Antioxidant, Antibacterial and Anticancer Properties of Viscum Album ssp. Austriacum Methanol Extract

Abstract

Mistletoe species is widely used in traditional medicine to treat diseases such as cancer, cataracts, and rheumatoid arthritis. The present study was deigned to intestigate the antibacterial, antioxidant, and anticancer effects of mistletoe. The findings of the study revealed that the ability of mistletoe to scavenge DPPH radicals was found to be 69 % at a dose of 400 μg ml-1. Antimicrobial activity tests showed inhibitory effects on bacteria by inhibiting colony formation in bacterial species at doses ranging from 8 mg ml-1 to 0,5 mg ml-1. In the cell viability test, the extract effectively reduced cell viability, with an IC50 value of 3.2 mg ml-1 for the SK-MEL-30 cell line and an IC50 of 3.15 mg ml-1 for the A2058 cell line. In conclusion, the methanol extract has potential as a new therapeutic agent in terms of antioxidant, antibacterial and anticancer activity.

Keywords

• Viscum album spp. austriacum
• antioxidant
• antibacterial
• anticancer

References

1. Atta E., Mohamed N., and Abdelgawad A. (2017). Antioxidants: an overview on the natural and synthetic types, European Chemical Bulletin. 6,8,365375.https://doi.org/10.17628/ecb.2017.6.374-384
2. Balunas, M. J., & Kinghorn, A. D. (2005). Drug discovery from medicinal plants. Life Sciences,78(5),431-441. https://doi.org/10.1016/j.lfs.2005.09.012
3. Başar, Y., Yenigün, S., Behçet, L., … Ozen, T. (2024). Antibacterial and Antioxidant Molecule Isolated from Nepeta aristata Boiss Et Kotschy Ex Boiss plant: 1,5,9-Epideoxyloganic Acid. International Journal of Chemistry and Technology, 8(1), 27-31. https://doi.org/10.32571/ijct.1381998
4. Bostanci, M. T., Bulbul, A. S., Celik, I. S., Kocabas, Y. Z. Burhan, H., Bayat, R., & Karimi-Maleh, H. (2022). Investigation of antibacterial, antifungal, antibiofilm, antioxidant and anticancer properties of methanol extracts of Salvia marashica İlçim, Celep & Doğan and Salvia caespitosa Montbret & Aucher ex Benth plants withmedicinalimportance. Chemosphere, 288(2). https://doi.org/10.1016/j.chemosphere.2021.132602
5. Böhling, N., Greuter W., Raus T., Snogerup, B., Snogerup, S., Zuber, D. (2002). Notes on the cretan mistletoe, Viscum album subsp. creticum subsp. nova (Loranthaceae/Viscaceae). Journal of Plant Sciences, 50(sup1) 77-84.
6. Cardile, V., Russo, A., Formisano, C., Rigano, D., Senatore, F., Arnold, N. A., & Piozzi, F. (2009). Essential oils of Salvia bracteata and Salvia rubifolia from Lebanon: Chemical composition, antimicrobial activity and inhibitory effect on human melano macells. Journal of Ethnopharmacology, 126(2), 265-272. https://doi.org/10.1016/j.jep.2009.08.026
7. Cardil Kaur, C., Kapoor, H.C. (2001). Antioxidants in fruits and vegetables–the Millennium’s health. International Journal of Food Science and Technology,36(7),703-725. https://doi.org/10.1111/j.13652621.2001.00513.x
8. Çelik, İ. S., Aygan, A., Çiçek, M., & Kocabaş, Y. Z. (2023). Cytotoxic effect of prunus divaricata ledeb. extract on lung cancer cells and determination of expression profiles of genes in the MAP-Kinase pathway. Sakarya University Journal of Science, 27(1), 181-188. https://doi.org/10.16984/saufenbilder.1221057

9. Evyapan, G., Senturk, N. C., & Celik, I. S. (2024). Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-small Cell Lung Cancer (NSCLC) via Downregulation of VEGFA/VEGFR2/NRP-1and PI3K/AKT/mTORPathways. Cell biochemistry and biophysics, 82(4), 3277-3285. https://doi.org/10.1007/s12013-024-01501-8
10. Galun, D., Tröger, W., Reif, M. 2015. Mistletoe extract therapy no antineoplastic therapy: a randomized clinical trial on overall survival and quality of life in pancreatic cancer patients. Phytomedicine.22(1),S6. https://doi.org/10.1016/j.phymed.2015.05.028
11. Garcıa-Alonso, M., De Pascual-Teresa, S., Santos-Buegla, C., & Rivas-Gonzalo, J. C. (2004). Evaluation of the antioxidant properties of fruits. FoodChemistry,84(1)13-18. https://doi.org/10.1016/S0308-8146(03)00160-2
12. García-García, J. D., Anguiano-Cabello, J. C., Arredondo-Valdés, R., Candido del Toro, C. A., Martínez-Hernández, J. L., Segura-Ceniceros, E. P., & Ilyina, A. (2021). Phytochemical characterization of Phoradendron bollanum and V. album subs. austriacum as Mexican mistletoe plants with antimicrobial activity. Plants, 10(7), 1299. https://doi.org/10.3390/plants10071299
13. Glatzel, G., Geils, W.B. (2009). Mistletoe ecophysiology: Host-parasite interactions. Botany 87(1), 10-15. https://doi.org/10.1139/B08-096
14. Hanahan, D., Weinberg, R.A. (2000) The hallmarks ofcancer.Cell,100(1),57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
15. Kähkönen, M., Hopia, A., Vuorela, H., Rauha, J., Pihlaja, K., Kujala, T., & Heinonen, M. (1999). Antioxidant activity of plant extracts containing phenolic compounds. Journal of agricultural and foodchemistry,47(10),3954-3962. https://doi.org/10.1021/jf990146l
16. Kamatou, G. P. P., Van Zyl, R. L., Davids, H., Van Heerden, F. R., Lourens, A. C. U., & Viljoen, A. M. (2008). Antimalarial and anticancer activities of selected South African Salvia species and isolated compounds from S. radula. South African Journal of Botany,74(2),238–243. https://doi.org/10.1016/j.sajb.2007.11.002
17. Martemucci, G., Costagliola, C., Mariano, M., D’andrea, L., Napolitano, P., & D’Alessandro, A. G. (2022). Free radical properties, source and targets, antioxidant consumption and health. Oxygen, 2(2), 48-78. https://doi.org/10.3390/oxygen2020006
18. Marvibaigi, M., Supriyanto, E., Amini, N. Abdul Majid, F. A., & Jaganathan, S. K. (2014). Preclinical and clinical effects of mistletoe against breast cancer. BioMed research international, 2014(1), http://dx.doi.org/10.1155/2014/785479
19. Matias, E. F. F., Alves, E. F., Santos, B. S., Sobral de Souza, C. E., Alencar Ferreira, J. V. D., Santos de Lavor, A. K. L., ... & da Costa, J. G. M. (2013). Biological activities and chemical characterization of Cordia verbenacea DC. as tool to validate the ethnobiologicalusage. Evidence‐Based Complementary and Alternative Medicine, 2013(1), 164215. https://doi.org/10.1155/2013/164215
20. Mennan, H., Pala, F., ve Üstüner, T. (2021). Yabancı ot biliminde güncel konular. İksad yayınları, Online kitap, Sayfa, 1-770
21. Miller, A.G. (1982). Loranthaceae. In: Davis PH (ed.). Flora of Turkey and the East Aegean Islands,” Edinburg University Press 7. 547
22. Mushtaq, W., Ishtiaq, M., Maqbool, M., Mazhar, M. W., Casini, R., Abd-ElGawad, A. M., & Elansary, H. O. (2023). Green synthesis of zinc oxide nanoparticles using V. album extracts: Unveiling bioactive compounds, antibacterial potential, and antioxidant activities. Plants, 12(11), 2130. https://doi.org/10.3390/plants12112130
23. Orhan, D. D., Aslan, M., Sendogdu, N., Ergun, F., & Yesilada, E. (2005). Evaluation of the hypoglycemic effect and antioxidant activity of three V. album subspecies (European mistletoe) in streptozotocin-diabetic rats. Journal of ethnopharmacology,98(1-2),95-102. https://doi.org/10.1016/j.jep.2004.12.033
24. Ohikhena, F. U., Wintola, O. A., & Afolayan, A. J. (2017). Evaluation of the antibacterial andantifungal properties of Phragmanthera capitata (Sprengel) Balle (Loranthaceae), a mistletoe growing on rubber tree, using the dilution techniques. The Scientific WorldJournal,2017(1), https://doi.org/10.1155/2017/9658598
25. ÖnayUçar, E., Karagöz, A., & Arda, N. (2006). Antioxidant activity of V. album ssp. album. Fitoterapia,77(7-8),556-560. https://doi.org/10.1016/j.fitote.2006.08.001
26. Pietrzak, W., & Nowak, R. (2021). Impact of harvest conditions and host tree species on chemical composition and antioxidant activity of extracts from V. album L. Molecules, 26(12), 3741. https://doi.org/10.3390/molecules26123741
27. Popp, M., & Richter, A. (1998). Ecophysiology of xylemtapping mistletoes. H.D. Behnke, K. Esser, J. W. Kadereit, U. Lüttge, and M. Runge. Progress in Botany (59, Pp 659–674). Springer-Verlag Berlin Heidelberg 1998
28. Radenkovic, M., Ivetic, V., Popovic, M., Brankovic, S., & Gvozdenovic, L. (2009). Effects of mistletoe (V. album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. Clinical and experimental Hypertension, 31(1), 11-19. https://doi.org/10.1080/10641960802409820
29. Sallé, G. (1983). Germination and Establishment of V. album L. In The Biology of Mistletoes; Academic Press Sydney Australia, 154-159
30. Schulze, E.D., Turner, N.C., Glatzel, C.G. (1984). Water and nutrient relations of two mistletoes and their hosts: An hypothesis. Plant Cell Environ. 7(5), 293-299. https://doi.org/10.1111/13653040.ep11589756
31. Shan, B., Cai, Y. Z., Brooks, J. D., & Corke, H. (2007). The in vitro antibacterial activity of dietary spice and medicinal herb extracts. International Journal of Food Microbiology, 117(1-2), 112-119.https://doi.org/10.1016/j.ijfoodmicro.2007.03.003
32. Szurpnicka, A., Kowalczuk, A., & Szterk, A. (2020). Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action. Archives of Pharmacal Research, 43(6), 593-629. https://doi.org/10.1007/s12272-020-01247-w Şahin, B., Bülbül, A. S., Çelik, İ. S., Korkmaz, N., & Karadağ, A. (2022). Investigation of biological activities of plant extract and green synthesis silvernanoparticles obtained from Gilaburu (Viburnum opulus L.) fruits. Turkish Journal of Chemistry,46(1),224-235. https://doi.org/10.3906/kim-2108-48
33. Tabiasco, J., Pont, F., Fournié, J. J., & Vercellone, A. (2002). Mistletoe viscotoxins increase natural killer cell‐mediated cytotoxicity. European Journal of Biochemistry, 269(10), 2591-2600. https://doi.org/10.1046/j.14321033.2002.02932.x
34. Tekel, Y. K., Alma, M. H., Başar, Y., Nas, M. S., Atalar, M. N., Karadağ, M., Abdelsalam, A.H., & Arslan, Ş. (2025). Phytochemical analysis, molecular docking, in vitro cytotoxicity, enzyme inhibition and antioxidant activity of V. album subsp. austriacum in Turkey. Biocatalysis and Agricultural Biotechnology, 67, 103646. https://doi.org/10.1016/j.bcab.2025.103646
35. Tuorkey, M. J. (2015). Cancer therapy with phytochemicals: Present and future perspectives. Biomedical and Environmental Sciences, 28(11), 808–819. https://doi.org/10.3967/bes2015.114
36. Twardziok, M., Kleinsimon, S., Rolff, J., Jäger, S., Eggert, A., Seifert, G., & Delebinski, C. I. (2016). Multiple active compounds from V. album L. synergistically converge to promote apoptosis in Ewing sarcoma. PLoS One, 11(9), https://doi.org/10.1371/journal.pone.0159749
37. Üstüner, T. (2003). Identification and density of Viscum species in Nigde province. Türkiye Herboloji Dergisi, 6( 2), 45-53
38. Üstüner, T. (2018). Investigation of symptoms and hosts of semi parasite plant species in east mediterranean and central anatolia region of Turkey. KSÜ Tarım ve Doğa Dergisi 21 (3), 438-446. https://doi.org/10.18016/ksudobil.350489
39. Vicaş, S. I., Rugina, O. D., Leopold, L., PInTEA, A., & Socaciu, C. (2011). HPLC fingerprint of bioactive compounds and antioxidant activities of Viscum album from different host trees. Notulae Botanicae Horti Agrobotanici Cluj-Napoca,39(1),48-57. https://doi.org/10.15835/nbha3913455
40. Xie, W., Adolf, J., & Melzig, M. F. (2017). Identification of V. album L. miRNAs and prediction of their medicinal values. PLoS One, 12(11).https://doi.org/10.1371/journal.pone.0187776
41. Weis, J., Bartsch, H. H., Hennies, F., Rietschel, M., Heim, M., Adam, G., U. Gärtner, U., & Ammon, A. (1998). Complementary medicine in cancer patients: demand, patient’attitudes and psychological beliefs. Oncology Research andTreatment, 21(2),144-149. https://doi.org/10.1159/000026796
42. Zuber, D. (2004). Biological flora of Central Europe V. album L., Flora-Morphol. Distrib. Funct. Ecology Plants, 199(3), 181-203. https://doi.org/10.1078/0367-2530-00147