AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025260279
Submit to EJMO
Cite this article
5
Download
39
Views
Related Info Links
Google Scholar
More by Authors Links
Ping Li
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

Research trends and visualization of cinobufagin in oncology treatment: A bibliometric analysis

Xiaoqin Li1† ,  Xueya Li1† ,  Ting Sun1 ,  Kexin Liu1 ,  Ting Wang1 ,  Rui Sheng1 ,  Ping Li1,2,3*
Show Less
1 Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
2 Department of Integrated Traditional Chinese and Western Medicine, School of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, Anhui, China
3 Graduate School, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
†These authors contributed equally to this work.
EJMO, 025260279 https://doi.org/10.36922/EJMO025260279
Received: 26 June 2025 | Revised: 11 September 2025 | Accepted: 12 September 2025 | Published online: 24 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Download PDF
XML
Cite
Abstract

Introduction: Cinobufagin shows promise in cancer therapy, particularly for hepatocellular carcinoma, with an emerging focus on survival outcomes and combination strategies.

Objective: This study employed bibliometric methods to analyze and visualize research trends and hotspots related to cinobufagin in oncology using CiteSpace (v.6.2) and VOSviewer (v.1.6.20).

Methods: Publications in Science Citation Index and Emerging Sources Citation Index journals indexed in the Web of Science database from inception to September 3, 2024, were retrieved. Visual analyses with CiteSpace and VOSviewer were conducted to identify co-cited authors, institutions, journals, countries, keywords, references, and research trends.

Results: Of 179 relevant English-language documents retrieved, 172 met the inclusion criteria after excluding conference abstracts, unpublished articles, duplicates, and irrelevant studies. The most prolific and cited authors were Inagaki Yoshinori, Kokudo Norihiro, and Tang Wei. Cancer Science had the highest total citations, while Shanghai University of Chinese Medicine was the leading research institution. China produced the largest number of publications. Co-cited literature mainly focused on cinobufagin’s pharmacological properties and anti-tumor mechanisms, particularly in hepatocellular carcinoma. Frequently used keywords included “cinobufagin toxin base,” “hepatocellular carcinoma,” “toad toxin,” “apoptosis,” and “gene expression.” Emerging hotspots highlight cinobufagin’s pharmacological activity and pharmacokinetics, mechanisms across multiple cancers, effects on patient survival, and potential synergy with chemotherapy.

Conclusion: This study mapped research trends on cinobufagin in cancer therapy, emphasizing its role in tumor cell cycle inhibition and signaling pathways. Key research areas include hepatocellular carcinoma, colon cancer, and lung cancer, with a growing focus on survival outcomes. Safety, side effects, and risk management strategies remain critical areas for future research.

Keywords
Cinobufaginm
Bibliometrics
Visual analysis
Anti-tumour mechanism
Chinese medicine
Funding
This study was funded by the Collaborative Innovation Project of Colleges and Universities in Anhui Province of China (Grant number: 9021706203).
Conflict of interest
The authors report no conflicts of interest in this work.
References
  1. Dai CL, Zhang RJ, An P, Deng YQ, Rahman K, Zhang H. Cinobufagin: a promising therapeutic agent for cancer. J Pharm Pharmacol. 2023;75(9):1141-1153. doi: 10.1093/jpp/rgad059

 

  1. Zhang H, Jian B, Kuang H. Pharmacological Effects of Cinobufagin. Med Sci Monit. 2023;29. doi: 10.12659/msm.940889

 

  1. Ninkov A, Frank JR, Maggio LA. Bibliometrics: Methods for studying academic publishing. Perspect Med Educ. 2021;11(3):173-176. doi: 10.1007/s40037-021-00695-4

 

  1. Roldan-Valadez E, Salazar-Ruiz SY, Ibarra-Contreras R, Rios C. Current concepts on bibliometrics: a brief review about impact factor, Eigenfactor score, CiteScore, SCImago Journal Rank, Source-Normalised Impact per Paper, H-index, and alternative metrics. Ir J Med Sci. 2018;188(3):939-951. doi: 10.1007/s11845-018-1936-5

 

  1. van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2009;84(2):523-538. doi: 10.1007/s11192-009-0146-3

 

