Traditional Chinese Medicine in Colorectal Cancer Therapy: A Focus on Panax quinquefolium L. through Text Mining and Network Medicine Approaches

Authors

  • Airong Ren School of Bioengineering, Zhuhai Campus of Zunyi Medical University, 519000 Zhuhai, Guangzhou, China Author
  • Mengchen Liu School of Bioengineering, Zhuhai Campus of Zunyi Medical University, 519000 Zhuhai, Guangzhou, China Author
  • Mei Huang School of Bioengineering, Zhuhai Campus of Zunyi Medical University, 519000 Zhuhai, Guangzhou, China Author
  • Shixun Zhang School of Bioengineering, Zhuhai Campus of Zunyi Medical University, 519000 Zhuhai, Guangzhou, China Author
  • Yanli Fu Department of Oncology, Shenzhen Hospital (Futian), Guangzhou University of Chinese Medicine, 518000 Shenzhen, Guangdong, China Author
  • Wei Shi School of Bioengineering, Zhuhai Campus of Zunyi Medical University, 519000 Zhuhai, Guangzhou, China Author

DOI:

https://doi.org/10.62767/jecacm502.1121

Keywords:

CRC, traditional Chinese medicine, network medicine, active ingredients

Abstract

Background: This study aimed to identify traditional Chinese medicines (TCMs) with potential anti-colorectal cancer (CRC) properties and their core active constituents. Methods: A comprehensive review of the literature regarding CRC treatment using TCM was conducted using the PubMed database. A text mining approach was employed to ascertain the correlation between TCM and CRC, highlighting the top ten TCMs. The most significantly correlated TCM underwent network medical analysis. Component data were sourced from the TCMSP and HERB databases, while their targets were identified through public databases. Concurrently, various databases were utilized to pinpoint CRC-associated target genes. Network medicine was then employed to ascertain the network proximity between component targets and CRC genes. Potential targets for both TCMs and CRC were mapped and were subsequently input into the String database to craft a protein-protein interaction (PPI) diagram. Visualization and analysis of the TCM-ingredients-targets and PPI diagrams were performed using Gephi 0.9.2. Lastly, DAVID database was used for GO and KEGG pathway enrichment analyses of the intersecting targets. Results: Text mining revealed Panax quinquefolium L. displays the most pronounced anti-CRC properties. Notably, key ingredients of Panax quinquefolium L., including Ginsenoside Rb3, Papaverine, Ginsenoside Rg3, and Ginsenoside Rb1, were found to have substantial impacts on cancer and microRNA-cancer signaling pathways. Conclusions: The TCM Panax quinquefolium L. showcases a strong potential in CRC treatment, particularly due to the efficacy of Ginsenoside Rb3 and Ginsenoside Rg3. This study provides a foundational analysis for further exploration into the therapeutic effects and underlying mechanisms of Panax quinquefolium L. in combating CRC.

References

Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians 2023; 73(1): 17-48.

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians 2021; 71(3): 209-249.

Koch T, Jørgensen JT, Christensen J, et al. Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study. International Journal of Cancer 2022; 150(1): 38-46.

Dinami R, Porru M, Amoreo CA, et al. TRF2 and VEGF-A: an unknown relationship with prognostic impact on survival of colorectal cancer patients. Journal of Experimental & Clinical Cancer Research 2020; 39(1): 111.

Li J, Ma X, Chakravarti D, et al. Genetic and biological hallmarks of colorectal cancer. Genes & Development 2021; 35(11-12): 787-820.

Qi F, Zhao L, Zhou A, et al. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. BioScience Trends 2015; 9(1): 16-34.

Yang MD, Zhou WJ, Chen XL, et al. Therapeutic Effect and Mechanism of Bushen-Jianpi-Jiedu Decoction Combined with Chemotherapeutic Drugs on Postoperative Colorectal Cancer. Frontiers in Pharmacology 2021; 12: 524663.

Zheng L, Sha J. Progress in the Application of Traditional Chinese Medicine Treatment in Postoperative Rehabilitation of Colorectal Cancer. Academic Journal of Medicine & Health Sciences 2019; 4(7): 51-57.

Li S, Wu Z, Le W. Traditional Chinese medicine for dementia. Alzheimer's & Dementia 2021; 17(6): 1066-1071.

Chen J-F, Wu S-W, Shi Z-M, et al. Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action. ChenMed 2023; 18(1): 14-45.

Zhao L, Zhang H, Li N, et al. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. Journal of Ethnopharmacology 2023; 309: 116306.

Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nature Chemical Biology 2008; 4(11): 682-690.

Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chinese Journal of Natural Medicines 2013; 11(2): 110-120.

Huang C, Zheng C, Li Y, et al. Systems pharmacology in drug discovery and therapeutic insight for herbal medicines. Briefings in Bioinformatics 2014; 15(5): 710-733.

Fang J, Wang L, Wu T, et al. Network pharmacology-based study on the mechanism of action for herbal medicines in Alzheimer treatment. Journal of Ethnopharmacology 2017; 196: 281-292.

Fang S, Dong L, Liu L, et al. HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine. Nucleic Acids Research 2021; 49(D1): D1197-D1206.

Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. Journal of Cheminformatics 2014; 16: 13.

Guney E, Menche J, Vidal M, et al. Network-based in silico drug efficacy screening. Nature Communications 2016; 7: 10331.

