brozena S, Steigerwalt J, et al. Medicinal properties of alpha-santalol, a naturally occurring constituent of sandalwood oil: Review. Nat Prod Res 2019; 33(4): 527-43. doi: 10.1080/14786419.2017.1399387 PMID: 29130352
  30. Tsai JJ, Pan PJ, Hsu FT, Chung JG, Chiang IT. Glycyrrhizic acid modulates apoptosis through extrinsic/intrinsic pathways and inhibits protein kinase B- and extracellular signal-regulated kinase- mediated metastatic potential in hepatocellular carcinoma in vitro and in vivo. Am J Chin Med 2020; 48(1): 223-44. doi: 10.1142/S0192415X20500123 PMID: 32054305
  31. An L, Zhang M, Lin Y, et al. Morroniside, a novel GATA3 binding molecule, inhibits hepatic stellate cells activation by enhancing lysosomal acid lipase expression. Phytomedicine 2022; 103: 154199. doi: 10.1016/j.phymed.2022.154199 PMID: 35679793
  32. Shi W, Feng L, Dong S, et al. FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1. Cell Commun Signal 2020; 18(1): 1-12. doi: 10.1186/s12964-020-00604-y
  33. Luo X, Zheng E, Wei L, et al. The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis. Cell Death Dis 2021; 12(4): 328. doi: 10.1038/s41419-021-03596-w

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