1887

Abstract

Oxymatrine is a natural quinazine alkaloid extracted from and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.

Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.

The objective of this study was to assess the pharmacological mechanisms and targets of oxymatrine in relation to COVID-19 lung cancer.

Utilizing network pharmacology analysis, a selection of 2628 genes were identified as co-targets for both COVID-19 and lung cancer. Subsequently, a clinicopathological analysis was conducted by integrating RNA-Seq and clinical data obtained from the TCGA-LUAD lung cancer dataset, which was acquired from the official TCGA website. The identification of pharmacological targets for oxymatrine was accomplished through the utilization of various databases including Pharm mapper, SWISS Target prediction, and STITCH. These identified targets were further investigated for protein-protein interaction (PPI) using STRING, as well as for gene ontology (GO) and KEGG pathways.

The effects of oxymatrine on COVID-19-induced lung cancer were mediated by immune regulation, cytoprotection, antiviral, and anti-inflammatory activities, immune regulation, and control of related signalling pathways, including the formation of the neutrophil extracellular trap, phagosome, Toll-like receptor signalling pathway, apoptosis, proteoglycans in cancer, extracellular matrix disassembly, and proteolysis involved in cellular protein catabolism. Furthermore, important substances and genes like ALB, MMP3, MMP1, and TLR4 may affect how oxymatrine suppresses lung cancer/COVID-19 development.

To treat COVID-19 or lung cancer paired with COVID-19, oxymatrine may improve the therapeutic efficacy of current clinical antiviral medicines and immunotherapy.

Funding
This study was supported by the:
  • Local Science and Technology Projects Guided by the Central Government (Award No. 2021FRD05024)
    • Principle Award Recipient: LeLi
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001766
2023-10-19
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/72/10/jmm001766.html?itemId=/content/journal/jmm/10.1099/jmm.0.001766&mimeType=html&fmt=ahah

References

  1. Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res 2020; 7:11 [View Article] [PubMed]
    [Google Scholar]
  2. Cui X, Zhao Z, Zhang T, Guo W, Guo W et al. A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19). J Med Virol 2021; 93:1057–1069 [View Article] [PubMed]
    [Google Scholar]
  3. Dai M, Liu D, Liu M, Zhou F, Li G et al. Patients with cancer appear more vulnerable to SARS-CoV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov 2020; 10:783–791 [View Article] [PubMed]
    [Google Scholar]
  4. Luo J, Rizvi H, Preeshagul IR, Egger JV, Hoyos D et al. COVID-19 in patients with lung cancer. Ann Oncol 2020; 31:1386–1396 [View Article] [PubMed]
    [Google Scholar]
  5. Liang W, Guan W, Chen R, Wang W, Li J et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020; 21:335–337 [View Article] [PubMed]
    [Google Scholar]
  6. Passaro A, Bestvina C, Velez Velez M, Garassino MC, Garon E et al. Severity of COVID-19 in patients with lung cancer: evidence and challenges. J Immunother Cancer 2021; 9:e002266 [View Article] [PubMed]
    [Google Scholar]
  7. Huang K, Zhang P, Zhang Z, Youn JY, Wang C et al. Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol Ther 2021; 225:107843 [View Article] [PubMed]
    [Google Scholar]
  8. Lan X, Zhao J, Zhang Y, Chen Y, Liu Y et al. Oxymatrine exerts organ- and tissue-protective effects by regulating inflammation, oxidative stress, apoptosis, and fibrosis: from bench to bedside. Pharmacol Res 2020; 151:104541 [View Article] [PubMed]
    [Google Scholar]
  9. Wang Y-P, Zhao W, Xue R, Zhou Z-X, Liu F et al. Oxymatrine inhibits hepatitis B infection with an advantage of overcoming drug-resistance. Antiviral Res 2011; 89:227–231 [View Article] [PubMed]
    [Google Scholar]
  10. Wu XN, Wang GJ. Experimental studies of oxymatrine and its mechanisms of action in hepatitis B and C viral infections. Chin J Dig Dis 2004; 5:12–16 [View Article] [PubMed]
    [Google Scholar]
  11. Ding Y, Li N, Sun J, Zhang L, Guo J et al. Oxymatrine inhibits bocavirus MVC replication, reduces viral gene expression and decreases apoptosis induced by viral infection. Virol Sin 2019; 34:78–87 [View Article] [PubMed]
    [Google Scholar]
  12. Dai J-P, Wang Q-W, Su Y, Gu L-M, Deng H-X et al. Oxymatrine inhibits influenza A virus replication and inflammation via TLR4, p38 MAPK and NF-κB pathways. Int J Mol Sci 2018; 19:965 [View Article] [PubMed]
    [Google Scholar]
  13. Zhou W, Wu Y, Pan M, Liu D, Liu B. Proliferation and migration of lung cancer could be inhibited by oxymatrine through the regulation for miR-520/VEGF. Am J Chin Med 2019; 47:865–878 [View Article] [PubMed]
    [Google Scholar]
  14. Zhou G-Z, Shi Y-Y, Cui L-S, Li A-F, Wang Q-Q et al. Oxymatrine induces A549 human non‑small lung cancer cell apoptosis via extrinsic and intrinsic pathways. Mol Med Rep 2018; 17:1071–1076 [View Article] [PubMed]
    [Google Scholar]
  15. Li W, Yu X, Tan S, Liu W, Zhou L et al. Oxymatrine inhibits non-small cell lung cancer via suppression of EGFR signaling pathway. Cancer Med 2018; 7:208–218 [View Article] [PubMed]
    [Google Scholar]
  16. Jung YY, Shanmugam MK, Narula AS, Kim C, Lee JH et al. Oxymatrine attenuates tumor growth and deactivates STAT5 signaling in a lung cancer xenograft model. Cancers 2019; 11:49 [View Article] [PubMed]
    [Google Scholar]
  17. Ye J, Zou M-M, Li P, Lin X-J, Jiang Q-W et al. Oxymatrine and cisplatin synergistically enhance anti-tumor immunity of CD8+ T cells in non-small cell lung cancer. Front Oncol 2018; 8:631 [View Article] [PubMed]
    [Google Scholar]
  18. Wu K, Wei P, Liu M, Liang X, Su M. To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis. J Adv Res 2019; 20:43–50 [View Article] [PubMed]
    [Google Scholar]
  19. Fisher LD, Lin DY. Time-dependent covariates in the Cox proportional-hazards regression model. Annu Rev Public Health 1999; 20:145–157 [View Article] [PubMed]
    [Google Scholar]
  20. Su M, Guo C, Liu M, Liang X, Yang B. Therapeutic targets of vitamin C on liver injury and associated biological mechanisms: a study of network pharmacology. Int Immunopharmacol 2019; 66:383–387 [View Article] [PubMed]
    [Google Scholar]
  21. Pan Q, Zhou R, Su M, Li R. The effects of plumbagin on pancreatic cancer: a mechanistic network pharmacology approach. Med Sci Monit 2019; 25:4648–4654 [View Article] [PubMed]
    [Google Scholar]
  22. Xiao H, Qin X, Wan J, Li R. Pharmacological targets and the biological mechanisms of formononetin for Alzheimer’s disease: a network analysis. Med Sci Monit 2019; 25:4273–4277 [View Article] [PubMed]
    [Google Scholar]
  23. Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS et al. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc 2016; 11:905–919 [View Article] [PubMed]
    [Google Scholar]
  24. Freer PE. The impact of the COVID-19 pandemic on breast imaging. Radiol Clin North Am 2021; 59:1–11 [View Article] [PubMed]
    [Google Scholar]
  25. Qin C, Zhou L, Hu Z, Zhang S, Yang S et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71:762–768 [View Article] [PubMed]
    [Google Scholar]
  26. Khanmohammadi S, Rezaei N. Role of toll-like receptors in the pathogenesis of COVID-19. J Med Virol 2021; 93:2735–2739 [View Article] [PubMed]
    [Google Scholar]
  27. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal 2020; 10:102–108 [View Article] [PubMed]
    [Google Scholar]
  28. Sun Y, Wu C, Ma J, Yang Y, Man X et al. Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling. Exp Cell Res 2016; 347:274–282 [View Article] [PubMed]
    [Google Scholar]
  29. Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci 2017; 147:1–73 [View Article] [PubMed]
    [Google Scholar]
  30. Gelzo M, Cacciapuoti S, Pinchera B, De Rosa A, Cernera G et al. Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients. Sci Rep 2022; 12:1212 [View Article] [PubMed]
    [Google Scholar]
  31. Shi S, Su M, Shen G, Hu Y, Yi F et al. Matrix metalloproteinase 3 as a valuable marker for patients with COVID-19. J Med Virol 2021; 93:528–532 [View Article] [PubMed]
    [Google Scholar]
  32. Mittal R, Patel AP, Debs LH, Nguyen D, Patel K et al. Intricate functions of matrix metalloproteinases in physiological and pathological conditions. J Cell Physiol 2016; 231:2599–2621 [View Article] [PubMed]
    [Google Scholar]
  33. Scheau C, Badarau IA, Costache R, Caruntu C, Mihai GL et al. The role of matrix metalloproteinases in the epithelial-mesenchymal transition of hepatocellular carcinoma. Anal Cell Pathol 2019; 2019:9423907 [View Article] [PubMed]
    [Google Scholar]
  34. Zhang M, Xue Y, Chen H, Meng L, Chen B et al. Resveratrol inhibits MMP3 and MMP9 expression and secretion by suppressing TLR4/NF-κB/STAT3 activation in Ox-LDL-treated HUVECs. Oxid Med Cell Longev 2019; 2019:9013169 [View Article] [PubMed]
    [Google Scholar]
  35. Halim CE, Xinjing SL, Fan L, Bailey Vitarbo J, Arfuso F et al. Anti-cancer effects of oxymatrine are mediated through multiple molecular mechanism(s) in tumor models. Pharmacol Res 2019; 147:104327 [View Article] [PubMed]
    [Google Scholar]
  36. Deng N, Xie L, Li Y, Lin H, Luo R. Oxymatrine alleviates periodontitis in rats by inhibiting inflammatory factor secretion and regulating MMPs/TIMP protein expression1. Acta Cir Bras 2018; 33:945–953 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001766
Loading
/content/journal/jmm/10.1099/jmm.0.001766
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error