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Abstract
Background: The COVID-19 pandemic, which has unfolded over the past years, poses significant threats to global public health and socioeconomic well-being. Three herbs (radix Angelica dahurica, Chuanxiong rhizoma, and Cyperi rhizoma) have been long utilized in combination for treating common colds and flu.
Objective: To analyze potential biotargets and explore possible effects of plant-derived compounds from 3 herbs towards COVID-19 treatment.
Method: Bioinformatics databases and network pharmacology were employed to identify bioactive compounds and their biotargets with integrated statistical calculation, followed by Gene Ontology enrichment. KEGG pathway analysis was performed to elucidate the involvement of selected bioactive compounds in COVID-19-related processes.
Results: Network pharmacology highlighted essential receptors, cytokines, and signaling proteins. Gene Ontology analysis revealed associations with signal transduction, RNA transcription enzymes, and crucial cellular components. Molecular function analysis emphasized interactions related to virus entry. KEGG analysis uncovered 32 potential targets across various pathways, elucidating their role in inflammation and cytokine storms.
Conclusion: This study provides new insight for the molecular mechanisms underlying the therapeutic potential of a combination of radix Angelica dahurica, Chuanxiong rhizoma, and Cyperi rhizoma against COVID-19. The identified targets and pathways offer new directions for further experimental validation, paving the way for potential therapeutic interventions for COVID-19.
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References
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- Palacios, Y., Ruiz, A., Ramon-Luing, L. A., Ocana-Guzman, R., Barreto-Rodriguez, O., Sanchez-Moncivais, A., Tecuatzi-Cadena, B., Regalado-Garcia, A. G., Pineda-Gudino, R. D., Garcia-Martinez, A., Juarez-Hernandez, F., Farias-Contreras, J. P., Fricke-Galindo, I., Perez-Rubio, G., Falfan-Valencia, R., Buendia-Roldan, I., Medina-Quero, K. & Chavez-Galan, L. (2021). Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality. International Journal of Molecular Sciences, 22(16), 1-17. https://doi.org/10.3390/ijms22168423.
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References
Asif, M., Saleem, M., Saadullah, M., Yaseen, H. S. & Al Zarzour, R. (2020). COVID-19 and Therapy With
Essential Oils Having Antiviral, Anti-Inflammatory, and Immunomodulatory Properties. Inflammopharmacology, 28(5), 1153-1161. https://doi.org/10.1007/s10787-020-00744-0.
Choudhary, S., Sharma, K. & Silakari, O. (2021). The Interplay Between Inflammatory Pathways and
COVID-19: A Critical Review On Pathogenesis and Therapeutic Options. Microbial Pathogenesis, 150, 1-21. https://doi.org/10.1016/j.micpath.2020.104673.
Daina, A., Michielin, O. & Zoete, V. (2017). SwissADME: A Free Web Tool To Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Scientific Reports, 7, 1-13. https://doi.org/10.1038/srep42717.
Ding, X., Fan, L. L., Zhang, S. X., Ma, X. X., Meng, P. F., Li, L. P., Huang, M. Y., Guo, J. L., Zhong, P. Z. & Xu,
L. R. (2022). Traditional Chinese Medicine in Treatment of COVID-19 and Viral Disease: Efficacies and Clinical Evidence. International Journal of General Medicine, 15, 8353-8363. https://doi.org/10.2147/IJGM.S386375.
Donkor, P. O., Chen, Y., Ding, L. & Qiu, F. (2016). Locally and Traditionally Used Ligusticum Species–A
Review of Their Phytochemistry, Pharmacology and Pharmacokinetics. Journal of Ethnopharmacology, 194, 530-548. https://doi.org/10.1016/j.jep.2016.10.012.
Fan, A. Y., Gu, S., Alemi, S. F. & Research Group For Evidence-Based Chinese, M. (2020). Chinese Herbal Medicine For COVID-19: Current Evidence With Systematic Review and Meta-Analysis. Journal of Integrative Medicine, 18(5), 385-394. https://doi.org/ 10.1016/j.joim.2020.07.008.