  1. Zyoud SH, Smale S, Waring WS, Sweileh WM, Al-Jabi SW. Global research trends in microbiome-gut-brain axis during 2009–2018: a bibliometric and visualized study. BMC Gastroenterol. 2019;19(1). doi: 10.1186/s12876-019-1076-z

 

  1. Zhang L, Zheng H, Jiang ST, et al. Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis. Int J Surg. 2024;110(3):1699-1710. doi: 10.1097/js9.0000000000001022

 

  1. Chen C, Hu Z, Liu S, Tseng H. Emerging trends in regenerative medicine: a scientometric analysis in CiteSpace. Expert Opin Biol Ther. 2012;12(5):593-608. doi: 10.1517/14712598.2012.674507

 

  1. Pei Z, Chen S, Ding L, et al. Current perspectives and trend of nanomedicine in cancer: A review and bibliometric analysis. J Control Release. 2022;352:211-241. doi: 10.1016/j.jconrel.2022.10.023

 

  1. Yang K, Hu Y, Qi H. Digital Health Literacy: Bibliometric Analysis. J Med Internet Res. 2022;24(7):e35816. doi: 10.2196/35816

 

  1. Falagas ME, Pitsouni EI, Malietzis GA, Pappas G. Comparison of PubMed, Scopus, Web of Science, and Google Scholar: strengths and weaknesses. FASEB J. 2007;22(2):338-342. doi: 10.1096/fj.07-9492lsf

 

  1. Selemani A, Wella K, Chen YF, Vicente-Crespo M, Uthman O, Igumbor J. A Scientometric Analysis of Africa’s Health Science Journals Indexed in International and Regional Databases: A Comparative Analysis. Int J Public Health. 2024;68. doi: 10.3389/ijph.2023.1606415

 

  1. Song C, Huang X, Chen N, Song Q, Qiu Y. A Bibliometric and Visual Analysis of Oliceridine Research (2013–2024). Drug Des Devel Ther. 2025;19:1305-1321. doi: 10.2147/dddt.s497186

 

  1. Yang Q, Zhai X, Lv Y. A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer. Front Pharmacol. 2022;13. doi: 10.3389/fphar.2022.878726

 

  1. Synnestvedt MB, Chen C, Holmes JH. CiteSpace II: visualization and knowledge discovery in bibliographic databases. AMIA Annu Symp Proc. 2005;2005:724-728.

 

  1. Wong WM, Wang X, Wang Y. The intersection of COVID- 19 and air pollution: A systematic literature network analysis and roadmap for future research. Environ Res. 2023;237:116839. doi: 10.1016/j.envres.2023.116839

 

  1. Qi F, Inagaki Y, Gao B, et al. Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas‐ and mitochondria‐mediated pathways. Cancer Sci. 2011;102(5):951-958. doi: 10.1111/j.1349-7006.2011.01900.x

 

  1. Zhu L, Chen Y, Wei C, et al. Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast cancer MCF-7 cells and its molecular mechanism. Nat Prod Res. 2017;32(4):493-497. doi: 10.1080/14786419.2017.1315575

 

  1. Bai Y, Wang X, Cai M, et al. Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition. Am J Cancer Res. 2021;11(1):200-214.

 

  1. Zhang G, Wang C, Sun M, et al. Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells. Oncotarget. 2016;7(20):28935-28946. doi: 10.18632/oncotarget.7898

 

  1. Cao Y, Yu L, Dai G, et al. Cinobufagin induces apoptosis of osteosarcoma cells through inactivation of Notch signaling. Eur J Pharmacol. 2017;794:77-84. doi: 10.1016/j.ejphar.2016.11.016

 

  1. Li X, Chen C, Dai Y, et al. Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia‐inducible factor 1α axis. Cancer Sci. 2019;110(5):1724-1734. doi: 10.1111/cas.13988

 

  1. Dai G, Zheng D, Guo W, Yang J, Cheng AY. Cinobufagin Induces Apoptosis in Osteosarcoma Cells Via the Mitochondria-Mediated Apoptotic Pathway. Cell Physiol Biochem. 2018;46(3):1134-1147. doi: 10.1159/000488842

 

  1. Meng Z, Yang P, Shen Y, et al. Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall‐cell lung cancer, or pancreatic cancer. Cancer. 2009;115(22):5309- 5318. doi: 10.1002/cncr.24602

 

  1. Pan Z, Zhang X, Yu P, et al. Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells. Front Oncol. 2019;9. doi: 10.3389/fonc.2019.00853