Ren A, Ma M, Liang Y, et al., GSZ Formula Enhances Sleep Quality: Exploring Its Active Ingredients and Mechanism Using a Network Medicine Approach. Clinical Complementary Medicine and Pharmacology 2024; 4(1): 100107.

Ren A, Wu T, Wang Y, et al. Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture. Chinese Medicine 2023; 18(1): 99.

Wang CZ, Zhang B, Song WX, et al. Steamed American ginseng berry: ginsenoside analyses and anticancer activities. Journal of Agricultural and Food Chemistry 2006; 54(26): 9936-9942.

Yang X, Zou J, Cai H, et al. Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPbeta/NF-kappaB signaling. Biomedicine & Pharmacotherapy 2017; 96: 1240-1245.

Wang CZ, Xie JT, Fishbein A, et al. Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells. Phytotherapy Research 2009; 23(1): 6-13.

Li LI, Wei L, Shen A, et al. Oleanolic acid modulates multiple intracellular targets to inhibit colorectal cancer growth. International Journal of Oncology 2015; 47(6): 2247-2254.

De Araujo Junior RF, Eich C, Jorquera C, et al. Ceramide and palmitic acid inhibit macrophage-mediated epithelial–mesenchymal transition in colorectal cancer. Molecular and Cellular Biochemistry 2020; 468(1-2): 153-168.

Phi LTH, Sari IN, Wijaya YT, et al. Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis. IUBMB Life 2019; 71(5): 601-610.

Ogata R, Mori S, Kishi S, et al. Linoleic Acid Upregulates Microrna-494 to Induce Quiescence in Colorectal Cancer. International Journal of Molecular Sciences 2021; 23(1): 225.

Jin J, Lin G, Huang H, et al. Capsaicin Mediates Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells via Stabilizing and Activating p53. International Journal of Biological Sciences 2014; 10(3): 285-295.

Sarhene M, Ni JY, Duncan ES, et al. Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action. Pharmacological Research 2021, 166: 105481.

Wang M, Chen X, Jin W, et al. Ginsenoside Rb3 exerts protective properties against cigarette smoke extract-induced cell injury by inhibiting the p38 MAPK/NF-kappaB and TGF-beta1/VEGF pathways in fibroblasts and epithelial cells. Biomedicine & Pharmacotherapy 2018; 108: 1751-1758.

Huang G, Khan I, Li X, et al. Ginsenosides Rb3 and Rd reduce polyps formation while reinstate the dysbioticgut microbiota and the intestinal microenvironment in ApcMin/+ mice. Scientific Reports 2017; 7(1): 12552.

Nohl H, Rohr-Udilova N, Gille L, et al. Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat. Biofactors 2005; 25(1-4): 87-95.

Jiang L, Yin X, Chen YH, et al. Proteomic analysis reveals ginsenoside Rb1 attenuates myocardial ischemia/reperfusion injury through inhibiting ROS production from mitochondrial complex I. Theranostics 2021; 11(4): 1703-1720.

Jardim KV, Siqueira JLN, Báo SN, et al. The role of the lecithin addition in the properties and cytotoxic activity of chitosan and chondroitin sulfate nanoparticles containing curcumin. Carbohydrate Polymers 2020; 227: 115351.

Bot F, Cossuta D, O'Mahony JA. Inter-relationships between composition, physicochemical properties and functionality of lecithin ingredients. Trends in Food Science & Technology 2021; 111: 261-270.

Rego RL, Foster NR, Smyrk TC, et al. Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status. British Journal of Cancer 2010; 102(1): 165-172.

Nwaokorie A, Fey D. Personalised Medicine for Colorectal Cancer Using Mechanism-Based Machine Learning Models. International Journal of Molecular Sciences 2021; 22(18): 9970.

Morteau O, Morham SG, Sellon R, et al. Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2. The Journal of Clinical Investigation 2000; 105(4): 469-478.

Zahedi T, Colagar AH, Mahmoodzadeh H. PTGS2 Over-Expression: A Colorectal Carcinoma Initiator not an Invasive Factor. Reports of Biochemistry & Molecular Biology 2021; 9(4): 442-451.

Ashrafizadeh M, Zarrabi A, Hushmandi K, et al. MicroRNAs in cancer therapy: Their involvement in oxaliplatin sensitivity/resistance of cancer cells with a focus on colorectal cancer. Life Sciences 2020; 256: 117973.

Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009; 58(10): 1375-1381.

Li H, Liang J, Wang J, et al. Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p. Cancer Communications 2021; 41(6): 472-491.

Luck K, Kim DK, Lambourne L, et al. A reference map of the human binary protein interactome. Nature 2020; 580(7803): 402-408.

Graves-Deal R, Bogatcheva G, Rehman S, et al. Broad-spectrum receptor tyrosine kinase inhibitors overcome de novo and acquired modes of resistance to EGFR-targeted therapies in colorectal cancer. Oncotarget 2019; 10(13): 1320-1333.

Zhou J, Ji Q, Li Q. Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies. Journal of Experimental & Clinical Cancer Research 2021; 40(1): 328.

Additional Files

Published

2024-05-17

Data Availability Statement

The analyzed data sets generated during the study are available from the corresponding author upon reasonable request.

Issue

Section

Original Research

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