Filip, R., Gheorghita Puscaselu, R., Anchidin-Norocel, L., Dimian, M. & Savage, W. K. (2022). Global Challenges to Public Health Care Systems during the COVID-19 Pandemic: A Review of Pandemic Measures and Problems. Journal of Personalized Medicine, 12(8), 1-22. https://doi.org/10.3390/jpm12081295.
Gfeller, D., Grosdidier, A., Wirth, M., Daina, A., Michielin, O. & Zoete, V. (2014). SwissTargetPrediction: A Web Server For Target Prediction of Bioactive Small Molecules. Nucleic Acids Research, 42, 32-38. https://doi.org/10.1093/nar/gku293.
Gupta, N., Ish, P. & Agstam, S. (2020). Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blocker In Coronavirus Disease 2019: Safe and Possibly Beneficial. Lung India, 37(4), 352-353. https://doi.org/ 10.4103/lungindia.lungindia_237_20.
Huang, C.-W., Ha, H.-A., Tsai, S.-C., Lu, C.-C., Lee, C.-Y., Tsai, Y.-F., Tsai, F.-J., Chiu, Y.-J., Wang, G.-K., Hsu, C.-H. & Yang, J.-S. (2021). In Silico Target Analysis of Treatment for COVID-19 Using Huang-Lian-Shang-Qing-Wan, a Traditional Chinese Medicine Formula. Natural Product Communications, 16(10), 1-18. https://doi.org/10.1177/1934578X211030818
Jiang, S., Hillyer, C. & Du, L. (2020). Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends in Immunology, 41(5), 355-359. https://doi.org/ 10.1016/j.it.2020.03.007.
Kamala, A., Middha, S. K. & Karigar, C. S. (2018). Plants In Traditional Medicine With Special Reference To Cyperus rotundus L.: A Review. 3 Biotech, 8(7), 1-11. https://doi.org/10.1007/s13205-018-1328-6.
Kanehisa, M. & Goto, S. 2000. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research, 28(1), 27-30. https://doi.org/ 10.1093/nar/28.1.27.
Kang, Z., Wu, Q., Peng, Q., Deng, Y., Xu, H., Xiao, Y., Li, J., Li, S., Li, J. & Chen, Y. (2024). Deciphering The Potential Therapeutic Targets and Mechanisms of Jaranol For The Treatment of COVID-19 and Lung Adenocarcinoma. Arabian Journal of Chemistry, 17(3), 1-11. https://doi.org/10.1016/j.arabjc.2024.105648.
Lee, B. W., Ha, T. K. Q., Cho, H. M., An, J.-P., Kim, S. K., Kim, C.-S., Kim, E. & Oh, W. K. (2020). Antiviral Activity of Furanocoumarins Isolated From Angelica dahurica Against Influenza A Viruses H1N1 and H9N2. Journal of Ethnopharmacology, 15(259), 1-11. https://doi.org/10.1016/j.jep.2020.112945
Liu, Z. (2010). Essentials of Chinese Medicine, Springer Science & Business Media.
Loganathan, V., Akbar, I., Ahamed, A., Alodaini, H. A., Hatamleh, A. A., Abuthkir, M. H. S. & Gurusamy, R. (2024). Synthesis, Antimicrobial and Cytotoxic Activities of Tetrazole N-Mannich Base Derivatives: Investigation of DFT Calculation, Molecular Docking, and Swiss ADME Studies. Journal of Molecular Structure, 1300. https://doi.org/10.1016/j.molstruc.2023.137239.
Mikulicic, S., Finke, J., Boukhallouk, F., Wustenhagen, E., Sons, D., Homsi, Y., Reiss, K., Lang, T. & Florin, L. (2019). ADAM17-dependent Signaling Is Required For Oncogenic Human Papillomavirus Entry Platform Assembly. Elife, 8, 1-29. https://doi.org/10.7554/eLife.44345.