 

  1. Li D, Qu X, Hou K, et al. PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 2009;20(1):59-64. doi: 10.1097/cad.0b013e3283160fd6

 

  1. Yu CH, Kan SF, Pu HF, Jea Chien E, Wang PS. Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci. 2008;99(12):2467-2476. doi: 10.1111/j.1349-7006.2008.00966.x

 

  1. Sousa Barros ED, Santos Monção Filho E dos, Fonseca Pio YP, et al. Comparative study of composition of methanolic extracts of the paratoid gland secretions (PGS) of Rhinella jimi (cururu toad) from northeastern Brazil: Gender, seasonality and geographic occurrence. Toxicon. 2022;214:37-46. doi: 10.1016/j.toxicon.2022.04.020

 

  1. Yuan J, Zhou X, Cao W, et al. Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes. Nanoscale Res Lett. 2017;12(1). doi: 10.1186/s11671-017-2346-8

 

  1. Zhang D, Zhai B, Sun J, Cheng J, Zhang X, Guo D. Advances on Delivery System of Active Ingredients of Dried Toad Skin and Toad Venom. Int J Nanomedicine. 2024;19:7273-7305. doi: 10.2147/ijn.s469742

 

  1. Tang D, Feng Y, Lu J, et al. Global trends in bufalin application research for cancer from 2003 to 2022: A bibliometric and visualised analysis. Heliyon. 2024;10(2):e24395. doi: 10.1016/j.heliyon.2024.e24395

 

  1. Chen H, Li R, Zhang F, Yao Q, Guo Y. A Scientometric Visualization Analysis for Natural Products on Cancer Research from 2008 to 2020. Front Pharmacol. 2021;12. doi: 10.3389/fphar.2021.650141

 

  1. Luna Coronell JA, Syed P, Sergelen K, Gyurján I, Weinhäusel A. The current status of cancer biomarker research using tumour-associated antigens for minimal invasive and early cancer diagnostics. J Proteomics. 2012;76:102-115. doi: 10.1016/j.jprot.2012.07.022

 

  1. Sampath V, Horesh N, Sasi B, et al. Synthesis and Biological Evaluation of Novel Bufalin Derivatives. Int J Mol Sci. 2022;23(7):4007. doi: 10.3390/ijms23074007

 

  1. Fan Y, Ma Z, Zhao L, et al. Anti-tumor activities and mechanisms of Traditional Chinese medicines formulas: A review. Biomed Pharmacother. 2020;132:110820. doi: 10.1016/j.biopha.2020.110820

 

  1. Qi F, Li A, Inagaki Y, et al. Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol. 2011;11(3):342-349. doi: 10.1016/j.intimp.2010.12.007

 

  1. Tao S, Tang X, Yu L, et al. Prognosis of coronary heart disease after percutaneous coronary intervention: a bibliometric analysis over the period 2004–2022. Eur J Med Res. 2023;28(1). doi: 10.1186/s40001-023-01220-5

 

  1. ElHawary H, Barone N, Baradaran A, Janis JE. Efficacy and Safety of Migraine Surgery. Ann Surg. 2022;275(2):e315-e323. doi: 10.1097/sla.0000000000005057

 

  1. Wang X, Guo J, Gu D, Yang Y, Yang X, Zhu K. Tracking knowledge evolution, hotspots and future directions of emerging technologies in cancers research: a bibliometrics review. J Cancer. 2019;10(12):2643-2653. doi: 10.7150/jca.32739

 

  1. Asrorov AM, Kayumov M, Mukhamedov N, et al. Toad venom bufadienolides and bufotoxins: An updated review. Drug Dev Res. 2023;84(5):815-838. doi: 10.1002/ddr.22072

 

  1. Xiong X, Lu B, Tian Q, et al. Inhibition of autophagy enhances cinobufagin induced apoptosis in gastric cancer. Oncol Rep. 2018. doi: 10.3892/or.2018.6837

 

  1. Huang CJ, Zhang CY, Zhao YK, et al. Bufalin Inhibits Tumorigenesis and SREBP-1-Mediated Lipogenesis in Hepatocellular Carcinoma via Modulating the ATP1A1/ CA2 Axis. Am J Chin Med. 2023;51(2):461-485. doi: 10.1142/s0192415x23500246

