Biologically active compounds from European mistletoe (Viscum albumL.)¹

Abstract

European mistletoe (Viscum album L.) is a commonly occurring semiparasite of trees. The extracts from European mistletoe have been shown to possess immunostimulatory and cytotoxic activity on tumor cells, and are used in Europe in adjuvant cancer therapy. Recently, a number of studies performed have been leading to the identification and characterization of bioactive compounds. Apoptosis-inducing and ribosome-inactivating lectins as well as cytotoxic thionins (viscotoxins) are the main groups of compounds participating in biological activity of V. album. These compounds were isolated and studied in vitro and in vivo for their biological activity and mechanism of action. A comparison of the results to those using whole extracts indicated that lectins and viscotoxins are not the only bioactive compounds present in the mistletoe and among them, high heterogeneity is observed in both structure and activity. In this paper, we review the current state of the art in mistletoe studies, emphasizing its potential application as a drug, its standardization, and taxonomic problems. The nontherapeutic applications and suspected physiological functions of the compounds in question are also discussed briefly. Résumé : Le gui (Viscum album L.) est un semi-parasite commun des arbres. Les extraits du gui ont montré une activité immunostimulatrice et cytotoxique sur des cellules tumorales, et sont utilisés en Europe dans le traitement adjuvant du cancer. Récemment, plusieurs études ont conduit à l'identification et la caractérisation de composés bioactifs. Des lectines inductrices d'apoptose et inactivatrices de ribosomes ainsi que des thionines cytotoxiques (viscotoxines) sont les principaux groupes de composés qui contribuent à l'activité biologique du V. album Ces composés ont été isolés et étudiés in vitro et in vivo pour leur activité biologique et leur mécanisme d'action. La comparaison des résultats avec ceux obtenus avec des extraits complets indique que les lectines et les viscotoxines ne sont pas les seuls composés actifs présents dans le gui et, parmi ceux-ci, on observe une grande hétérogénéité de structure et d'activité. Dans le présent article, nous faisons le point sur les connaissances sur le gui, avec l'accent sur son potentiel d'utilisation comme médicament, sa normalisation et ses problèmes taxinomiques. Les usages non thérapeutiques et les rôles physiologiques présumés des composés en question sont aussi discutés brièvement.

Mistletoe viscotoxins induce membrane permeabilization and spore death in phytopathogenic fungi

“…Viscotoxins (Vts) are a group of basic cystein‐rich peptides of about 5 kDa that were isolated from different mistletoe species and are abundant in leaves and seeds (Ochocka and Piotrowski 2002). Six isoforms of Vts from the semi‐parasitic plant Viscum album are known, namely A1, A 2 , A 3 , B, 1‐PS and U‐PS (Orrù et al 1997).…”

Antifungal effects and mechanism of action of viscotoxin A3

“…Viscotoxins are small proteins of ≈ 5 kDa isolated from leaves, stems and seeds of European mistletoe ( Viscum album Loranthaceae). They belong to the thionin family type III and are characterized by the presence of three disulfide bridges [4,5]. The homology of viscotoxins to other thionins is restricted to the six cysteines in conserved positions (although there are also variants known from cDNAs that contain eight cysteines [6]) as well as an aromatic residue at position 13 and an arginine at position 10.…”

“…The homology of viscotoxins to other thionins is restricted to the six cysteines in conserved positions (although there are also variants known from cDNAs that contain eight cysteines [6]) as well as an aromatic residue at position 13 and an arginine at position 10. To date, seven variants, A 1 , A 2 , A 3 , B, C1, 1‐PS and U‐PS, have been described [5,7,8]; viscotoxin A 3 (VtA 3, Fig. 1A) is the most cytotoxic, whereas viscotoxin B (VtB) is the least potent [9,10].…”

Neurophysiological effects of mistletoe (Viscum album L.) on isolated rat intestines

“…cytotoxic effects of viscotoxins are weaker than of lectins (Urech et al, 1995), but mechanisms underlying these effects of viscotoxins are poorly understood (Ochocka and Piotrowski, 2002).…”