Palacios, Y., Ruiz, A., Ramon-Luing, L. A., Ocana-Guzman, R., Barreto-Rodriguez, O., Sanchez-Moncivais, A., Tecuatzi-Cadena, B., Regalado-Garcia, A. G., Pineda-Gudino, R. D., Garcia-Martinez, A., Juarez-Hernandez, F., Farias-Contreras, J. P., Fricke-Galindo, I., Perez-Rubio, G., Falfan-Valencia, R., Buendia-Roldan, I., Medina-Quero, K. & Chavez-Galan, L. (2021). Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality. International Journal of Molecular Sciences, 22(16), 1-17. https://doi.org/10.3390/ijms22168423.
Pinero, J., Bravo, A., Queralt-Rosinach, N., Gutierrez-Sacristan, A., Deu-Pons, J., Centeno, E., Garcia-Garcia, J., Sanz, F. & Furlong, L. I. (2017). DisGeNET: A Comprehensive Platform Integrating Information On Human Disease-Associated Genes and Variants. Nucleic Acids Research, 45(1), 833-839. https://doi.org/10.1093/nar/gkw943.
Ru, J., Li, P., Wang, J., Zhou, W., Li, B., Huang, C., Li, P., Guo, Z., Tao, W., Yang, Y., Xu, X., Li, Y., Wang, Y. & Yang, L. (2014). TCMSP: A Database of Systems Pharmacology For Drug Discovery From Herbal Medicines. Journal of Cheminformatics, 6(13), 1-6. https://doi.org/10.1186/1758-2946-6-13.
Safa, O., Hassaniazad, M., Farashahinejad, M., Davoodian, P., Dadvand, H., Hassanipour, S. & Fathalipour, M. (2020). Effects of Ginger on Clinical Manifestations and Paraclinical Features of Patients With Severe Acute Respiratory Syndrome due to COVID-19: A Structured Summary of A Study Protocol For A Randomized Controlled Trial. Trials, 21(1), 1-2. https://doi.org/10.1186/s13063-020-04765-6.
Sherman, B. T., Hao, M., Qiu, J., Jiao, X., Baseler, M. W., Lane, H. C., Imamichi, T. & Chang, W. (2022). DAVID: A Web Server For Functional Enrichment Analysis And Functional Annotation of Gene Lists (2021 update). Nucleic Acids Research, 50(1), 216-221. https://doi.org/10.1093/nar/gkac194.
Solnier, J. & Fladerer, J.-P. (2020). Flavonoids: A Complementary Approach To Conventional Therapy of COVID-19? Phytochemistry Reviews, 20(4), 773-795. https://doi.org/10.1007/s11101-020-09720-6.
Szklarczyk, D., Gable, A. L., Nastou, K. C., Lyon, D., Kirsch, R., Pyysalo, S., Doncheva, N. T., Legeay, M., Fang, T., Bork, P., Jensen, L. J. & Von Mering, C. (2021). The STRING Database in 2021: Customizable Protein-Protein Networks, and Functional Characterization of User-Uploaded Gene/Measurement Sets. Nucleic Acids Research, 49(1), 605-612. https://doi.org/10.1093/nar/gkaa1074.
V'kovski, P., Kratzel, A., Steiner, S., Stalder, H. & Thiel, V. (2021). Coronavirus Biology and Replication: Implications For SARS-CoV-2. Nature Reviews Microbiology, 19(3), 155-170. https://doi.org/ 10.1038/s41579-020-00468-6.
Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D. & Zhou, Y. (2021). The Signal Pathways and Treatment of Cytokine Storm in COVID-19.
Signal Transduction and Targeted Therapy, 6(1), 1-20. https://doi.org/10.1038/s41392-021-00679-0.
Zhang, C., Fan, L., Fan, S., Wang, J., Luo, T., Tang, Y., Chen, Z. & Yu, L. 2019. Cinnamomum cassia Presl: A Review of Its Traditional Uses, Phytochemistry, Pharmacology and Toxicology. Molecules, 24(19), 1-31. https://doi.org/ 10.3390/molecules24193473.