 

  1. Zhang DM, Liu JS, Deng LJ, et al. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis. 2013;34(6):1331-1342. doi: 10.1093/carcin/bgt060

 

  1. Raggi C, Taddei ML, Sacco E, et al. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma. J Hepatol. 2021;74(6):1373-1385. doi: 10.1016/j.jhep.2020.12.031

 

  1. Xie C, Zhou X, Liang C, et al. Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer. J Exp Clin Cancer Res. 2021;40(1). doi: 10.1186/s13046-021-02069-4

 

  1. Rona G, Miwatani-Minter B, Zhang Q, et al. CDK-independent role of D-type cyclins in regulating DNA mismatch repair. Mol Cell. 2024;84(7):1224-1242.e13. doi: 10.1016/j.molcel.2024.02.010

 

  1. Peng L, Wen L, Shi QF, et al. Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3- mediated epithelial–mesenchymal transition and inflammation. Cell Death Dis. 2020;11(11). doi: 10.1038/s41419-020-03178-2

 

  1. Geng Z, Sun T, Yu J, et al. Cinobufagin Suppresses Lipid Peroxidation and Inflammation in Osteoporotic Mice by Promoting the Delivery of miR-3102-5p by Macrophage- Derived Exosomes. Int J Nanomedicine. 2024;19:10497- 10512. doi: 10.2147/ijn.s483849

 

  1. Sun Y, Yang H, Mei X, et al. Cinobufagin Inhibits Invasion and Migration of Non-Small Cell Lung Cancer via Regulating Glucose Metabolism Reprogramming in Tumor-Associated Macrophages. Drug Des Devel Ther. 2025;19:6647-6664. doi: 10.2147/dddt.s531190

 

  1. Dasgupta A, Emerson L. Neutralization of cardiac toxins oleandrin, oleandrigenin, bufalin, and cinobufotalin by digibind: Monitoring the effect by measuring free digitoxin concentrations. Life Sci. 1998;63(9):781-788. doi: 10.1016/s0024-3205(98)00333-6

 

  1. Li M, Wang X, Qiu Y, et al. Safety reassessment of cinobufotalin injection: new findings into cardiotoxicity. Toxicol Res. 2020;9(4):390-398. doi: 10.1093/toxres/tfaa035

 

  1. Li T, Zhang Y, Li H, et al. Bufalin CaCO3 Nanoparticles Triggered Pyroptosis through Calcium Overload via Na+/ Ca2+ Exchanger Reverse for Cancer Immunotherapy. Nano Lett. 2024;24(40):12691-12700. doi: 10.1021/acs.nanolett.4c04061

 

  1. Li Q, Liang RL, Yu QR, et al. Efficacy and safety of cinobufacini injection combined with vinorelbine and cisplatin regimen chemotherapy for stage III/IV non-small cell lung cancer. Medicine. 2020;99(31):e21539. doi: 10.1097/md.0000000000021539

 

  1. Henn D, Venter A, Botha C. In Vitro Cytotoxicity Induced by the Bufadienolides 1α,2α-Epoxyscillirosidine and Lanceotoxin B on Rat Myocardial and Mouse Neuroblastoma Cell Lines. Toxins. 2019;11(1):14. doi: 10.3390/toxins11010014

 

  1. Ba X, Wang J, Zhou S, et al. Cinobufacini protects against paclitaxel-induced peripheral neuropathic pain and suppresses TRPV1 up-regulation and spinal astrocyte activation in rats. Biomed Pharmacother. 2018;108:76-84. doi: 10.1016/j.biopha.2018.09.018

 

  1. Yau T, Galle PR, Decaens T, et al. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025;405(10492):1851-1864. doi: 10.1016/s0140-6736(25)00403-9

 

  1. Zhang J, Hong Y, Jiang L, et al. Global Metabolomic and Lipidomic Analysis Reveal the Synergistic Effect of Bufalin in Combination with Cinobufagin against HepG2 Cells. J Proteome Res. 2020;19(2):873-883. doi: 10.1021/acs.jproteome.9b00681

 

  1. Araújo R, Sorensen AA, Konkiel S, Bloem BR. Top Altmetric Scores in the Parkinson’s Disease Literature. J Parkinsons Dis. 2016;7(1):81-87. doi: 10.3233/jpd-179000
Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept