| Viscum album contains three lectins, differing in their specificity for glycoprotein sites on cell membranes. These are mistletoe lectin 1, 2, and 3 or ML-1, Ml-2, and ML-3. Mistletoe lectin 1 has had the most amount of research. Mistletoe lectins, as members of the type 2 RIP family, are composed of two protein portions linked by a disulfide bond. The A chain is a strong inhibitor of the ribosome, the cellular protein manufacturing organelle. The B chain has strong and selective binding affinity to carbohydrate molecules on the cell surface.<ref>{{cite journal | vauthors=((Hajtó, T.)), ((Hostanska, K.)), ((Berki, T.)), ((Pálinkás, L.)), ((Boldizsár, F.)), ((Németh, P.)) | journal=Evidence-Based Complementary and Alternative Medicine | title=Oncopharmacological perspectives of a plant lectin (Viscum album agglutinin-I): overview of recent results from in vitro experiments and in vivo animal models, and their possible relevance for clinical applications | volume=2 | issue=1 | pages=59–67 | date= 2005}}</ref> | | Viscum album contains three lectins, differing in their specificity for glycoprotein sites on cell membranes. These are mistletoe lectin 1, 2, and 3 or ML-1, Ml-2, and ML-3. Mistletoe lectin 1 has had the most amount of research. Mistletoe lectins, as members of the type 2 RIP family, are composed of two protein portions linked by a disulfide bond. The A chain is a strong inhibitor of the ribosome, the cellular protein manufacturing organelle. The B chain has strong and selective binding affinity to carbohydrate molecules on the cell surface.<ref>{{cite journal | vauthors=((Hajtó, T.)), ((Hostanska, K.)), ((Berki, T.)), ((Pálinkás, L.)), ((Boldizsár, F.)), ((Németh, P.)) | journal=Evidence-Based Complementary and Alternative Medicine | title=Oncopharmacological perspectives of a plant lectin (Viscum album agglutinin-I): overview of recent results from in vitro experiments and in vivo animal models, and their possible relevance for clinical applications | volume=2 | issue=1 | pages=59–67 | date= 2005}}</ref> |
− | [[File:Viscotoxins.jpg|alt=Molecular model of viscotoxins opening a pore in the tumor cell membrane|left|thumb|The model that describes the action of viscotoxins against tumor cells. "Frequently cited models for activity of antimicrobial peptides. '''a''' AMPs diffusing through solution, '''b''' AMPs adsorption to the membrane. After the threshold concentration is achieved, peptide molecules begin to reorient in the lipid bilayer '''(c)'''. Their further fate may be described using one of three models. The first, depicted in the '''d''' is called barrel-stave model. In this scenario, hydrophobic regions of AMPs align with the tails of the lipids and the hydrophilic residues form the inner surface of the forming pore. According to the wormhole model (called also toroidal pore model, shown in '''e)''' during peptides aggregation, hydrophilic heads of the lipids are electrostatically dragged by charged residues of AMPs. The membrane bends, two layers merge and form continuous surface surrounding the pore. The carpet model shown in '''f''' assumes, that at large concentrations, peptide molecules disrupt the membrane in a detergent-like manner breaking the lipid bilayer into set of separate micelles" from Nawrot, R., Barylski, J., Nowicki, G., Broniarczyk, J., Buchwald, W., & Goździcka-Józefiak, A. (2014). Plant antimicrobial peptides. Folia microbiologica, 59(3), 181–196. <nowiki>https://doi.org/10.1007/s12223-013-0280-4</nowiki>]] | + | |
| + | In tumor cells mistletoe lectins cause apoptosis by inhibiting the ribosomal subunit. In the human body several immune enhancing effects are noteworthy. Leukocytes and granulocytes are upregulated, and it appears that mistletoe lectins are responsible for the increase in eosinophils seen with mistletoe use.<ref>{{cite journal | vauthors=((R, H.)), ((M, R.)), ((R, G.)), ((R, L.)), ((K, U.)), ((R, K.)) | journal=Journal of the Society for Integrative Oncology | title=Immunologic effects of mistletoe lectins: a placebo-controlled study in healthy subjects | volume=4 | issue=1 | date= Winter 2006 | url=https://pubmed.ncbi.nlm.nih.gov/16737665/ | access-date=2 April 2023}}</ref> Lectins cause the release of the interleukins IL-1 and tumor necrosis factor-α. Dendritic cells, natural killer cells, cytotoxic T cells, and macrophages are upregulated, while T helper cells are modulated in a manner favorable to tumor cell elimination.<ref>{{cite journal | vauthors=((Elluru, S.)), ((Duong Van Huyen, J.-P.)), ((Delignat, S.)), ((Prost, F.)), ((Bayry, J.)), ((Kazatchkine, M. D.)), ((Kaveri, S. V.)) | journal=Arzneimittel-Forschung | title=Molecular mechanisms underlying the immunomodulatory effects of mistletoe (Viscum album L.) extracts Iscador | volume=56 | issue=6A | pages=461–466 | date= June 2006 | doi=10.1055/s-0031-1296813}}</ref>[[File:Viscotoxins.jpg|alt=Molecular model of viscotoxins opening a pore in the tumor cell membrane|left|thumb|The model that describes the action of viscotoxins against tumor cells. "Frequently cited models for activity of antimicrobial peptides. '''a''' AMPs diffusing through solution, '''b''' AMPs adsorption to the membrane. After the threshold concentration is achieved, peptide molecules begin to reorient in the lipid bilayer '''(c)'''. Their further fate may be described using one of three models. The first, depicted in the '''d''' is called barrel-stave model. In this scenario, hydrophobic regions of AMPs align with the tails of the lipids and the hydrophilic residues form the inner surface of the forming pore. According to the wormhole model (called also toroidal pore model, shown in '''e)''' during peptides aggregation, hydrophilic heads of the lipids are electrostatically dragged by charged residues of AMPs. The membrane bends, two layers merge and form continuous surface surrounding the pore. The carpet model shown in '''f''' assumes, that at large concentrations, peptide molecules disrupt the membrane in a detergent-like manner breaking the lipid bilayer into set of separate micelles" from Nawrot, R., Barylski, J., Nowicki, G., Broniarczyk, J., Buchwald, W., & Goździcka-Józefiak, A. (2014). Plant antimicrobial peptides. Folia microbiologica, 59(3), 181–196. <nowiki>https://doi.org/10.1007/s12223-013-0280-4</nowiki>]] |
| Viscotoxins are a 46 amino acid long group of compounds with a net positive charge and 3 disulfide bonds. There are 7 isoforms of viscotoxins from viscum album A1, A2, A3, B, B2, 1-PS and C1, with U-PS being an eighth more distantly related compound. Viscotoxins are hypothesized to interact with phosphatidylserine that is a prominent feature of cancer cells membranes, opening a hole in the cell membrane and destabilizing the DNA.<ref>{{cite journal | vauthors=((Samuelsson, G.)), ((Pettersson, B. M.)) | journal=European Journal of Biochemistry | title=The Amino Acid Sequence of Viscotoxin B from the European Mistletoe (Viscum album L, Loranthaceae) | volume=21 | issue=1 | pages=86–89 | date= 1971 | url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1432-1033.1971.tb01443.x | doi=10.1111/j.1432-1033.1971.tb01443.x | access-date=27 March 2023}}</ref><ref>{{cite journal | vauthors=((Pal, A.)), ((Debreczeni, J. É.)), ((Sevvana, M.)), ((Gruene, T.)), ((Kahle, B.)), ((Zeeck, A.)), ((Sheldrick, G. M.)) | journal=Acta Crystallographica Section D Biological Crystallography | title=Structures of viscotoxins A1 and B2 from European mistletoe solved using native data alone | volume=64 | issue=9 | pages=985–992 | date=1 September 2008 | url=https://scripts.iucr.org/cgi-bin/paper?S0907444908022646 | doi=10.1107/S0907444908022646 | access-date=27 March 2023}}</ref><ref>{{cite journal | vauthors=((Nawrot, R.)), ((Barylski, J.)), ((Nowicki, G.)), ((Broniarczyk, J.)), ((Buchwald, W.)), ((Goździcka-Józefiak, A.)) | journal=Folia Microbiologica | title=Plant antimicrobial peptides | volume=59 | issue=3 | pages=181–196 | date= 2014 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971460/ | doi=10.1007/s12223-013-0280-4 | access-date=27 March 2023}}</ref> Viscotoxins have been shown to act as an antimicrobial compound, specifically having anti-fungal activity.<ref>{{cite journal | vauthors=((Giudici, A. M.)), ((Regente, M. C.)), ((Villalaín, J.)), ((Pfüller, K.)), ((Pfüller, U.)), ((De La Canal, L.)) | journal=Physiologia Plantarum | title=Mistletoe viscotoxins induce membrane permeabilization and spore death in phytopathogenic fungi | volume=121 | issue=1 | pages=2–7 | date= 2004 | url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0031-9317.2004.00259.x | doi=10.1111/j.0031-9317.2004.00259.x | access-date=27 March 2023}}</ref> | | Viscotoxins are a 46 amino acid long group of compounds with a net positive charge and 3 disulfide bonds. There are 7 isoforms of viscotoxins from viscum album A1, A2, A3, B, B2, 1-PS and C1, with U-PS being an eighth more distantly related compound. Viscotoxins are hypothesized to interact with phosphatidylserine that is a prominent feature of cancer cells membranes, opening a hole in the cell membrane and destabilizing the DNA.<ref>{{cite journal | vauthors=((Samuelsson, G.)), ((Pettersson, B. M.)) | journal=European Journal of Biochemistry | title=The Amino Acid Sequence of Viscotoxin B from the European Mistletoe (Viscum album L, Loranthaceae) | volume=21 | issue=1 | pages=86–89 | date= 1971 | url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1432-1033.1971.tb01443.x | doi=10.1111/j.1432-1033.1971.tb01443.x | access-date=27 March 2023}}</ref><ref>{{cite journal | vauthors=((Pal, A.)), ((Debreczeni, J. É.)), ((Sevvana, M.)), ((Gruene, T.)), ((Kahle, B.)), ((Zeeck, A.)), ((Sheldrick, G. M.)) | journal=Acta Crystallographica Section D Biological Crystallography | title=Structures of viscotoxins A1 and B2 from European mistletoe solved using native data alone | volume=64 | issue=9 | pages=985–992 | date=1 September 2008 | url=https://scripts.iucr.org/cgi-bin/paper?S0907444908022646 | doi=10.1107/S0907444908022646 | access-date=27 March 2023}}</ref><ref>{{cite journal | vauthors=((Nawrot, R.)), ((Barylski, J.)), ((Nowicki, G.)), ((Broniarczyk, J.)), ((Buchwald, W.)), ((Goździcka-Józefiak, A.)) | journal=Folia Microbiologica | title=Plant antimicrobial peptides | volume=59 | issue=3 | pages=181–196 | date= 2014 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971460/ | doi=10.1007/s12223-013-0280-4 | access-date=27 March 2023}}</ref> Viscotoxins have been shown to act as an antimicrobial compound, specifically having anti-fungal activity.<ref>{{cite journal | vauthors=((Giudici, A. M.)), ((Regente, M. C.)), ((Villalaín, J.)), ((Pfüller, K.)), ((Pfüller, U.)), ((De La Canal, L.)) | journal=Physiologia Plantarum | title=Mistletoe viscotoxins induce membrane permeabilization and spore death in phytopathogenic fungi | volume=121 | issue=1 | pages=2–7 | date= 2004 | url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0031-9317.2004.00259.x | doi=10.1111/j.0031-9317.2004.00259.x | access-date=27 March 2023}}</ref> |
| + | Triterpine compounds have been isolated from mistletoe extracts. Betulinic acid is isolated from birch host tree mistletoe and exerts a multitude of anticancer effects, regulating JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in tumor cells.<ref>{{cite journal | vauthors=((Aa, F.)), ((A, T.)), ((G, T.)), ((A, T.)), ((A, B.)), ((G, K.)), ((S, A.)) | journal=Molecules (Basel, Switzerland) | title=Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis | volume=28 | issue=1 | date=21 December 2022 | url=https://pubmed.ncbi.nlm.nih.gov/36615262/ | doi=10.3390/molecules28010067 | access-date=2 April 2023}}</ref> Other triterpenes isolated from mistletoe extracts are b-amyrin acetate and oleanolic acid. As these are poorly water soluable the manufacturers use extraction techniques to enhance these compounds in their extracts. |