Next Article in Journal
Comparison of Different Green Extraction Techniques Used for the Extraction of Targeted Flavonoids from Edible Feijoa (Acca sellowiana (O.Berg) Burret) Flowers
Previous Article in Journal
Metabolomics Analysis Reveals Metabolites and Metabolic Pathways Involved in the Growth and Quality of Water Dropwort [Oenanthe javanica (Blume) DC.] under Nutrient Solution Culture
Previous Article in Special Issue
Effect of Ginseng Sapogenin Protopanaxadiol-Enriched Rice (DJ-PPD) on Immunomodulation
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

The Anti-Inflammatory Activity of Viscum album

Marcello Nicoletti
Department of Environmental Biology, Sapienza University of Rome, 00185 Rome, Italy
Plants 2023, 12(7), 1460;
Submission received: 14 February 2023 / Revised: 14 March 2023 / Accepted: 16 March 2023 / Published: 27 March 2023
(This article belongs to the Special Issue Natural Compounds in Plants and Their Anti-inflammatory Activity II)


The therapeutic story of European mistletoe (Viscum album L.) presents a seesawing profile. In ancient times, this hemiparasitic plant was considered a panacea and even to be endowed with exceptional beneficial properties. In more recent times, despite its multiple uses in traditional medicines, some parts of the plant, in particular the berries, were considered poisonous and dangerous, including concerns of cytotoxicity, which spread serious suspicion on its medicinal utility. However, since the last century, medical interest in mistletoe has come back in force due to its utilization in clinical cancer treatments, based on its selective action on tumor cells. In Central Europe, the hydro-alcoholic extracts of European mistletoe register a relevant and continuous utilization in anthroposophic medicine, which is a holistic system that includes the utilization of phytomedicinal substances. In Switzerland and Germany, most physicians and patients use these products as complementary therapy in oncological treatments. However, despite its increasing use in this field, the results of mistletoe’s use are not always convincing, and other aspects have appeared. Nowadays, products that contain mistletoe are utilized in several fields, including diet, phytotherapy, veterinary medicine and homeopathy, but in particular in cancer therapies as coadjuvant factors, in consideration of several positive effects including effects in the improvement of quality-of-life conditions and reinforcement of the immune system. In this review, based on the understanding of the association between cancer and inflammation, we propose a relationship between these recent uses of mistletoe, based on its antioxidant properties, which are supported by phytochemical and pharmacological data. The unicity of mistletoe metabolism, which is a direct consequence of its hemiparasitism, is utilized as a key interpretation element to explain its biological properties and steer its consequent therapeutic uses.

1. Introduction

Medical treatment of diseases is an open work in progress, being dependent not only on scientific evidence, but also on cultural, social, political, economic and other temporary influences. The history of medicine is full of more or less radical changes and difficulties in acceptance of revision in medical drugs and their utilization. This is particularly evident in the therapeutic use of medicinal plants. The controversial medical utilization of mistletoe throughout the centuries is here reported as a case study, focusing on the recent relation between inflammation and cancer, including effects on the immune system and general living condition.

1.1. Mistletoe (Viscum album L.), a Special Plant

Viscum album L. (Santalaceae, formerly Viscaceae or Loranthaceae) is the most common species of its genus (c. 450 species) [1], mainly present in Europe and Asia and commonly known as European mistletoe or simply mistletoe [2]. Viscum plants are an exceptional example of diversity in dicotyledonous angiosperms, though in their general appearance and morphology they are very similar to many other shrubs present in temperate flora [3]. It is an evergreen woody shrub, with stems 30–100 centimetres long characterized by abundant dichotomous branching. The entirety of the leathery strap-shaped leaves are yellowish-green in colour. This species is dioecious with inconspicuous, yellowish-green flowers, whereas the fruits are typical, as opalescent globose berries, containing a very sticky, glutinous pulp embedding one (very rarely several) seed [4].
Unicity of Viscum spp. concerns the physiology, since they are epiphytic and obligate hemiparasitic plants. They are completely wrapped inside the crowns of broad-leaves of the host, where they can be found by looking carefully. The obligate hosts are several deciduous and needle trees, such as apple, linden, hawthorn, oak and poplar, but also pines and firs, as well as shrubs, such as hawthorn, whereas mistletoe cannot be found in Fagus or Platanus species. However, the Viscum’s parasitism is dependent on the available flora, since in Nigeria and Ghana, it can be found on cocoa, kola and cashew trees [5].
In these regions, the mistletoe is evident as a denser prominent globose silhouette up to 1–2 m in diameter, distinguished by the rounded shape and deeper green colouration of the abundant leaves inside the crown of the tree host [6]. This is a consequence of its aerial hemiparasitism, consisting of the metamorphosis of the root system, which is converted into an endophytic haustorial organ structure that is able to enter inside the host’s tissue at the xylem level and suck water and nutritional substances contained in the sap [7]. This allows the plant to avoid any ground contact, and it is the cause of many anomalies. In fact, mistletoe is a common name for several independent lineages descended from sandalwood. As well, sandalwood species belonging to the same family Santalaceae are hemiparasites, but they insert sinker haustoria inside the host roots [8,9]. Unlike those ancestors, mistletoes do so in the sky. Especially in weather conditions with water stress, due to competition with the host tree, the parasitism of V. album can cause problems in the growth and vitality of the host [10,11]. However, under usual and favourable conditions, host trees are only moderately affected, and often both can coexist well [12,13].
Evidence of Viscum parasitism is hidden in its metabolism, characterized by an extraordinary life cycle and unique biochemical properties, based on a genome that is extremely large, estimated to be 600 times the genome of Arabidopsis thaliana [14], which is considered the model plant in angiosperms. In addition to reported distinct feature differences in the photosynthesis process, consisting of the different ultrastructures of chloroplasts and lower amounts of chlorophylls [15], attention has been focused on the particularities of the respiratory system. European mistletoe is the only known multicellular organism able to survive without the mitochondrial NADH dehydrogenase complex of the respiratory chain, which catalyses the electron transport chain essential for the production of the energy necessary to fuel cell metabolism. Its respiratory system, due to its restricted capacities to generate mitochondrial ATP, is believed to survive by relying to a great extent on obtaining energy provided by its host tree and on alternative respiratory enzymes [16,17].
Furthermore, studies on the photosynthetic apparatus of V. album [18] evidenced relevant differences in mitochondria and thylakoids in comparison with other angiosperms, including the corresponding changes in the genome due to adaptation [19]. In this case, it is possible to assume that V. album’s metabolic apparatus is tailored to interact with the cells of other organisms. However, these are not the only surprises. Viscum plants possess the ability to parasitise another mistletoe that has already parasitised a host tree. This rare facultative tripartite network is a form of special association named hyperparasitism. When mistletoe undergoes an obligate association with another species of mistletoe, it is better called epiparasitism. In the case where the parasite is a member of the same species, this is named autoparasitism [20]. The lesson is that the more we investigate and study the biological phenomenon called parasitism [21], the more we have to learn, which means our knowledge must be continually updated. This should be considered in all aspects concerning V. album, including its uses.
Among the evidences of this situation, the impressive variability and adaptability of V. album merit special consideration [22]. The total preference for evergreen hosts allows the plant to photosynthesise throughout the year and at low temperatures below the freezing point, although at a rate lower than the host’s assimilation organs. For the reasons already reported, the V. album species is subdivided into several subspecies and varieties, which are specialised according to the host tree or shrub [23]. Different from the common action, V. album rarely grows on oak trees, wherein it is substituted by another hemiparasite, Loranthus europeus Jacq. (Loranthaceae), the oak tree or yellow mistletoe. The two species are quite similar in shape but very different in chemical constitution, as evidenced by the metabolomic HPTLC analysis of bud extracts [24]. Therefore, in this case, the exact botanical identification, made by a specialist in botany, is necessary.
The relationship between mistletoe and its host, besides behaviour, primary metabolism and ecology, deeply affects the secondary metabolism as well [25,26]. Many studies evidenced a relevant interchange and influx of material and information between the metabolisms of the parasite and the host [27,28,29,30], as evidenced also by the characteristics of the haustorial system and the parasitism of selected aerial parts of the host [31]. As in other investigated cases of parasitism, the conclusion is that in these cases, parasite and host partly compart metabolism, giving rise to a fused complex dynamic system, such as those named superorganisms. A superorganism is a successful and efficient organization of different living organisms. They are everywhere, for instance plentifully in the human body, and they are the fuel of evolution, in contrast with the negative effects of selection struggle competition. The plant no has direct link to the substratum, and the ground properties cannot influence it directly. The host has an intermediate role, but both organisms have to face habitat challenges together.
Phytochemical studies have reported the typical large quantity of natural products in angiosperms [32]: terpenoids, including steroidal and acid triterpenes, glycosides of different types, phenols in a wide range of types, phenylpropanoids, coumarins, as well as several kinds of amino acids, minerals and others. As usual, most of them are already known constituents, but also new compounds were identified, including the absence of common alkaloids in favour of a small but relevant presence of a new class of unusual aminoalkaloids [33].
The highly complex chemical composition, fully confirmed by HPTLC analysis [24], and biological activity of mistletoe are the result of its special metabolism, which is the consequence of a mixture of biotic effects (mainly host tree) and abiotic environmental characteristics, influencing both parasite and host, but in a different way. A complete report of V. album secondary metabolites until 2000 can be found in [34]. Their identifications were obtained by the usual phytochemical techniques, but much more information is being obtained by further research based on metabolomics approaches [35,36]. The metabolic approach on Romanian V. album evidenced the predominance of flavonoids, amino acids and peptides and terpenoids, representing about 60% of all metabolites identified; however, among them, flavonoids were predominant, accounting for more than 30% of the total identified constituents [37]. Among these compounds, the utilization of over 250 primary and secondary in medicine, present in leaves, shoots and berries, has been reported [38]. Variations in quantity and quality were also observed for different compounds [39,40], including triterpenes [41] and antioxidants [42,43]. The highest levels of total phenolics, flavonoids and antioxidant effects of V. album were observed in the leaf extract compared with fruit and seed [44,45].
Special attention must be paid to specific oligoproteins in consideration of their biological activity [46]. The foliage and fruits of V. album, as in other related species, contain low-molecular-mass proteins of the thionin type, designated as viscotoxins, as well as characteristic lectins, named viscolectins, both of which are able to contribute to its defence system and can be found in related extracts and products. These classes of Viscum microProteins have received considerable attention because of their contribution to cytotoxic and immune-stimulating effects of the mistletoe extracts used in medicine, as later discussed, including their mechanism of action [47,48,49].
Several isoforms of viscotoxins have been reported, with A1, A2, A3 and B considered the predominant ones and usually measured in quality controls. Viscotoxin A3 is usually the predominant isoform [50,51,52,53,54] and also the most active, as confirmed by comparative membrane interactions [55]. However, the total proteome of thionins is much more complicated, and includes viscumin, reported as very active but present in very low quantity [56,57,58,59]. Viscumin is reported able to participate in in vitro activity, including inhibition of protein synthesis in a cell-free system, and pertains to the pull of thionins, and also is reported as responsible for cytotoxicity [60].
Lectins are well-known for their capacity of linkage to the sugar component of membrane cells (the name derives from the Latin word lego, meaning “to link”). The biochemistry and structures of three types of V. album lectins were studied and characterized, termed mistletoelectins I, II and III (MLI, MLII and MLIII) [61,62,63], evidencing their role as precursors to proteins and the structures based on two chains, post-translationally cleaved into an alpha and a beta chain. The two chains are stabilized by linkage via disulfide bridges [64]. The beta chain, in accordance with the lectin activity, specifically binds to sugar residues of membrane proteins, inducing its endocytic uptake by target cells. The alpha subunit has RNA glycosidase activity. The consequence is possible damage to the involved cells, thereby inactivating the ribosome and inducing apoptosis [65]. However, further studies that focused on clarifying this aspect have shown that “direct apoptosis induction by mistletoe lectins occurs only after uptake of the molecules into the cell due to the action of the ribosome inactivating A-chain”, meaning there is no evidence for cytotoxic effects caused by isolated A- and B-chains [66,67].
Considering that most of the organic matter of any living organism is made of proteins (c. 80%), the content in marketed products of European mistletoe, used as food or for therapeutic uses, could appear irrelevant, being in the order of few mg/g of dry material for viscotoxins and even ng/g for viscolectins, but they have attracted great interest for their specific biological activity. However, most of the metabolome is made by large high-molecular weight proteins inside the structural network of the organism, whereas microProteins, are small, less than 20 KDa, and contain a single domain [68,69]. This domain allows plant microProteins to interact with other compatible domains of evolutionary-related proteins and perform specific key physiological effects in several organisms. In particular, microProteins are recently under deep investigation, in consideration of their role in plant development [69,70]. Viscotoxins are cationic cysteine-rich proteins composed of only 45 amino acids and with a molecular weight less than 5 KDa [67].
The presence and content of Viscum microProteins, and therefore their content in related marketed products, is subject to several variations. Although the foliage (meaning leaves, little branches and shoots when present) content is higher than the fruit one, again the percentage is subject to high variation in relation to the subspecies, the host, the season and the ecological conditions [70], assigning importance to the harvesting time. It is expected that the pharmacological activities of mistletoe extracts, such as cytotoxicity and induction of apoptosis in cancer cells, vary accordingly.
The anticyclic timing of leaf senescence and abscission in mistletoe, which occurs in the summer, has been observed, when on the contrary the metabolic activity in the host has reached its maximum [71]. It is possible that viscotoxins play a significant role, since in that period they only degrade, whereas most of the remaining leaf proteins are lost during abscission, and the changes in viscotoxin content are similar to changes in the concentration of the corresponding mRNA; however, shortly before the onset of leaf senescence, the mRNA for viscotoxin disappears from the leaves [72]. These are additional signs of the exceptional biological activity of the microProteins of V. album.
Further information came from the study of viscotoxins production. In 2022, Schroder et al. [73] deeply examined the genome of V. album, reporting new insights into the metabolism and molecular biology of the plant, including the biosynthesis of lectins and viscotoxins. Considering the paradox of the extremely large genome and the low dimension of produced proteins, they focused their attention on the analysis of the sequencing of the V. album gene space (defined as the space including and surrounding genic regions, encompassing coding as well as 50 and 30 non-coding regions). The analysis of the mitochondrial genome allowed them to evidence that the V. album gene space includes a transcript encoding the enzyme L-galactono-1,4-lactone dehydrogenase (GLDH). GLDH is localized in the mitochondrial intermembrane space and catalyses the terminal step of the mitochondrial ascorbate biosynthesis pathway [74]. This information could be related to the selective action of V. album extracts on cancer cells, as further discussed. The paper is an example how the introduction of new potent analytical techniques and tools, such as hyphenated approaches including HPLC-MS/MS [75,76], can be fundamental in obtaining reinterpretations of biological effects, so far hastily catalogued. Several authors also argue the necessity of opening the consideration of the constituents considered responsible of the activity of V. album extracts, including the toxic effects, and avoiding focusing the total attention on microProteins [77].

1.2. The Controversial Medical Story of Mistletoe

According to Luther and Becker, European mistletoe has been studied for more than 2000 years, in particular for its medicinal uses [78]. Some features remained practically the same through the centuries, whereas other ones changed [79]. Since ancient times, European mistletoe’s therapeutic properties, such as antidiabetic, analgesic, anti-inflammatory, anti-arrhythmia and hypotensive properties, were already known in popular and traditional medicines of Europe, Asia and Africa, and are still well present in the medicines of several countries [80,81,82,83,84,85]. In the Occident, as many other medicinal plants, after the old periods of practice in popular medicine, it suffered a long period of obscurity and prevention of use, until a recent renaissance [86].
Mistletoe is generally known as a talisman of good fortune and prosperity. In fact, it has long been considered a pagan religious symbol of prosperity and was believed to have magical properties. The use of mistletoe in ritual form is mainly related to traditions of Celtic druids, the ancient civilisation of people living on the British Isles, in what is now Ireland and Scotland [87]. The Roman historian Plinius Secundum (23–79 AD) reported that druids mainly used mistletoe, collected on the oak, as a panacea (“Viscum” which should mean “able to cure any disease”), and considered it to be a sacred plant [88]. However, Greeks and Romans did not believe the mistletoe’s healing powers, as with everything coming from “Barbarians”, as reported by Plinius: “They believe that mistletoe, taken in potion, gives the ability to reproduce to any sterile animal, and that it is a remedy against all poisons: so great is the devotion that certain peoples turn to things mostly of no importance” (translated by the author). On the contrary, in Viking sagas, the plant is related to the death of Baidr (or Baldur), grandson of the Norse god Thor, stabbed and killed by an arrow made from the wood of a mistletoe plant [89]. In any case, the conquest of Gaul by Julius Caesar erased any Celtic cultural heritage and obliterated the ancient knowledge of druids, including the complex procedures to select, collect and use mistletoe. Consequently, the healing properties of mistletoe were obscured for centuries, whereas the poisonous effects of eating berries became dominant. The original name changed to mean a substance that is gooey, adhesive and gluey, as the pulp of the berry once used to trap birds; however, in the plant, the sticky pulp, made by hemicelluloses, is necessary for the dissemination made by birds, since the seeds do not germinate in soil and in this way stably attach themselves to the bark branches of the tree, making possible the growth of new plants [89,90].
However, reading carefully the documents of scholars through the Middle Ages, including the Dioscorides De Materia Medica, the healing properties of European mistletoe preparations are always reported. Hippocrates recommended its use to treat diseases of the spleen and complaints associated with menstruation. Paracelsus described its benefits in the treatment for epilepsy. Hildegard von Bingen considered mistletoe as useful in the treatment of diseases of the spleen and liver. Moreover, ethnobotanical studies evidence a wide range of continuous uses in the popular medicine of every part of the world wherein plants of the Viscum genus are present, without evidence of very rare adverse effects [91].
As a matter of fact, for a long time in the textbooks of botany and pharmacognosy, mistletoe was considered an extravagantly dangerous invention of nature, and by the end of the nineteenth century, mistletoe was rejected by scientists, and retreated as a folklore remedy, although mistletoe was also commonly used in the medicines of other parts of the world, including Japan, Israel and several African countries [92,93,94]. This remained the case until a century ago, when something changed [95].
In 1920, Rudolf Steiner introduced V. album in cancer treatment as a drug extract, obtained by a complicated manufacturing process, combining sap from mistletoe harvested in winter and summer [86]. Rudolf Steiner (1861–1925) was an Austrian scientist and philosopher considered the founder of anthroposophic medicine, together with Ita Wegman [96]. Thereafter, the use of Viscum extracts in medicine increased, in particular in the countries of Central Europe [97]. During the last years, the antitumor activity of V. album preparations has been reported and checked in many clinical reports from 1919, with potential effectiveness in the treatment of neuroblastoma [98] and other cancer cases [99,100]. Viscum preparation was used in clinical combined therapy of advanced metastatic cancers [101,102,103,104,105,106,107,108,109], whose effects were mainly attributed to viscotoxins and viscolectins.
The first concern of physicians was the evidence of absence of toxic and adverse effects, meaning safety in the treatment. The results were encouraging [110,111], but, in continuing the therapies, the attention of physicians working in the hospitals was attracted by other effects, concerning the improvement of the quality of life of patients under conventional and palliative oncological treatments [112,113,114], registering the reduction of serious collateral effects of chemotherapy in treatment of several tumor cases, including breast, ovarian, non-small cell lung cancers and, on the contrary, the evidences of beneficial effects [115,116] were increasing and the attention shifted, changing again the perspective.
Nowadays, despite the high number of reported positive cases, including better survival [117,118,119,120,121,122,123,124], the cure for cancer using V. album is considered not totally valid and its effectiveness is under discussion [125,126,127]. However, it has to be admitted and added that at the present there are not totally sure and effective medical solutions to free humanity from cancer. However, the observation about the use of V. album commercially available products as adjuvants appeared significant in number and quality, and related to the improvement of the immunoadjuvanten and immunomodulating properties in a dose-dependent way [128,129,130,131,132,133], influencing the dendritic cells and showing other effects [134].

1.3. The Anti-Inflammatory Properties of Mistletoe

The utilization of V. album in cancer therapy was reinforced by several studies, which evidenced the character of the cytotoxic action of microProteins of V. album by several pharmacologic tests selectively directed at cancer cells, utilizing the capacity to link to membrane sugar and clarifying the absence of severe adverse effects during the treatments [135]. On the other hand, the positive effects during the treatments need to be explained and assigned to some other activities of Viscum products, including their anti-inflammatory activities.
The anti-inflammatory properties of V. album preparations and marketed products have been reported. The activity was supported by evidence on effects on many factors related to the inflammation process. In particular, the constituents of V. album were investigated for COX-2 inhibitory effect, selective inhibition of cytokine-induced expression of cyclooxygenase, mediated PGE2 and COX-2 inhibition implicating COX-2 mRNA destabilization [136,137,138].
In many papers, the anti-inflammatory activity was reported in connection with other activities, including the antioxidant [139,140,141,142,143,144] and anticancer [145,146,147]. Among the constituents of V. album, besides microProteins [148], other constituents, i.e., phenols and in particular flavonoids, have been considered responsible for this activity [36,143,149,150], in consideration of their well-known anti-ROS and radical-scavenger properties [151], and of the isolation of new flavonoids in V. album [152,153]. Most of the studies amplified the research to other constituents to evidence how they may co-operate in the activity [149,150,151,152,153,154,155,156], including new phenolic compounds isolated from the whole plant [157]. In several papers, more activities are considered on the basis of a connection made between inflammation and many related pathologies [157,158,159,160,161,162,163,164,165,166,167,168,169,170]. In the medical point of view, inflammation is divided into acute and chronic inflammation, according to causes, symptoms and medical treatment. Another important aspect is the age of the patient and the different immunological tasks. The aim of the treatment of the acute inflammation is focused on elimination of responsible agents, such as antigens, viruses, bacteria, etc., whereas in chronic inflammation the catabolic and destructive aspects are predominant, and therefore therapy is focused on restoring the homeostasis of the organism.
In Table 1, the reported studies on anti-inflammatory activity of V. album extracts and derived products (VA) are reported. Due to the paramount utilization of VA products in oncology and connected palliative and adjuvant therapies, most of the studies are dedicated to supporting the efficacy of these treatments. As a consequence, the extracts, or directly the products, were utilized. In most cases, further investigations concerning the analysis of active constituents are necessary. However, several reports evidence in deep detail the related mechanisms and factors. In consideration of the related activity, in Table 2 the reports concerning the antioxidant activity are reported. Again, most of the studies concern the registration of the activity, including radical-scavenger properties, without the necessary analysis of the substances responsible of the properties, insisting on total phenolic content and obsolete tests. This is the consequence of a limited approach in the study of medicinal plants, wherein phytochemists and pharmacologists independently conduct their work, whereas a complete interaction is necessary. The metabolomics approach is causing a revolution in the phytochemical analysis and pharmacology should change, in accordance. The future of phytomedicines relies on this challenge.
Most of the studies concerning the anti-inflammatory activity of V. album may be evaluated on the hypothesis that the inflammation is basically an automatic reaction of the body to any kind of deviation from the homeostatic state [173]. As consequence of an external attack, such as an infection or an injury, or an internal dysfunction, such as an auto-immune or tumor disease, inflammation is in charge of activating the physiological processes indispensable to restart or maintain the homeostasis. However, chronic inflammation is a common accomplice of disease. Therefore, inflammation is on one side related to the cause and on the other side to the connected reaction to the disease, either a signal, a replay or a pathologic state. Nowadays, the medical treatments are dedicated to the signals, meaning the boring and debilitating state, and consist mainly in removing the symptoms, meanwhile waiting for the immune system to do its job and restore the homeostatic condition [174,175]. In many cases, as in most infections, this coupling works perfectly in a few days, otherwise the magic pill results are not sufficient and another approach is necessary, considering all the required aspects. In cases of research on the antioxidant and anti-inflammatory activities of V. album, the tendency is in favour of connecting inflammation to the pathology and considering every possible effect. To obtain this result, the utilization of mixes of active substances is considered necessary, due to the multiple targets. In accordance with the phytocomplex approach, any plant extract contains many different substances with different activity. In this regard, the antibacterial activity must also be considered since bacteria are also one of the intrinsic and extrinsic factors that can cause inflammation cancer, and the antimicrobial activity has been connected with antitumor properties [176,177,178,179,180,181]. The utilization of V. album preparations in the treatment of cancer and anti-inflammatory activity can now be used as a case study.

1.4. Inflammation and Cancer

In war, the first immediate measure is to kill as many enemies as possible with the best available weapon, without concern about the consequences. Consequences always come. In the report of February 2022, WHO stated that cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. Cancer is considered the second main cause of death, after cardiovascular diseases [182]. For a long time, the main therapies of cancer have been directed at the target, as selectively as possible, consisting in destroying any cancer cells by surgery, chemotherapy, radiation therapy, hormone therapy and/or immunotherapy. A key problem concerns the selectivity. Most of conventional cancer treatments suffer from severe off-target effects, as a consequence of sharing critical facets of cells, generally targeted by all rapidly proliferating capacity. The WHO also stressed the importance of improving the patient’s quality of life as a fundamental goal, which can be achieved by support for the patient’s physical, psychosocial and spiritual well-being, including palliative care in terminal stages of cancer in connection with other drugs.
It is well-known that cancer treatments can be devastating for the patient, who absolutely needs support, to be able to face the impact of the disease and the cure. Furthermore, the immune system must be in a condition to play its fundamental role. Consequently, the so-called cocktails of drugs are increasingly utilized to treat cancer, as well as other impacting diseases. New therapeutic agents are urgently required to increase selectivity, help the immune system, reduce side-effects and support general health conditions.
The relation between cancer and inflammation has been widely demonstrated. As recall by Pushpa Hegde, “inflammation and cancer dance together towards disaster”. Inflammation is considered a hallmark of cancer, and related to the spread of the disease within the body and the resistance of cancer cells to the treatment. Chronic inflammation is closely related to oxidative stress and immunosuppression [183,184,185,186,187,188,189].
Cancer development is dependent on inflammation, since when cancer causes necrosis of healthy cells, they release cell contents into the environment, triggering the release of pro-inflammatory mediators [190]. Further, the responses to therapy are regulated by inflammation, which either promotes or suppresses cancer progression [191], together with the general life conditions and the ability to promote an immune response [192].
Among the properties of the neoplastic cells to resist cancer treatment, the altered lipid metabolism, and consequently the abnormal cell membrane composition, plays a central role. Changes are necessary to the accumulation of energetic material, which could be used for a higher proliferation rate, obtained by the modulation of certain enzymes [193]. Consequently, some biophysical properties of cell membranes, namely, the composition of cell membranes in tumor cells, leads to cancer biomarkers, a higher resistance to chemotherapy and finally to the response of the immune system. Particularly interesting is the significance of the cell membrane content in the modulation of metastasis [194]. Clinical studies show novel therapeutic options concerning the modulation of cell membranes in oncology [195,196].
To understand the possible role of antioxidant and anti-inflammation of constituents of V. album in the fight against cancer and other diseases, it is necessary to inter-cross the information about the four items so far considered: cancer, inflammation, immune system and metabolome.

2. Conclusions

Although further data trials need to be performed, the examination of clinical and pharmacological evidence on the majority of oncological patients so far allows us to consider European mistletoe extracts able to cause various anticancer achievements [197,198,199,200]. This anticancer activity is matched with pro-apoptotic, antiproliferative and immunomodulatory effects, which are considered necessary to reduce the disease. They are joined with treatment-related symptoms and in condition to improve the health-related quality of life.
Once the cytotoxic activity of microProteins, i.e., viscotoxins and viscolectins, was discovered, the problem of the mechanism of activity of V. album preparations was solved [79]. However, the belief that these peptides are unstable when ingested led to their administration by subcutaneous injection. The persistence of activity in oral prescriptions, as well their use in complementary medicine, changed some perspectives on this point. Thanks to new analytic methods based on hyphenated instrumentations, it is now evident that the proteome of V. album is much more complicated [201,202,203,204].
It is now possible to organize all of the aforementioned pieces of information to depict a coherent framework. V. album, in the form of hydro-alcoholic extract of foliage and fruits, can exert a selective cytotoxic activity against cancer cells, as evidenced by several studies. In particular, de Oliveira Mello, studying the phenolic compounds from V. album tinctures, which enhanced antitumor activity in melanoma murine cancer cells [205], investigated the toxicity of hydro-alcoholic extracts of V. album on different cell lines to assess their selectivity. The results are evident, since the control tinctures decreased the viability of B16F10 cells (murine melanoma) and the K562 (human chronic myelogenous leukemia cell line) in a dose-response way, where B16F10 presented a higher sensitivity. On the contrary, the MA-104 cell line, consisting of a normal cell line (monkey kidney, non-tumoral), resulted in resistance to all hydro-alcoholic concentrations used. The conclusion, on the basis of the reported data, is that V. album preparations obtained by hydro-alcoholic extraction of V. album, showed a selective tumor cytotoxicity with apoptosis induction and cell cycle effect. The next rational step consists of the detection of the substances responsible for the selective action, including microProteins and phenols.
Zarković et al. [206] reported that low concentrations of V. album commercial extracts (Isorel) inhibited B16F10 and HeLa tumor cell lines, and the observed effects resulted more strongly than purified lectin-1. Therefore, the authors considered that the therapeutic effect of the tested commercial preparation Isorel must be assigned to the association of low and high molecular weight components present in the extracts. Other authors share this interpretation. However, the general pharmacological idea, derived from the magic bullet axiom, is that one substance, or several substances that are structurally similar, must be investigated as responsible for a specific activity. The phytocomplex concept works with the opposite interpretation. Further confirmation about the bioactivity of other constituents came from the study of activity of flavonoid and phenolic acid constituents, which were examined by molecular docking and dynamic simulations and showed a stable interaction with target proteins and drug-likeness properties [207].
The study of de Mello also showed selective evident changes in the plasma membrane of the tumoral cell lines after treatment with the hydro-alcoholic extracts [208]. The plasma membrane is fundamental for the exchange of materials, as well the attack on the cell by external factors. This activity is derived from the capacity to selectively link to components of the membrane lipids, carbohydrates and proteins, which are characteristic constituents of cancer cells.
If we assume that the V. album extracts display their action as a phytocomplex, wherein besides the microProteins such as viscotoxins and viscolectins, many other constituents can take part in the main property, including antioxidant, anti-inflammatory and anti-stress activity, this contributes to the general actions in restoring or maintaining homeostasis. The immunoadjuvanten and immunomodulatory properties fully confirm the capacities of V. album, in accordance with the ancient ethnobotanical indications and as in line with modern medical approaches [209,210,211,212,213,214,215,216].
Although a further study has confirmed the selective action of V. album extracts on cancer cells, leaving no effects on the normal ones [217] and fully confirming the observation of clinical trials about safety, as with any active substance, attention must concern about dosage [218,219]. As in any medicinal drug, the dose is a key factor. Concentrated products can cross the red line between benefit and damage. As a matter of fact, the number of scientific publications concerning V. album preparations increased exponentially in the last ten years, accordingly with interest in the therapeutic uses of derived products, which are widespread in food, food supplements and botanicals, with prevalence for phytomedicines in treatment of degenerative joint disease and as a palliative for malignant tumors in the form of extracts, such as Iscador, Isorel, Eurixor, Plenesol, Vysorel, Lektinol, Helixor, Cefalektin, ABNOVAviscum and Lektinol, again with positive results in safety and survival. Therefore, the concentration of active substances in these preparations must be considered safe, but there are also several concerns about the utilization in higher concentrations of some constituents, including microProteins. These compounds are known to produce dose-dependent hypertension or hypotension, bradycardia and increased uterine and gastrointestinal motility. However, the published literature on the human toxicity of mistletoe-containing products indicates that the majority of patients evidenced good tolerability and remained asymptomatic, with no reported deaths [111,129,130,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236].
Furthermore, veterinary medicine and/or homeopathy are the most promising fields for future applications [237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257,258,259,260,261], not excluding the antiviral properties, which ask for further continuous attention [262]. Therefore, the knowledge about European mistletoe properties is in continuous evolution and requires a continuous revision of its use in evidence-based complementary and alternative medicine [263,264,265,266].
The absence of serious adverse effects is confirmed by hundreds of reports of pharmaco-phyto-vigilance, although in many cases there are local collateral effects, such as rush, itching, low fever and eczema when the drug is administrated by subcutaneous injection (i.e., Iscador e AbnobaVISCUM) [267,268,269,270,271].
The experiences obtained from the utilization of V. album extract as a complementary and adjuvant drug against cancer encourage its utilization in other fields, including the production of products that are viscotoxin-free but still useful against inflammation [272], which must be validated by further studies and research.
In conclusion, V. album, in the form of hydro-alcoholic extract of foliage and fruits, exerts a selective cytotoxic activity against cancer cells. The activity is derived from the capacity to selectively link to the membrane proteins, which have a characteristic constitution in cancer cells [273]. Once linked, the active substances should be able to interact with the metabolism of the cancer cells and also with the microenvironment surrounding the cells, which can be the cause of the disease but in any case is involved in its development, including the inflammation effects [274].
This suggests a selective additional possible mechanism in induced apoptosis, through the binding to certain cell receptors, as in some human galectins [275]. Galectins are a small family of proteins containing carbohydrate-binding proteins. Although only 15 members are known so far, they are involved in many widespread physiological processes, such as inflammation, immune responses, fibrosis, autophagy, signalling and heart disease, as well as progression of metastasis of cancer. In addition to the aforementioned viscumin [276,277,278,279], more attention could be focused on other viscolectins, such as Viscum album agglutinin (VAA), which exerts various biological effects along with the cytotoxic properties for tumor cells in culture [142,171,280]. The activity of VAA was considered similar to galectin-1 [281,282]. Galectins, which are extracellular endogenous lectins, possess galactose-specific surface-binding sites. Galectins are well studied glycan-binding proteins, which mediate multiple biological functions, including immunity and anti-inflammatory effects, and have been shown to stimulate natural killer cells, granulocytes [283]. Noncytotoxic concentrations of VAA-I enhanced several anti-inflammatory effects, such as secretion of pro-inflammatory cytokines in cultures of human peripheral blood mononuclear cells, peripheral blood lymphocytes (PBL), human peripheral blood monocytes (PBM), murine thymocytes and human monocytic, and in an animal model VAA-I [284,285].
The V. album extracts display their action as phytocomplex, wherein besides the microProteins such as viscotoxins and viscolectins, they act with extracellular signal-regulated enzymes [286,287], as well many other constituents that can take part in the main property, antioxidant, anti-inflammatory and anti-stress activity, which contributes to the general actions in restoring or maintaining homeostasis. Particular attention should be concentrated on the constituents of the metabolome, including the discovery of new active constituents that are very different from microProteins [288]. The experiences regarding the utilization of European mistletoe extracts as a complementary and adjuvant drug against cancer encourage its utilization in other fields, which must be validated by further studies and research on the properties of this very special plant, as evidenced by recent publications [50,289].


This research received no external funding.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created.

Conflicts of Interest

The author declares no personal circumstances that may be perceived as inappropriately influencing the representation or interpretation of the reported considerations.


  1. Bremer, B.; Bremer, K.; Chase, M.W.; Reveal, J.L.; Soltis, D.E.; Soltis, P.S.; Stevens, P.F. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG II. Bot. J. Linn. Soc. 2003, 141, 399–436. [Google Scholar]
  2. Christenhusz, M.J.M.; Fay, M.F.; Chase, M.W. Plants of the World; Kew Publishing Royal Botanical Kew; The University of Chicago Press: Chicago, IL, USA, 2017; pp. 426–427. [Google Scholar]
  3. Büssing, A. (Ed.) Mistletoe, The Genus Viscum (Medicinal and Aromatic Plants-Industrial Profiles); Harwood Academic Publishers, CRC: Amsterdam, The Netherlands, 2000. [Google Scholar]
  4. Zube, D. Biological flora of Central Europa: Viscum album L. Flora 2004, 199, 181–203. [Google Scholar] [CrossRef]
  5. Oluwaseun, A.A.; Ganiu, O. Antioxidant properties of methanolic extracts of mistletoe (Viscum album L.) from cocoa and cashew trees in Nigeria. Afr. J. Biotechnol. 2008, 7, 3138–3142. [Google Scholar]
  6. Pfiz, M.; Kuppers, M. Dense crowns of the hemiparasitic mistletoe Viscum album exhibit shrub-like growth and high dry matter turnover. Flora 2010, 205, 787–796. [Google Scholar] [CrossRef]
  7. Thoday, D. The austorial system of Viscum album. J. Exp. Bot. 1981, 2, 1–19. [Google Scholar] [CrossRef]
  8. Chase, M.W.; Reveal, J.L. A Phylogenetics classification of the land plants to accompany APG-III. Bot. J. Lin. Soc. Lond. 2009, 161, 122–127. [Google Scholar] [CrossRef]
  9. Fineren, B.A. Root Parasitism in Santalaceae. Nature 1963, 197, 65. [Google Scholar] [CrossRef]
  10. Geils, B.W.; Hawksworth, F.G. Damage, effect and importance of dwarf mistletoes. In Mistletoes of North America Conifers; USDA: Washington, DC, USA, 2002; pp. 57–65. [Google Scholar]
  11. Noetzli, K.P.; Sieber, T.N. Impact of population dynamics of white mistletoe (Viscum album ssp. abietis) on European silver fir (Abies alba). Ann. For. Sci. 2003, 60, 773–779. [Google Scholar] [CrossRef] [Green Version]
  12. Briggs, J. Mistletoe, Viscum album (Santalaceae), in Britain and Ireland; A discussion and review of current status and trends. Br. Ir. Bot. 2021, 3, 419–454. [Google Scholar] [CrossRef]
  13. Briggs, J. Mistletoe-distribution, biology and the National Survey. Br. Wildl. 1999, 7, 75–82. [Google Scholar]
  14. Novak, P.; Guignard, M.S.; Neumann, L.J.; Mlinares, J.; Koblizkavà, A.; Dodsworth, S.; Kovaric, A.; Pellicer, J.; Wang, W.; Maca, J. Repeat-sequence turnover shifts fundamentally in species with large genomes. Nat. Plants 2020, 6, 1325–1329. [Google Scholar] [CrossRef]
  15. Hudák, J.; Lux, A. Chloroplast ultrastructure of semiparasitic Viscum album L. Photosynthetica 1986, 20, 223–224. [Google Scholar]
  16. Senkler, J.; Rugen, N.; Eubel, H.; Hegermann, J.; Braun, H.P. Absence of Complex I Implicates Rearrangement of the Respiratory Chain in European Mistletoe. Curr. Biol. 2018, 28, 1606–1613. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Maclean, A.E.; Hertle, A.P.; Ligas, O.; Bock, R.; Balk, J.; Meyer, E.H. Absence of complex I is associated with diminished respiratory chain function in European mistletoe. Curr. Biol. 2018, 28, 1614–1619. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Schroder, L.; Hegermann, J.; Pille, P. The Photosynthesis Apparatus of European mistletoe (Viscum album). Plant Physiol. 2022, 190, 1869–1914. [Google Scholar] [CrossRef]
  19. Petersen, G.; Cuenca Navarro, A.; Moller, I.M.; Moller, I.M. Massive gene loss in mistletoe (Viscum, Viscaceae) mitocondria. Sci. Rep. 2015, 5, 17599. [Google Scholar] [CrossRef] [Green Version]
  20. Ahmed, Z.; Dutt, H.C. Restriction of Viscum album to Few Phorophytes in a Habitat with Diverse Type of Three Species. Austin J. Plant Biol. 2015, 1, 1010. [Google Scholar]
  21. Nicoletti, M. Insect-Borne Diseases in the 21st Century; Academic Press: London, UK, 2020. [Google Scholar]
  22. Barney, C.W.; Hansksworth, F.G.; Geils, B.W. Hosts of Viscum album. Eur. J. For. Pathol. 1998, 28, 187–208. [Google Scholar] [CrossRef]
  23. Walas, Ł.; Kędziora, W.; Ksepko, M.; Rabska, M.; Tomaskewski, D.; Thomas, P.A.; Wòjcik, R.; Iszkulo, G. The future of Viscum album L. in Europe will be shaped by temperature and host availability. Sci. Rep. 2020, 12, 17072. [Google Scholar] [CrossRef]
  24. Piterà, F.; Nicoletti, M. Gemmotherapy, and the Scientific Foundations of a Modern Meristemotherapy; Cambridge Scholars Publishing: Newcastle upon Tyne, UK, 2020; pp. 402–406. [Google Scholar]
  25. Escher, P.; Eiblmeier, M.; Hetzger, I.; Rennenberg, H. Seasonal and spatial variation of carbohydrates in mistletoes (Viscum album) and the xylem sap of its hosts (Populus × euamericana and Abies alba). Physiol. Plant. 2004, 120, 212–219. [Google Scholar] [CrossRef]
  26. Ture, C.; Bocuk, H.; Asan, Z. Nutritional relationships between hemiparasitic mistletoe and some of its deciduous hots in different habitats. Biologia 2010, 65, 859–867. [Google Scholar] [CrossRef] [Green Version]
  27. Escher, P.; Eibimeier, M.; Rememberg, H. Differences in the influx of glutamine and nitrates into Viscum album from the xylem sap of its hosts. Plant Physiol. Biochem. 2004, 42, 739–744. [Google Scholar] [CrossRef] [PubMed]
  28. Escher, P.; Rennenberg, H. Influx of double labelled glutamine into mistletoe (Viscum album) from the xylem sap of its host (Abies alba). Plant Physiol. Biochem. 2008, 44, 890–894. [Google Scholar]
  29. Okubamichael, D.; Griffiths, M.E.; Ward, D. Host specificity, nutrient and water dynamics of the mistletoe Viscum rotundifolium and its potential host species in the Kalahari of South Africa. J. Arid Environ. 2011, 75, 898–902. [Google Scholar] [CrossRef]
  30. Escher, P.; Eibimeier, M.; Hetzer, I.; Rennemberg, H. Seasonal and spatial variations of reduced sulphur compounds in mistletoe (Viscum album) and the xylem sap of its hosts (Populus euroamericana and Abies alba). Physiol. Plant. 2002, 117, 72–78. [Google Scholar] [CrossRef]
  31. Skrypnik, L.; Maslennikov, P.; Feduraev, P.; Pungin, A.; Belov, N. Changes in Antioxidative Compounds and Enzymes in Small-Leaved Linden (Tilia cordata Mill.) in Response to Mistletoe (Viscum album L.) Infestation. Plants 2021, 10, 1871. [Google Scholar] [CrossRef]
  32. Nazaruk, J.; Orikowki, P. Phytochemical profile and therapeutical potential of Viscum album L. Nat. Prod. Res. 2016, 30, 373–395. [Google Scholar] [CrossRef]
  33. Amer, B.; Juvik, O.J.; Dupont, F.; Francis, G.W.; Fossen, T. Novel aminoalkaloids from European mistletoe (Viscum album L.). Phytochem. Lett. 2012, 5, 677–681. [Google Scholar] [CrossRef]
  34. Pfuller, U. Chemical constituents of European Mistletoe Viscum album L. In The Genus Viscum (Medicinal and Aromatic Plants-Industrial Profiles; Bussing, A., Ed.; Harwood Academic Publishers, CRC: Amsterdam, The Netherlands, 2000; pp. 101–122. [Google Scholar]
  35. Jager, T.; Holandino, C.; Rehman, M.N.; Condori Penazola, E.M.; Oliveira, A.P.; Garrett, R.; Glauser, G.; Grazi, M.; Ramm, H.; Urech, K.; et al. Metabolomic by UHPLC-Q-TOF reveals host tree-dependent phytochemical variation in Viscum album L. Plants 2021, 10, 1726. [Google Scholar] [CrossRef]
  36. Urech, K.; Baumgartner, S. Chemical constituents of Viscum album L.: Implications for the pharmaceutical preparation of mistletoe. Transl. Res. Biomed. 2015, 4, 23. [Google Scholar]
  37. Segneanu, A.-E.; Marin, C.N.; Herea, D.D.; Stanusoiu, J.; Muntean, C.; Grozescu, J. Romanian Viscum album, L.-Untargeted Low-Molecular Metabolomic Approach to Engineered Viscum-AuNPs Carrier Assembly. Plants 2022, 11, 1820. [Google Scholar] [CrossRef] [PubMed]
  38. Song, C.; Wei, X.-Y.; Qiu, Z.-D.; Gong, L.; Chen, Z.-Y.; Ma, Y.; Shen, Y.; Zhao, Y.-J.; Wang, W.-H.; Lai, C.-J.-S.; et al. Exploring the resources of the genus Viscum for potential therapeutic applications. J. Ethnopharmacol. 2021, 277, 114233. [Google Scholar] [CrossRef] [PubMed]
  39. Becker, H.; Exner, J. Comparative Studies of Flavonoids and Phenylcarboxylic Acids of Mistletoes from Different Host Trees. Z. Pflanzenphysiol. 1980, 97, 417–428. [Google Scholar] [CrossRef]
  40. Ochocka, J.R.; Piotrowski, A. Biologically active compounds from European mistletoe (Viscum album L.). Can. J. Plant Pathol. 2002, 24, 21–28. [Google Scholar] [CrossRef]
  41. Wójciak-Kosior, M.; Sowa, I.; Pucek, K.; Szymczak, G.; Kocjan, R.; Luchowsli, P. Evaluation of seasonal changes of triterpenic acid contents in Viscum album from different host trees. Pharm. Biol. 2017, 55, 1–4. [Google Scholar] [CrossRef] [Green Version]
  42. Pietrzak, W.; Nowak, R. Impact of Harvest Conditions and Host Tree Species on Chemical Composition and Antioxidant Activity of Extracts from Viscum album L. Molecules 2021, 26, 3741. [Google Scholar] [CrossRef]
  43. Szurpnicka, A.; Zjawiony, J.K.; Szterk, A. Therapeutic Potential of Mistletoe in CNS-Related Neurological Disorders and the Chemical Composition of Viscum Species. J. Ethnopharmacol. 2019, 231, 241–252. [Google Scholar] [CrossRef]
  44. Önay-Uçar, E.; Karagöz, A.; Arda, N. Antioxidant activity of Viscum album ssp. album. Fitoterapia 2006, 77, 556–560. [Google Scholar] [CrossRef]
  45. Simona, V.; Rugina, D.; Socaciu, C. Antioxidant activities of Viscum album’s leaves from various host trees. Bull. Univ. Agric. Sci. Vet. Med. Cluj Napoca Agric. 2008, 65, 327–332. [Google Scholar]
  46. Pal, A.; Debreczeni, J.E.; Sevvana, M.; Gruene, T.; Kahle, B.; Zeeck, A.; Sheldrick, G.M. Structures of viscotoxins A1 and B from European mistletoe solved using native data alone. Acta Crystallogr. D Biol. Crystallogr. 2008, 64, 985–992. [Google Scholar] [CrossRef]
  47. Schaller, G.; Urech, K.; Giannattasio, M. Cytotoxicity of different viscotoxins and extracts from the European subspecies of Viscum album L. Phyther. Res. 1996, 10, 473–477. [Google Scholar] [CrossRef]
  48. Jaggy, C.; Musielski, H.; Urech, K.; Schaller, G. Quantitative determination of lectins in mistletoe preparations. Arzneim. Forsch./Drug Res. 1995, 45, 905–909. [Google Scholar]
  49. Urech, K.; Schaller, G.; Jäggy, C. Viscotoxins, mistletoe lectins and their isoforms in mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung 2011, 56, 428–434. [Google Scholar] [CrossRef] [PubMed]
  50. Majeed, M.; Rehman, R.U. Phytochemistry, Pharmacology, and Toxicity of an Epiphytic Medicinal Shrub Viscum album L. (White Berry Mistletoe). In Medicinal and Aromatic Plants; Aftab, T., Hakeem, K.R., Eds.; Springer: Cham, Switzerland, 2021; pp. 287–301. [Google Scholar]
  51. Zhang, R.-Z.; Zhao, J.-T.; Wang, W.-Q.; Fan, R.-H.; Rong, R.; Yu, Z.-G.; Zhang, Y.-L. Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities. J. Pharm. Anal. 2022, 12, 243–252. [Google Scholar] [CrossRef] [PubMed]
  52. Schaller, G.; Urech, K.; Grazi, G.; Giannattasio, M. Viscotoxin composition of the three European subspecies of Viscum album. Planta Med. 1998, 64, 677–678. [Google Scholar] [CrossRef]
  53. Beuth, J.; Stoffel, B.; Ko, H.L.; Jeljaszewiz, J.; Pulverer, G. Immunomodulating ability of galactoside-specific lectin standardized and depleted mistletoe extract. Arzneimittelforshung 1995, 45, 1240–1242. [Google Scholar]
  54. Segneanu, A.; Velciov, S.M.; Olariu, S.; Cziple, F.; Damian, D.; Grozescu, I. Bioactive molecules profile from natural compounds. In Amino Acid-New Insights and Roles in Plant and Animal; Asao, T., Asaduzzaman, M., Eds.; IntechOpen: Rijeka, Croatia, 2017. [Google Scholar]
  55. Wilson, H.A.; Huang, W.; Waldrip, J.B.; Judd, A.M.; Vernon, L.P.; Bell, J.D. Mechanisms by which thionin induces susceptibility of S49 cell membranes to extracellular phospholipase A2. Biochim Biophys Acta. 1997, 1349, 142–156. [Google Scholar] [CrossRef] [PubMed]
  56. Olnes, S.; Stirpe, F.; Sandvig, K.; Phil, A. Isolation and Characterization of Viscumin, a toxic lectin from Viscum album L. (mistletoe). J. Biol. Chem. 1982, 257, 13263–13270. [Google Scholar] [CrossRef]
  57. Bergmann, L.; Aamdal, S.; Marreaud, S.; Lacombe, D.; Herold, M.; Yamagichi, T.; Wilhelm-Ogunbiyi, K.; Lentzen, H.; Zwirzina, H. European Organisation for Research and Treatment of Cancer: Phase I trial of r viscumin (INN: Aviscumine) given subcutaneously in patients with advanced cancer: A study of the European Organisation for Research and Treatment of Cancer (EORTC protocol number 13001). Eur. J. Cancer 2008, 44, 1657–1662. [Google Scholar]
  58. Adler, M.; Langer, M.; Witthohn, K.; Eck, J.; Blohm, D.; Niemeyer, C.M. Detection of rViscumin in plasma samples by immunoPCR. Biochem. Biophys. Res. Commun. 2003, 300, 757–763. [Google Scholar] [CrossRef]
  59. Zwierzina, H.; Bergmann, L.; Fiebig, H.; Aamdal, S.; Schoffski, P.; Wittholm, K.; Lentzen, H. The preclinical and clinical activity of aviscumine: A potential anticancer drug. Eur. J. Cancer 2011, 47, 1450–1457. [Google Scholar] [CrossRef] [PubMed]
  60. Abuharbeid, S.; Apel, J.; Sander, M.; Fiedeler, B.; Langer, M.; Zuzarte, M. Cytotoxicity of the novel anti-cancer drug Viscumin depends on HER-2 levels in SKOV-3 cells. Biochem. Biophys. Res. Commun. 2004, 321, 403–412. [Google Scholar] [CrossRef] [PubMed]
  61. Niwa, H.; Tonevitsky, A.G.; Agapov, S.S.; Saward, S.; Pfuller, U.; Palmer, R.A. Crystal structure at 3 A of mistletoe lectin I, a dimeric type-II ribosome-inactivating protein, complexed with galactose. Eur. J. Biochem. 2003, 270, 2739–2749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Ahmad, M.S.; Rasheed, S.; Felke, S.; Khaliq, B.; Perbandt, M.; Choudhary, M.I.; Markiewick, W.T.; Barciszewski, J.; Betzel, C. Crystal Structure of Mistletoe Lectin I (ML-I) from Viscum album in Complex with 4-N-Furfurylcytosine at 2.85 Å Resolution. Med. Chem. 2018, 14, 754–763. [Google Scholar] [CrossRef] [PubMed]
  63. Krauspenhaar, R.; Eschenburg, S.; Perbandt, M.; Kaur, P.; Yadav, S.; Krauspenhaaar, R.; Beltzel, C.; Voelter, W.; Babu, C.R.; Singh, T.P. Crystal structure of mistletoe lectin I from Viscum album. Biochem. Biophys. Res. Commun. 1999, 257, 418–424. [Google Scholar] [CrossRef] [PubMed]
  64. Büssing, A.; Suzart, K.; Schweizer, K. Differences in the apoptosis-inducing properties of Viscum album L. extracts. Anti-Cancer Drugs 1997, 8 (Suppl. S1), S9–S14. [Google Scholar] [CrossRef]
  65. Vervecken, W.; Kleff, S.; Pfüller, U.; Büssing, A. Induction of apoptosis by mistletoe lectin I and its subunits. No evidence for cytotoxic effects caused by isolated A- and B-chains. Int. J. Biochem. Cell Biol. 2000, 32, 317–326. [Google Scholar] [CrossRef] [PubMed]
  66. Franz, H. Mistletoe lectins and their A and B chains. Oncology 1986, 43 (Suppl. S1), 23–34. [Google Scholar] [CrossRef]
  67. Franz, H. Mistletoe Lectins. In Advances in Lectin Research; Franz, H., Ed.; Springer: Berlin/Heidelberg, Germany, 1991; Chapter 2; pp. 33–50. [Google Scholar]
  68. Eugen, T.; Staub, D.; Graaff, M.; Wenlel, S. MicroProteins: Small size-big impact. Trends Plant Sci. 2015, 20, 477–482. [Google Scholar] [CrossRef]
  69. Bhate, K.K.; Dolde, V.; Wenkel, S. MicroProteins: Expanding functions and novel modes of regulation. Mol. Plant 2021, 14, 705–707. [Google Scholar] [CrossRef]
  70. Kushwaha, A.K.; Dwivedi, S.; Mukherejee, A.; Lingwan, M.; Dar, M.A.; Bhagavatula, L.; Datta, S. Plant microProteins. Small but powerful modulators of plant development. Science 2022, 25, 105400. [Google Scholar] [CrossRef] [PubMed]
  71. Zuber, D.; Widmer, A. Phylogeography and host race differentiation in the European mistletoe (Viscum album L.). Mol. Ecol. 2009, 18, 1946–1962. [Google Scholar] [CrossRef] [PubMed]
  72. Schrader-Fischer, G.; Apel, K. The Anticyclic Timing of Leaf Senescence in the Parasitic Plant Viscum album is Closely Correlated with the Selective Degradation of Sulfur-Rich Viscotoxins. Plant Physiol. 1993, 101, 745–749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Schroder, L.; Honyec, N.; Senkler, M.; Senkler, M.; Senkler, J.; Kuster, H.; Braun, H.-P. The gene space of European Mistetoe (Viscum album). Plant J. 2022, 109, 278–294. [Google Scholar] [CrossRef] [PubMed]
  74. Peñaloza, E.; Holandino, C.; Scherr, C.; de Araujo, P.I.P.; Borges, R.M.; Urech, K.; Baumgartner, S.; Garrett, R. Comprehensive metabolome analysis of fermented aqueous extracts of Viscum album L. by liquid chromatography−high resolution tandem mass spectrometry. Molecules 2020, 25, 4006. [Google Scholar] [CrossRef]
  75. Pietrzak, W.; Nowak, R.; Gawlik-Dziki, U.; Lemieszek, M.K.; Rzenski, W. LC-ESI-MS/MS identification of biologically active phenolic compounds in mistletoe berry extracts from different host trees. Molecules 2017, 22, 624. [Google Scholar] [CrossRef] [Green Version]
  76. Vanhaverbeke, C.; Jouboul, D.; Elie, N.; Prévost, M.; Meunier, C.; Michelland, S.; Cumin, V.; Ma, L.; Vermijlen, D.; Delporte, C.; et al. Untarget metabolomics approach to discriminate mistletoe commercial products. Sci. Rep. 2021, 111, 14205. [Google Scholar] [CrossRef] [PubMed]
  77. Zhang, R.-Z.; Zhao, J.-T.; Wang, W.-Q. Phenolic compounds in chilean mistletoe (quintral, Tristerix tetrandus) analyzed by UHPLC-Q/Orbitrap/MS/MS and its antioxidant properties. Molecules 2016, 21, 245. [Google Scholar]
  78. Luther, P.; Becker, H. Die Mistel. Botanik, Lektine, Medizinische Anwendung; Springer: Berlin/Heidelberg, Germany, 1987. [Google Scholar]
  79. Büssing, A. History of mistletoe uses. In Mistletoe. The Genus Viscum; Büssing, A., Ed.; Harwood Academic Publishers: Amsterdam, The Netherlands, 2000; pp. 1–6. [Google Scholar]
  80. Szurpnicka, A.; Kowalczuk, A.; Szterk, A. Biological activity of mistletoe: In vitro and in vivo studies and mechanisms of action. Arch. Pharm. Res. 2020, 43, 593–629. [Google Scholar] [CrossRef]
  81. Kleszken, E.; Timar, A.V.; Memete, A.R.; Miere, F.; Vicas, S.I. On overview of bioactive compounds, biological and pharmacological effects of mistletoe (Viscum album L.). Pharmacophore 2022, 13, 10–26. [Google Scholar] [CrossRef]
  82. Ahmed, S.; Mir, N.H.; Sultan, S.M. White berry mistletoe (Viscum album L.): A hemiparasitic plant: Occurrence and ethnobotanical use in Kashmir. J. Pharmacol. Phytochem. 2011, 7, 1831–1833. [Google Scholar]
  83. Bulut, G.; Haznederoglu, H.Z.; Dogan, A. An ethnobotanical study of medicinal plants in Acyoayam (Denizli-Turkey). J. Herb. Med. 2017, 10, 64–81. [Google Scholar] [CrossRef]
  84. Maruca, G.; Spampinato, G.; Turiano, D.; Laghetti, C.; Musarella, C.M. Ethnobotanical notes about medicinal and useful plants of the Reventino Massif tradition (Calabria region, Southern Italy). Genet. Resour. Crop Evol. 2019, 66, 1027–1040. [Google Scholar] [CrossRef]
  85. Senkardes, I.; Dogan, A.; Emre, G. An Ethnobotanical study of medicinal plants in Taşköprü (Kastamonu–Turkey). Front. Pharmacol. 2022, 13, 984065. [Google Scholar] [CrossRef]
  86. Zänker, K.S.; Kaveri, S.V. (Eds.) Mistletoe: From Mythology to Evidence-Based Medicine; Translational Research in Biomedicine; Karger: Basel, Switzerland, 2015; Volume 4, pp. 1–10. [Google Scholar]
  87. Aldhouse-Green, M. The moon and the mistletoe in search of ancient druids: Story of an ancient priest-hood. In Caesar’s Druids; Yale University Press: New Haven, CT, USA, 2010; Chapter 1; p. 19. [Google Scholar]
  88. Secondum, G.P. Naturalis Hystoria; Sillabe: Livorno, Italy, 2014; 16.248.1; ISBN 978888347739-3. [Google Scholar]
  89. Lindow, J. The tears of the Gods. A note on the death of Baidr in Scandinavian mythology. J. Engl. Ger. Philol. 2002, 101, 155–169. [Google Scholar]
  90. Azuma, J.; Kim, N.H.; Heux, L.; Vuong, R.; Chanzy, H. The cellulose system in viscin from mistletoe berries. Cellulose 2000, 7, 3–19. [Google Scholar] [CrossRef]
  91. Holbelt, H.; Fratzel, P.; Harrison, H.J. Mistletoe viscin: A hygro- and mechano-responsive cellulose-based adhesive for diverse material applications. PNAS Nexus 2022, 1, 1–11. [Google Scholar]
  92. Singh, B.N.; Saha, C.; Galun, D.; Upreti, D.K.; Bayry, J.; Kaveri, S.V. European Viscum album: A potent phytotherapeutic agent with multifarious phytochemicals, pharmacological properties and clinical evidence. RSC Adv. 2016, 6, 23837–23857. [Google Scholar] [CrossRef] [Green Version]
  93. Lev, E.; Ephraim, M.; Ben-Arye, E. European and Oriental mistletoe: From mythology to contemporary integrative cancer care. Eur. J. Integr. Med. 2011, 3, e133–e137. [Google Scholar] [CrossRef]
  94. Cicchetti, J.T. Viscum album—Magical Plant of Complexity and Paradox. Homoepatic Links 2005, 28, 118–122. [Google Scholar]
  95. Committee on Herbal Medicinal Products. Assessment Report on Viscum album L., Herba; Committee on Herbal Medicinal Product: London, UK, 2012. [Google Scholar]
  96. Kiele, G.; Albonico, H.-L.; Baars, E.; Hamre, H.J.; Zimmermann, P.; Kiene, H. Anthroposophic Medicine: An Integrative Medical System Originating in Europe. Glob. Adv. Health Med. 2013, 2, 20–31. [Google Scholar]
  97. Steiner, R.; Wegman, I. Grundlegendes für eine Erweiterung der Heilkunst nach Geisteswissenschaftlichen Erkenntnissen; Schattauer Verlag: Stuttgart, Germany; New York, NY, USA, 1991. [Google Scholar]
  98. Kienle, G.S.; Kiene, H.; Albonico, H.U. Anthroposophic Medicine: Effectiveness, Utility, Costs, Safety; Schattauer Verlag: Stuttgart, Germany; New York, NY, USA, 2006. [Google Scholar]
  99. Mengs, H.; Wittohn, K.; Scharzt, T. Value of mistletoe lectin standardized mistletoe extract for evaluating antitumor properties. Wien Med. Wochenschr. 1999, 149, 262–264. [Google Scholar] [PubMed]
  100. Scott, J.A.; Kearney, N.; Hummerston, S.; Molassiotis, A. Use of complementary and alternative medicine in patients with cancer: A UK survey. Eur. J. Oncol. Nurs. 2005, 9, 131–137. [Google Scholar] [CrossRef] [PubMed]
  101. Kienle, G.S.; Glockmann, A.; Schink, M.; Kiene, H. Viscum album L. extracts in breast and gynecological cancers: A systematic review of clinical and preclinical research. J. Exp. Clin. Cancer Res. 2009, 28, 79–85. [Google Scholar] [CrossRef] [Green Version]
  102. Horneber, M.A.; Bueschel, G.; Huber, R.; Linde, K.; Rostok, M. Mistletoe therapy in oncology. Cochrane Database Syst. Rev. 2008, 2, CD003297. [Google Scholar]
  103. Thronicke, A.; Steele, M.L.; Grah, C.; Hamre, H.J.; Zimmermann, P.; Kiene, H. Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer. BMC Complement. Altern. Med. 2017, 17, 534. [Google Scholar] [CrossRef] [Green Version]
  104. Schaefermeyer, G.; Schaefermeyer, H. Treatment of pancreatic cancer with Viscum album (Iscador): A retrospective study of 292 patients 1986–1996. Complement. Ther. Med. 1998, 6, 172–177. [Google Scholar] [CrossRef]
  105. Schnell-Inderst, P.; Steigenberger, C.; Mertz, M.; Otto, I.; Flatscher-Thöni, M.; Siebert, U. Additional treatment with mistletoe extracts for patients with breast cancer compared to conventional cancer therapy alone efficacy and safety, costs and cost-effectiveness, patients and social aspects, and ethical assessment. Ger. Med. Sci. 2022, 20, 10. [Google Scholar]
  106. Schötterl, S.; Miemietz, J.T.; Ilina, E.I.; Veninga, V.; Wirsik, N.-M.; Bernatz, S.; Lentzen, H.; Mittelbronn, M.; Naumann, U. Mistletoe-based drugs work in synergy with radio-chemotherapy in the treatment of glioma in vitro and in vivo in glioblastoma bearing mice. Evid. Based Complement. Altern. Med. 2019, 2019, 1376140. [Google Scholar] [CrossRef] [Green Version]
  107. Kienle, G.; Berrino, F.; Bussing, A.; Portalupi, E.; Rosenzweig, S.; Kiene, H. Mistletoe in cancer: A systematic review on controlled clinical trials. Eur. J. Med. Res. 2003, 8, 109–119. [Google Scholar]
  108. Reynel, M.; Villegas, Y.; Kiene, H. Intralesional and subcutaneous application of Viscum album L. (European mistletoe) extract in cervical carcinoma in situ: A CARE compliant case report. Medicine 2018, 97, e13420. [Google Scholar] [CrossRef] [PubMed]
  109. Oei, S.L.; Thronicke, A.; Kröz, M.; von Trott, P.; Shad, F.; Mathes, H. Impact of Oncological Therapy and Viscum album L. Treatment on Cancer-Related Fatigue and Internal Coherence in Nonmetastasized Breast Cancer Patients. Integr. Cancer Ther. 2020, 19, 1534735420917211. [Google Scholar] [CrossRef] [PubMed]
  110. Kienle, G.S.; Kiene, H. Complementary cancer therapy: A systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur. J. Med. Res. 2007, 12, 103–119. [Google Scholar] [PubMed]
  111. Valle, A.C.V.; Carvalho, A.C. Viscum album in Medicine Article Review. Int. J. Sci. Res. (IJSR) 2021, 10, 42–48. [Google Scholar]
  112. Freuding, M.; Keinki, C.; Kutschan, S.; Buentzel, J.; Huebner, J. Mistletoe in oncological treatment: A systematic review: Part 1 survival and safety and Part 2: Quality of life and toxicity of cancer treatment. J. Cancer Res. Clin. Oncol. 2019, 145, 695–707. [Google Scholar] [CrossRef]
  113. Ostermann, T.; Raak, C.; Büssing, A. Survival of cancer patients treated with mistletoe extract (Iscador): A systematic literature review. BMC Cancer 2009, 9, 451. [Google Scholar] [CrossRef] [Green Version]
  114. Goebell, P.J.; Otto, T.; Suhr, J.; Rubben, H. Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: A randomized phase II trial. J. Urol. 2002, 168, 72–75. [Google Scholar] [CrossRef]
  115. Cazacu, M.; Oniu, T.; Lungoci, C.; Mihailov, A.; Cipak, A.; Klinger, R.; Weiss, T.; Zarkovic, N. The influence of isorel on the advanced colorectal cancer. Cancer Biother. Radiopharm. 2003, 18, 27–34. [Google Scholar] [CrossRef]
  116. Piao, B.K.; Wang, Y.X.; Xie, G.R.; Mansmann, U.; Matthes, H.; Benth, J.; Lin, H.S. Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Res. 2004, 24, 303–309. [Google Scholar]
  117. Semiglazov, V.F.; Stepula, V.V.; Dudov, A.; Dudov, A.; Schnitker, J.; Mengs, U. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: A randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res. 2006, 26, 1519–1529. [Google Scholar]
  118. Kim, S.; Kim, K.C.; Lee, C. Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells. Phytomedicine 2017, 36, 183–193. [Google Scholar] [CrossRef] [PubMed]
  119. Kim, Y.; Kim, I.; Park, C.H.; Kim, J.B. Korean mistletoe lectin enhances natural killer cell cytotoxicity via upregulation of perforin expression. Asian Pac. J. Allergy Immunol. 2018, 36, 175–183. [Google Scholar] [CrossRef] [PubMed]
  120. Kleeberg, U.R.; Suciu, S.; Brocker, E.B.; Ruiter, D.J.; Chartier, C.; Lienard, D. Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness > 3 mm) or regional lymph node metastasis. Eur. J. Cancer 2004, 40, 390–402. [Google Scholar] [CrossRef] [PubMed]
  121. Klingbeil, M.G.; Xavier, F.C.A.; Sardinha, L.R.; Severino, P.; Mathor, M.; Rodriguez, R.V. Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines. Oncol. Rep. 2013, 30, 2316–2322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  122. Mazalovska, M.; Calvin Kouokam, J. Plant-derived lectins as potential cancer therapeutics and diagnostic tools. BioMed Res. Int. 2020, 2020, 1631394. [Google Scholar] [CrossRef]
  123. Park, R.; Kim, M.S.; So, H.S.; Meyer, C.F.; Keesler, G.; Zukowsky, M.; Tan, T.H.; Zao, Z. Activation of c-Jun N-terminal kinase 1 (JNK1) in mistletoe lectin II-induced apoptosis of human myeloleukemic U937 cells. Biochem. Pharm. 2000, 60, 1685–1691. [Google Scholar] [CrossRef]
  124. Park, W.B.; Lyu, S.Y.; Kim, J.H.; Chung, H.K.; Ahn, S.H.; Hong, S.Y.; Yoon, T.J.; Choi, M.J. Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis. Cancer Biother. Radiopharm. 2001, 16, 439–447. [Google Scholar] [CrossRef]
  125. Ernst, E.; Schmidt, K.; Steuer-Vogt, M.K. Mistletoe for cancer? A systematic review of randomised clinical trials. Int. J. Cancer 2003, 107, 262–267. [Google Scholar] [CrossRef]
  126. Evans, M.; Bryant, S.; Huntley, A.L.; Feder, G. Cancer patients’ experiences of using mistletoe (Viscum album): A qualitative systematic review and synthesis. Altern. Complement. Med. 2016, 22, 134–144. [Google Scholar] [CrossRef] [Green Version]
  127. Bar-Sela, G. White-Berry Mistletoe (Viscum album L.) as complementary treatment in cancer: Does it help? Eur. J. Integr. Med. 2011, 3, e55–e62. [Google Scholar] [CrossRef]
  128. Samtleben, R.; Hajto, T.; Hostanska, K.; Wagner, H. Mistletoe lectins as immunostimulants (chemistry, pharmacology and clinic). In Immunomodulatory Agents from Plants; Wagner, H., Ed.; Birkhauser Verlag: Basel, Switzerland, 1999; pp. 223–241. [Google Scholar]
  129. Jurin, M.; Zarković, N.; Hrzenjak, M.; Ilic, Z. Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. Oncology 1993, 50, 393–398. [Google Scholar] [CrossRef] [PubMed]
  130. Jurin, M.; Zarkovic, N.; Borovic, N.; Kissel, D. Viscum album L. preparation Isorel modifies the immune response in normal and cancer-bearing mice. Anticancer Drugs 1997, 8 (Suppl. S1), S27–S31. [Google Scholar] [CrossRef] [PubMed]
  131. Wrotek, S.; Skawiński, R.; Kozak, W. Postepy. Immunostimulatory properties of mistletoe extracts and their application in oncology. Postpy Hig. Med. Dosw. 2014, 68, 1216–1224. [Google Scholar] [CrossRef]
  132. Van Wely, M.; Stoss, M.; Gorter, R.W. Toxicity of a standardized mistletoe extract in immunocompromised and healthy individuals. Am. J. Ther. 1999, 6, 37–43. [Google Scholar] [CrossRef]
  133. Gardin, N.E. Immunological response to mistletoe (Viscum album L.) in cancer patients: A four-case series. Phytother. Res. 2009, 23, 407–411. [Google Scholar] [CrossRef] [PubMed]
  134. Elluru, S.R.; van Huyen, J.P.D.; Delignat, S.; Kazatchkine, M.D.; Friboulet, A.; Kaveri, S.V.; Bayri, J. Induction of maturation and activation of human dendritic cells: A mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer. BMC Cancer 2008, 8, 161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  135. Hedge, P.; Maddur, M.S.; Friboulet, A.; Bayry, J.; Kaveri, S.V. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2. PLoS ONE 2011, 6, e26312. [Google Scholar]
  136. Elleru, S.R.; Maddur, M.S.; Friboulet, A.; Bayry, J.; Kaveri, S.V. Dissecting the Anti-Inflammatory Effects of Viscum album: Inhibition of Cytokine-Induced Expression of Cyclo-Oxygenase-2 and Secretion of Prostaglandin E2. In Mistletoe: From Mythology to Evidence-Based Medicine; Translational Research in Biomedicine; Zänker, K.S., Kaveri, S.V., Eds.; Karger: Basel, Switzerland, 2015; Volume 4, pp. 67–73. [Google Scholar]
  137. Duong Van Huyen, J.P.; Delignat, D.; Bayry, J.; Kazatchkine, M.D.; Bruneval, P.; Nicoletti, A.; Kaveri, S.V. Interleukin-12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma. Cancer Lett. 2006, 243, 32–37. [Google Scholar] [CrossRef]
  138. Saha, C.; Hegde, P.; Friboulet, A.; Bayry, J.; Kaveri, S.V. Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA. PLoS ONE 2015, 10, e0114965. [Google Scholar] [CrossRef] [Green Version]
  139. Ha, S.-M.; Kim, J.-M.; Kim, J.-W. The potential Role of Korean Mistletoe as an Anti-inflammatory Suppletation. J. Immunol. Res. 2021, 2021, 2183427. [Google Scholar] [CrossRef]
  140. Bauer, R.; Becker, H.; Fintelmann, V.; Kemper, F.H.; Schilcher, H. (Eds.) Fortschritte in der Misteltherapie Aktueller Stand der Forschung und Klinischen Anwendung; KVC Verlag: Essen, Germany, 2005; pp. 543–554. [Google Scholar]
  141. Kim, B.K.; Choi, M.J.; Park, K.Y.; Cho, E.J. Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biol. Pharm. Bull. 2010, 33, 1152–1158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  142. Lavastre, V.; Cavelli, H.; Rathe, C.; Girard, D. Anti-inflammatory effect of Viscum album agglutinin-I (VAA-I): Induction of apoptosis in activated neutrophils and inhibition of lipopolysaccharide-induced neutrophilic inflammation in vivo. Clin. Exp. Immunol. 2004, 137, 272–278. [Google Scholar] [CrossRef]
  143. Vicaş, S.I.; Ruginǎ, D.; Socaciu, C. Comparative study about antioxidant activities of Viscum album from different host trees, harvested in different seasons. J. Med. Plants Res. 2011, 5, 2237–2244. [Google Scholar]
  144. Yesilada, E.; Deliorman, D.; Ergun, F.; Takaishi, Y.; Ono, Y. Effect of the Turkish subspecies of Viscum album on macrophage-derived cytokines. J. Ethnopharmacol. 1998, 61, 195–200. [Google Scholar] [CrossRef] [PubMed]
  145. Pieme, C.A.; Ngogang, J.; Costache, M. In vitro antiproliferative and anti-oxidant activities of methanol extracts of Urena lobata and Viscum album against breast cancer cell lines. Toxicol. Environ. Chem. 2012, 94, 987–999. [Google Scholar] [CrossRef]
  146. Sárpataki, O.; Sevastre, B.; Stan, R.; Olah, N.K.; Hanganu, D.; Bedeceu, I.; Ionescu, C.; Marcus, I. Viscum album, L. Influence on the Antioxidant Enzymes Activity in Ehrlich Tumor Cells In Vivo. Bull. Univ. Agric. Sci. Vet. Med. Cluj-Napoca—Vet. Med. 2014, 71, 198–203. [Google Scholar]
  147. Holandino, C.; Melo, M.N.; Oliveira, A.P.; da Costa Batista, J.V.; Capella, M.A.M.; Garrett, R.; Grazi, M.; Ramm, H.; Dalla Torre, C.; Schaller, G.; et al. Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts. BMC Complement. Med. Ther. 2020, 20, 215. [Google Scholar] [CrossRef]
  148. Yousefvand, S.Y.; Fathahi, F.; Hosseini, S.M.; Urech, K.; Schaller, G. Viscotoxin and lectin content in foliage and fruits of Viscum album L. on the main host trees of Hycanian forests. Sci. Rep. 2002, 12, 10383. [Google Scholar] [CrossRef]
  149. Pietrzak, W.; Nowak, R.; Olech, M. Effect of extraction method on phenolic content and antioxidant activity of mistletoe extracts from Viscum album subsp. abietis. Chem. Pap. 2014, 68, 976–982. [Google Scholar] [CrossRef]
  150. Papuc, C.; Crivineanu, M.; Goran, G.; Nicorescu, V.; Durdun, N. Free Radicals Scavenging and Antioxidant Activity of European Mistletoe (Viscum album) and European Birthwort (Aristolochia clematitis). Rev. Chim. 2010, 61, 619–622. [Google Scholar]
  151. Speisky, H.; Shahidi, F.; de Camargo, A.C.; Fuentes, J. Revisiting the Oxidation of Flavonoids: Loss, Conservation and Enhancement of Their Antioxidant Properties. Antioxidant 2022, 91, 133. [Google Scholar] [CrossRef]
  152. Dai, J.K.; Cao, D.; Li, C.-H. Three new bioactive flavonoids glycosides from Viscum album. Chin. J. Nat. Med. 2019, 17, 545–550. [Google Scholar] [CrossRef]
  153. Orhan, D.D.; Calis, I.; Ergun, F. Two New Flavonoid Glycosides from Viscum album spp. album. Pharm. Biol. 2002, 40, 380–383. [Google Scholar] [CrossRef]
  154. Oremosu, A.; Edem, E.E.; Dosumu, O.O.; Osuntoki, A.A. African mistletoe (Loranthaceae) ameliorates cholesterol-induced motor deficit and oxidative stress in adult BALB/c mice. J. Exp. Clin. Anat. 2017, 16, 121–131. [Google Scholar]
  155. Orhan, D.D.; Aslan, M.; Sendogdu, N.; Ergun, F.; Yesilada, E. Evaluation of the hypoglycemic effect and antioxidant activity of three Viscum album subspecies (European mistletoe) in streptozotocin-diabetic rats. J. Ethnopharmacol. 2005, 98, 95–102. [Google Scholar] [CrossRef] [PubMed]
  156. Shahaboddin, M.E.; Pouramir, M.; Moghadamnia, A.A. Antihyperglycemic and antioxidant activity of Viscum album extract. Afr. J. Pharm. Pharm. 2011, 5, 432–436. [Google Scholar] [CrossRef]
  157. Elsasser-Beile, U.; Voss, M.; Schule, R.; Wetterauer, U. Biological effects of natural and recombinant mistletoe lectin and an aqueous mistletoe extract on human monocytes and lymphocytes in vitro. J. Clin. Lab. Anal. 2000, 14, 255–259. [Google Scholar] [CrossRef]
  158. Orhan, D.D.; Senol, F.S.; Hosbas, S.; Orhan, I.E. Assessment of cholinesterase and tyrosinase inhibitory and antioxidant properties of Viscum album L. samples collected from different host plants and its two principal substances. Ind. Crops Prod. 2014, 62, 341–349. [Google Scholar] [CrossRef]
  159. Sengul, M.; Yildiz, H.; Gungor, N.; Cetin, B.; Eser, Z.; Ercisli, S. Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak. J. Pharm. Sci. 2009, 22, 102–106. [Google Scholar] [PubMed]
  160. Delebinski, C.I.; Twardziok, M.; Kleinsimon, S.; Hoff, F.; Mulson, K.; Roff, J.; Jager, S.; Eggert, A.; Seifer, G. A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo. PLoS ONE 2015, 10, e0133892. [Google Scholar] [CrossRef]
  161. Kauczor, G.; Delebinski, C.; Jäger, S.; Seeger, K.; Seifert, G. Triterpene acid containing Viscum album L. extracts mediate apoptosis in paediatric solid cancer cells. BMC Complement. Altern. Med. 2012, 12, P18. [Google Scholar] [CrossRef] [Green Version]
  162. Delebinski, C.I.; Jaeger, S.; Kemnitz-assanim, K.; Henze, G.; Lode, H.N.; Seifert, G.J. A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Cell Prolif. 2012, 45, 176–181. [Google Scholar] [CrossRef]
  163. Kleinsimon, S.; Longmuss, E.; Rolff, J.; Jager, S.; Debelinski, C.; Seifert, G. GADD45A and CDKN1A Are Involved in Apoptosis and Cell Cycle Modulatory Effects of Viscum TT with Further Inactivation of the STAT3 Pathway. Sci. Rep. 2018, 8, 5750. [Google Scholar] [CrossRef] [Green Version]
  164. Nhiem, N.X.; Kiem, P.V.; Minh, C.V.; Kim, N.; Park, S.; Lee, H.Y.; Kim, E.S.; Kim, Y.H.; Kim, S.; Koh, Y.-S.; et al. Diarylheptanoids and flavonoids from Viscum album inhibit LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. J. Nat. Prod. 2013, 76, 495–502. [Google Scholar] [CrossRef] [PubMed]
  165. Kim, S.Y.; Yang, E.J.; Son, Y.K.; Yeo, J.-H.; Song, K.-S. Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol. Food Funct. 2016, 7, 2270–2277. [Google Scholar] [CrossRef]
  166. Panossian, A.; Kocharian, A.; Matinian, K.; Yeo, J.-H.; Song, K.-S. Pharmacological activity of phenylpropanoids of the mistletoe, Viscum album L., host: Pyrus caucasica fed. Phytomedicine 1998, 5, 11–17. [Google Scholar] [CrossRef] [PubMed]
  167. Kleszken, E.; Purcarea, C.; Pallag, A.; Rnaga, F.; Memete, A.R.; Miere, F.; Vicas, S.I. Phytochemical Profile and Antioxidant Capacity of Viscum album L. subsp. album and Effects on Its Host Trees. Plants 2022, 11, 3021. [Google Scholar] [CrossRef] [PubMed]
  168. Billman, G.E. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front. Physiol. 2020, 11, 200. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  169. Modell, H.; Cliff, W.; Michael, J.; McFarland, J.; Wenderoth, M.P.; Wrigt, A. A physiologist’s view of homeostasis. Adv. Physiol. Educ. 2015, 39, 259–266. [Google Scholar] [CrossRef] [Green Version]
  170. Amer, B.; Johan Juvik, O.-L.; Francis, G.W.; Fossen, T. Novel GHB-derived natural products from European mistletoe (Viscum album). Pharm. Biol. 2013, 51, 981–986. [Google Scholar] [CrossRef]
  171. Hostanska, K.; Hajto, T.; Fischer, J.; Mengs, U.; Weber, K.; Lentzen, H.; Seller, R. Selective modulation of phosphatidylserine exposure on subpopulations of human peripheral blood lymphocytes by a plant lectin, Viscum album agglutinin (VAA)-I and its recombinant form (rVAA) in vitro. Cancer Detect. Prev. 1999, 23, 511–523. [Google Scholar] [CrossRef] [PubMed]
  172. Yusuf, L.; Oladunmoye, M.K.; Ogundare, A.O. In-vivo antibacterial activities of mistletoe (Viscum album) leaves extract growing on cocoa tree in Akure North, Nigeria. Eur. J. Biotechnol. Biosci. 2013, 1, 37–42. [Google Scholar]
  173. Crimeen-Irwin, B.; Scalzo, K.; Gloster, S.; Mottram, P.L.; Plebanski, M. Failure of immune homeostasis—The consequences of under and over reactivity. Curr. Drug Targets Immune Endocr. Metab. Disord. 2005, 5, 413–422. [Google Scholar] [CrossRef]
  174. Scrivo, R.; Vasile, M.; Bartosiewicz, I.; Valesini, G. Inflammation as “common soil” of the multifactorial diseases. Autoimmun. Rev. 2011, 10, 369–374. [Google Scholar] [CrossRef]
  175. Deliorman, D.; Ergun, F.; Sener, B.; Palittapongarnpim, P. Evaluation of antimycobacterial activity of Viscum album subspecies. Pharm. Biol. 2001, 39, 381–383. [Google Scholar] [CrossRef]
  176. Hussain, M.A.; Khan, M.Q.; Hussain, N.; Habib, T. Antibacterial and antifungal potential of leaves and twigs of Viscum album L. J. Med. Plants Res. 2011, 5, 5545–5549. [Google Scholar]
  177. Kenar, N.; Erdonmez, D.; Turkmen, K.E. Anti-quorum sensing and anti-biofilm activity of Viscum album L. on different pathogenic bacteria. J. Biotechnol. 2016, 1000, 1000. [Google Scholar] [CrossRef]
  178. Oguntoye, S.O.; Olatunji, G.A.; Kolawole, O.M.; Enonbun, K.I. Phytochemical screening and antibacterial activity of Viscum album (mistletoe) extracts. Plant Sci. Res. 2008, 1, 44–46. [Google Scholar]
  179. Erturk, Ö.; Kati, H.; Yayli, N.; Demirbag, Z. Antimicrobial activity of Viscum album L. subsp. abietis (Wiesb). Turk. J. Biol. 2003, 27, 255–258. [Google Scholar]
  180. Kusi, M.; Shrestha, K.; Malla, R. Study on phytochemical, antibacterial, antioxidant and toxicity profile of Viscum album Linn associated with Acacia catechu. Nepal J. Biotechnol. 2015, 3, 60–65. [Google Scholar] [CrossRef] [Green Version]
  181. Turker, A.U.; Yildirim, A.B.; Karakas, F.P. Antitumor and antibacterial activities of Viscum album L. grown on different host trees. Spat DD 2012, 2, 229–236. [Google Scholar] [CrossRef] [Green Version]
  182. WHO. New release. SEARO. 4 February 2022. New Delhi. See also Ferlay, J.; Ervik, M.; Lam, F.; Colombet, M.; Mery, L.; Piñeros, M. et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020. Available online: (accessed on 28 February 2021).
  183. Song, K.S.; Yoon, D.K.; Bum, K.J. Chemical Pleurodesis Using Doxycycline and Viscum album extract. J. Chest Surg. 2017, 50, 2765–2786. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  184. Lu, H.; Ouyang, W.; Huang, C. Inflammation, a Key Event in Cancer Development. Mol. Cancer Res. 2006, 4, 221–233. [Google Scholar] [CrossRef] [Green Version]
  185. Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther. 2021, 6, 263. [Google Scholar] [CrossRef]
  186. Philip, M.; Rowley, D.A.; Schreiber, H. Inflammation as a tumor promoter in cancer induction. Semin. Cancer Biol. 2004, 14, 433. [Google Scholar] [CrossRef]
  187. Okada, F. Inflammation and free radicals in tumor development and progression. Redox Rep. 2002, 7, 357. [Google Scholar] [CrossRef]
  188. Balkwill, F.; Mantovani, A. Inflammation and cancer: Back to Virchow? Lancet 2001, 357, 539. [Google Scholar] [CrossRef] [PubMed]
  189. Nathan, C. Points of control in inflammation. Nature 2002, 420, 846–852. [Google Scholar] [CrossRef]
  190. Khusmurrokhma, G.; Wati, F.F. Tumor-promoting inflammation in lung cancer: A literature review. Ann. Med. Surg. 2022, 79, 104022. [Google Scholar]
  191. Multhoff, G.; Molls, M.; Randons, J. Chronic Inflammation in Cancer Development. Front. Immunol. 2012, 2, 98. [Google Scholar] [CrossRef] [Green Version]
  192. Alam, M.M.; Rahman, T.; Afroz, Z.; Chakraborty, P.A.; Wahab, A.; Zaman, S.; Hawlader, M.D.H. Quality of Life (QoL) of cancer patients and its association with nutritional and performance status: A pilot study. Heliyon 2020, 6, e05250. [Google Scholar] [CrossRef]
  193. Yang, C.R.; Hsieh, S.L.; Ho, F.M.; Lin, W.W. Decoy receptor 3 increases monocyte adhesion to endothelial cells via NF-nB-dependent up-regulation of intercellular adhesion molecule-1, VCAM-1, and IL-8 expression. J. Immunol. 2005, 174, 1647. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  194. Tabiasco, J.; Pont, F.; Fournié, J.-J.; Vercellone, A. Mistletoe viscotoxins increase natural killer cell mediated cytotoxicity. Eur. J. Biochem. 2002, 269, 2591–2600. [Google Scholar] [CrossRef] [PubMed]
  195. Zalba, S.; ten Hagen, T.L.M. Cell membrane modulation as adjuvant in cancer therapy. Cancer Treat. Rev. 2017, 52, 48–57. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  196. Escriba, P.V. Membrane-lipid therapy: A new approach on molecular medicine. Trends Mol. Med. 2006, 12, 34–35. [Google Scholar] [CrossRef] [PubMed]
  197. Chromanska, A.; Chwilkowska, A.; Kulbaka, J.; Baczynska, D.; Rembialkowska, N.; Szewczyk, A.; Michel, O.; Gajewska-Naryniecka, A.; Przystupski, D.; Saczko, J. Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy. Molecules 2021, 26, 1850. [Google Scholar] [CrossRef]
  198. Maier, G.; Fiebig, H.H. Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro. Anticancer Drugs 2002, 13, 373–379. [Google Scholar] [CrossRef]
  199. Melzer, J.; Iten, F.; Hostanska, K.; Saller, R. Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forsch Komplementmed. 2009, 16, 217–226. [Google Scholar]
  200. Ribéreau-Gayon, G.; Jung, M.L.; Baudino, S.; Sallé, G.; Beck, J.P. Effects of mistletoe (Viscum album L.) extracts on cultured tumor cells. Experientia 1986, 42, 594–599. [Google Scholar] [CrossRef]
  201. Chai, Y.; Zhao, M. ITRAQ-Based Quantitative Proteomic Analysis of the Inhibitory Effects of Polysaccharides from Viscum coloratum (Kom.) Nakai on HepG2 Cells. Sci. Rep. 2017, 4, 4596. [Google Scholar]
  202. Vergara-Barberàn, M.; Lerma-Garcìa, M.; Nicoletti, M.; Simò-Alfonso, E.F.; Herero-Martinez, J.M.; Fasoli, E.; Rigetti, P.G. Proteomic fingerprint of mistletoe (Viscum album L.) via recombinatorial peptide ligand libraries and mass spectrometry analysis. J. Proteom. 2017, 164, 52–58. [Google Scholar] [CrossRef]
  203. Tsekouras, V.; Mavrikon, M.; Vlachakis, D.; Makridakis, M.; Stroggilos, R.; Zoidakis, J.; Termentzi, A.; Moschopouou, G.; Kintzios, S. Proteome analysis of leaf, stem and callus in Viscum album and identification of lectins and viscotoxins with bioactive properties. Plant Cell Tissue Organ Cult. 2020, 141, 167–178. [Google Scholar] [CrossRef]
  204. Zarković, T.; Kalisnik, I.; Loncarić, S.; Borovic, S.; Mang, S.; Kissel, D.; Konitzer, M.; Jurin, M.; Grainza, S. Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10. Cancer Biother. Radiopharm 1998, 13, 121–131. [Google Scholar] [CrossRef] [PubMed]
  205. Melo, M.N.d.O.; Ochioni, A.C.; Zancan, P.; Oliveira, A.P.; Grazi, M.; Garrett, R.; Holandino, C.; Baumgartner, S. Viscum album mother tinctures: Harvest conditions and host trees influence the plant metabolome and the glycolytic pathway of breast cancer cells. Front. Pharmacol. 2022, 13, 1027931. [Google Scholar] [CrossRef]
  206. Zarkovic, N. Adjuvant Cancer Biotherapy by Viscum album Extract Isorel: Overview of Evidence Based Medicine Findings. Coll. Antropol. 2005, 39, 701–708. [Google Scholar]
  207. Dairo, G.; Ilesanmi, A.; Balogun, T.; Ward, M.; Soendergaard, M.; Determan, J. Computational Evaluation of Bioactive Compounds from Viscum album (mistletoe) as inhibitors of 63 for Pancreatic Cancer treatment. In Biological and Medicinal Chemistry; ChemRXiV; Cambridge Open Engage: Cambridge, UK, 2022. [Google Scholar]
  208. Coulon, A.; Berkane, E.-B.; Sautereau, A.H.; Urech, K.; Rouge, P.; Lopez, A. Mode of membrane interaction of natural cysteine-rich peptide: Viscotoxin A3. Biochim. Biophys. Acta 2002, 1559, 145–158. [Google Scholar] [CrossRef] [Green Version]
  209. Coulon, A.; Mosbah, A.; Lopez, A.; Sautereau, A.-M.; Schaller, G.; Urech, K.; Rangé, P.; Darbon, H. Comparative membrane interaction study of viscotoxins A3, A2, and B from mistletoe (Viscum album) and connection with their structures. Biochem. J. 2003, 374, 71–78. [Google Scholar] [CrossRef]
  210. Baek, J.-H.; Jeon, Y.; Han, K.-W.; Jung, D.H.; Kim, K.O. Effect of mistletoe extract on tumor response in neoadjuvant chemotherapy for rectal cancer: A cohort study. World J. Surg. Oncol. 2021, 19, 18. [Google Scholar] [CrossRef]
  211. Choi, H.J.; Park, S.; Choi, Y.N.; Kim, S.-D.; Kwag, E.-B.; Song, S.-Y.; Park, J.H.; Kim, J.K.; Seo, C.; Choi, J.J.; et al. Selective Immune Modulating Activities of Viscum album and Its Components; A Possibility of Therapeutics on Skin Rash Induced by EGFR Inhibitors. Integr. Cancer Ther. 2022, 21, 15347354221118332. [Google Scholar] [CrossRef]
  212. Bocci, V. Mistletoe (Viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. J. Biol. Regul. Homeost. Agents 1993, 7, 1–6. [Google Scholar]
  213. Braedel-Ruoff, S. Immunomodulatory effects of Viscum album extracts on natural killer cells: Review of clinical trials. Complement. Med. Res. 2010, 17, 63–73. [Google Scholar] [CrossRef] [PubMed]
  214. Chernyshov, V.P.; Omelchenko, L.I.; Heusser, P.; Chernyshova, L.I.; Vodyanik, M.A.; Vykhovanets, E.V.; Galazyk, L.V.; Pochinov, T.V.; Goviday, N.V.; Gumenyuk, K.; et al. Immunomodulatory actions of Viscum album (Iscador) in children with recurrent respiratory disease as a result of the Chernobyl nuclear accident. Complement. Ther. Med. 1997, 5, 141–146. [Google Scholar] [CrossRef]
  215. Stan, R.L.; Hangan, A.C.; Dican, L.; Sevastre, B.; Hanganu, D.; Catoi, C.; Sarpataki, O.; Ionescu, C.M. Comparative study concerning mistletoe viscotoxins antitumor activity. Acta Biol. Hung. 2013, 64, 279–288. [Google Scholar] [CrossRef]
  216. Rocha, M.S.; Batista, J.V.C.; Melo, M.N.O.; de Campos, V.E.B.; Toledo, A.L.M.M.; Oliveira, A.P.; Picciani, P.M.; Baumgartner, S.; Holandino, C. Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity. Farmaceutica 2022, 14, 27. [Google Scholar]
  217. Zuzak, T.J.; Wasmuth, A.; Bernitzki, S.; Schwermer, M.; Laugher, A. Safety of high-dose intravenous mistletoe therapy in pediatric cancer patients: A case series. Complement. Ther. Med. 2018, 40, 198–202. [Google Scholar] [CrossRef] [PubMed]
  218. Kienle, S.G.; Grungel, R.; Keine, H. Safety of higher-dosage of Viscum album L. in animals and humans—Systematic review of immune changes and safety parameters. BMC Complement. Altern. Med. 2011, 11, 72. [Google Scholar] [CrossRef] [Green Version]
  219. Schad, F.; Thronicke, A. Safety of Combined Targeted and Helixor® Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study. Int. J. Environ. Res. Public Health 2023, 20, 2565. [Google Scholar] [CrossRef]
  220. Grossarth-Maticek, R.; Kiene, H.; Baumgartner, S.M.; Ziegler, R. Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: Prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern. Ther. Health Med. 2001, 7, 57–66. [Google Scholar]
  221. Ostermann, T.; Appelbaum, S.; Poier, D.; Boehm, K.; Raak, C.; Bussing, A. A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings. Complement. Med. Res. 2020, 27, 260–271. [Google Scholar] [CrossRef]
  222. Matthes, H.; Friedel, W.E.; Bock, P.-R.; Zancher, K.S. Molecular Mistletoe Therapy: Friend or Foe in Established Anti-Tumor Protocols? A Multicenter, Controlled, Retrospective Pharmaco-Epidemiological Study in Pancreas Cancer. Curr. Mol. Med. 2010, 10, 434–439. [Google Scholar] [CrossRef] [Green Version]
  223. Enesel, M.B.; Acalovschi, I.; Grosu, V.; Sbarcea, A.; Rusu, C.; Dobre, A.; Weiss, T.; Zarkovic, W. Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients. Anticancer Res. 2005, 25, 4583–4590. [Google Scholar] [PubMed]
  224. Anonimous. A Prospective Dose Finding Study of Iscador Infusion; HaEmek Medical Center: Afula, Israel, 2020. [Google Scholar]
  225. Wode, K.; Nordberg, J.H.; Kienle, G.; Elander, N.O.; Bernharsoon, B.-M.; Sunde, B.; Sharp, L.; Henriksson, R.; Fransson, P. Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: Study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL). Trial 2020, 21, 783. [Google Scholar] [CrossRef] [PubMed]
  226. Schad, F.; Thronicke, A.; Steele, M.L.; Merkle, A.; Matthes, B.; Grah, C.; Matthes, H. Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis. PLoS ONE 2018, 13, e0203058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  227. Thronicke, A.; Schad, F.; Debus, M.; Graboski, J.; Soldner, G. Viscum album L.-Therapy in Oncology: An Update of Current Evidence. Complement. Med. Res. 2022, 29, 362–368. [Google Scholar] [CrossRef]
  228. Bryant, S.; Dubcan, L.; Feder, G.; Huntley, A. A pilot study of the mistletoe and breast cancer (MAB) trial: A protocol for a randomised double-blind controlled trial. Pilot Feasibility Stud. 2022, 8, 78. [Google Scholar] [CrossRef]
  229. Steele, M.; Axtner, J.; Happe, A.; Kroz, M.; Matthes, H.; Schad, F. Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L.) Preparation on Oncology. Integr. Cancer Ther. 2014, 14, 140–148. [Google Scholar] [CrossRef]
  230. Zarkovic, N.; Vukovic, T.; Loncaric, I.; Zarkovic, S.; Borovic, S.; Cipak, A.; Sabolovic, S.; Konitzer, M.; Morig, S. An Overview on Anticancer Activities of the Viscum Album Extract Isorel®. Cancer Biother. Radiopharm. 2001, 16, 55–62. [Google Scholar]
  231. Lee, Y.-G.; Jung, I.; Koo, D.-H.; Kang, D.-Y.; Oh, T.Y.; Oh, S.; Lee, S.-S. Efficacy and safety of Viscum album extract (Helixor-M) to treat malignant pleural effusion in patients with lung cancer. Support Care Cancer 2019, 27, 1945–1949. [Google Scholar] [CrossRef]
  232. Kim, C.-W.; Kim, J.-S.; Lee, A.-H.; Kim, Y.-S. Viscum album extract (Helixor-M) treatment for thoracic duct injury after modified radical neck dissection: A case report. Gland Surg. 2021, 10, 832–836. [Google Scholar] [CrossRef]
  233. Rostok, M. Mistletoe in the treatment of cancer. Bundesgesundheitsblatt Gesundh. Gesundh. 2020, 63, 535–540. [Google Scholar]
  234. Staupe, H.; Buentzel, J.; Keinki, C.; Buentzel, J.; Haiebner, J. Systematic analysis of mistletoe prescriptions in clinical studies. J. Cancer Res. Clin. Oncol. 2022. [Google Scholar] [CrossRef] [PubMed]
  235. Young, J.P.; Sang, K.M.; Jang, Y.K.; Yun, S.S.; Park, S.C. Retroperitoneal Viscum album extract instillation in patients with a large amount of drainage after kidney transplantation. Ann. Surg. Treat. Res. 2021, 101, 368–373. [Google Scholar]
  236. Kelter, G.; Jorg, M.; Schierholz, H.; Fiebig, H.H. Cytotoxic Activity and Absence of Tumor Growth Stimulation of Standardized Mistletoe Extracts in Human Tumor Models In Vitro. Anticancer Res. 2007, 27, 223–234. [Google Scholar] [PubMed]
  237. Fellmer, K.E. A clinical trial of Iscador: Follow-up treatment of irradiated genital carcinomata for the prevention of recurrences. Br. Homeopat. J. 1968, 57, 43–47. [Google Scholar] [CrossRef]
  238. Montero, G.D.; Valladares, M.B.; Tornes, C. Tratamiento homeopático y convencional de la hipertensión arterial. Rev. Méd. Homeopat. 2016, 9, 53–58. [Google Scholar] [CrossRef]
  239. Oberbaum, M.; Yaniv, I.; Ben-Gal, Y.; Stein, J.; Ben-Zvi, N.; Frredman, L.S.; Branski, D. A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation. Cancer 2001, 92, 684–690. [Google Scholar] [CrossRef]
  240. Bonamin, L.; Cardoso, T.N.; Carvalho, A.C.; Amaral, J. A systematic review about animal models in homeopathic research: The last five years of PubMed indexed papers. Int. J. High Dilution Res. 2015, 14, 45. [Google Scholar] [CrossRef]
  241. Christen-Clottu, O.; Klocke, P.; Burger, D.; Straub, R.; Gerber, V. Treatment of clinically diagnosed equine. J. Vet. Intern. Med. 2010, 24, 1483–1489. [Google Scholar] [CrossRef]
  242. Carvalho, A.; Valle, A.C.V. Treatment of Alimentary Lymphoma in Cat (Felis catus) by Injectable Homeopathy—Case Report. Integr. J. Vet. Biosc. 2021, 5, 19. [Google Scholar]
  243. Carvalho, A.C.; Porto, E.; Bonamin, L. Canine neurofibrosarcoma treatment with Viscum album in serial dilutions. Homeopathy 2013, 12, 106. [Google Scholar]
  244. Valle, A.C.V.; de Carvalho, A.C. Viscum album in Veterinary Medicine. IJSR 2021, 10, 42–49. [Google Scholar]
  245. Lopes, D.F.; Valle, A.C.V.; Sibata, M.N. Treatment and staging of canine lymphoma with ultra-diluted Viscum album and homeopathic associations: Case report. Rev. Educ. Contin. Med. Vet. Zootecn. CRMV-SP 2018, 16, 89–90. [Google Scholar]
  246. Graf, R.; Gruntzig, K.; Boo, G.; Hassig, R.; Axhauser, K.W.; Fabrikant, S.; Welle, M.; Meier, D.; Guscett, F.; Folkers, G.; et al. Swiss feline cancer registry 1965–2008: The influence of sex, breed and age on tumour types and tumour locations. J. Comp. Pathol. 2016, 154, 195–210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  247. Bonamin, L.V.; Carvalho, A.; Waisse, S. Viscum album (L.) in experimental animal tumours: A meta-analysis. Exp. Ther. Med. 2017, 13, 2723–2740. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  248. Biegel, U.; von Bodungen, U.; Ruess, K.; Reif, M.; Knauf, Y.; Stratmann, N. Mistletoe in adjuvant cancer treatment of companion animals. Planta Med. 2019, 85, 1392. [Google Scholar]
  249. Biegel, U.; Ruess-Melzer, K.; Klocke, P. Orally administered Viscum album Quercus dilutions in the therapy of feline fibrosarcoma in cats. Phytomedicine 2011, 18, 24. [Google Scholar] [CrossRef]
  250. Valle, A.C.V.; Andrade, R.V.; Sibata, M.N.; Carvalho, A.C. Ultradiluted Viscum album in the Treatment of Melanoma in a Dog (Canis familiaris)—Case Report. Homeopathy 2020, 109, 1–18. [Google Scholar]
  251. Valle, A.C.V.; Sibata, M.N.; Andrade, R.V.; Carvalho, A.C. Homeopathy for the Treatment of Transmissible Venereal Tumor (TVT) in a Mixed-Breed Female Dog. Adv. Complement. Altern. Med. 2019, 5, 422–424. [Google Scholar]
  252. Wright, A.; Watanabe, R.; Koehler, J.W. European Mistletoe (Viscum album) Extract Is Cytotoxic to Canine High-Grade Astrocytoma Cells In Vitro and Has Additive Effects with Mebendazole. Vet. Sci. 2022, 9, 31. [Google Scholar] [CrossRef]
  253. Heidner, G.L.; Kornegay, J.N.; Page, R.L.; Dodge, R.K.; Thrall, D.E. Analysis of survival in a retrospective study of 86 dogs with brain tumors. J. Vet. Intern. Med. 1991, 5, 219–226. [Google Scholar] [CrossRef]
  254. Hawu, O.; Ravhuhali, K.E.; Musekwa, M.G.; Sipango, N.; Mudau, H.S.; Mokoboki, K.H.; Moyo, B. Utilization of the Viscum Species for Diet and Medicinal Purposes in Ruminants: A Review. Animals 2022, 12, 2569. [Google Scholar] [CrossRef] [PubMed]
  255. Blostin, R.; Faivre, C. Bénéfices du gui fermenté chez le chat après exérèse de fibrosarcome: Résultats d’une étude préliminaire. Phytotherapie 2008, 6, 352–358. [Google Scholar] [CrossRef]
  256. Roy, S. Pharmacokinetics of homeopathis mother tincture Viscum album after intradermal administration. Clin. Exp. Homeopath. 2019, 6, 20–222. [Google Scholar]
  257. Valle, A.C.V.; Aguiar, L.R.; Brunel, H.S.S.; Malard, P.F.; Andrade, R.V.; Villaroel, C.L.P.; Andrade, R.V. Homeopathic Viscum album (10-3) is more cytotoxic in vitro Culture of Human Breast Cancer Cell Line to Human Mesenchymal Stem Cell. Int. J. High Dilution Res. 2020, 19, 25–34. [Google Scholar] [CrossRef]
  258. Valle, A.C.V.; Brunel, H.S.S.; Malard, P.F.; Villaroel, C.L.; Andrade, R.V. Homeopathic Viscum album at Potencies D3 and 200CH Presents Cytokine Modulatory Effect Produced by in vitro Culture of Mesenchymal Stem Cells. Curr. Res. Complement. Altern. Med. 2022, 6, 155. [Google Scholar]
  259. Valle, A.C.V.; Aguiar, R.L.; Brunel, H.S.S.; Malard, P.F.; Andrade, R.V. Osteosarcoma cells are inhibited by homoeopathic Viscum album. J. Integr. Stand. Homoeopath. 2020, 3, 59–63. [Google Scholar] [CrossRef]
  260. Hollandino, C.; Melo, M.; da Costa Batista, I.; da Valga, F.; da Costa Batista, J.V.; Capella, M.A.M.; Garrett, R.; Grazi, M.; Weissenstein, U.; Baumgartner, S. Viscum album homeopathic tinctures: Phytochemical Profile and Antiproliferative Activity. Int. J. High Dilution Res. 2018, 17, 4–8. [Google Scholar]
  261. Karagoz, A.; Onay, E.; Arda, N.; Kuru, A. Antiviral potency of mistletoe (Viscum album ssp. album) extracts against human parainfluenza Virus type 2 in Vero cells. Phytother. Res. 2003, 17, 560–562. [Google Scholar] [CrossRef]
  262. Valle, A.C.V.; Carvalho, A.C. Ultra-diluted Viscum album in the treatment of cutaneous melanoma in a dog (Canis familiaris). Case report. Paripex Indian J. Res. 2021, 10, 1–4. [Google Scholar]
  263. Mellor D: Mistletoe in homoeopathic cancer treatment. Prof. Nurse 1989, 4, 605–607.
  264. Matthes, H.; Thronicke, A.; Ralf-Dieter Hofheinz, R.-D.; Baars, E.; Martin, D.; Huber, R.; Breitkreuz, T.; Bar-Sela, G.; Glum, D.; Shad, F. Statement to an Insufficient Systematic Review on Viscum album L. Therapy. Evid.-Based Complement. Altern. Med. 2020, 2020, 7091039. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  265. Molassiotis, A.; Fernandez-Ortega, P.; Pud, D.; Odsen, G.; Scott, J.A.; Panteli, V.; Margulie, S.A.; Browall, M.; Magri, M.; Selvikprova, S.; et al. Use of complementary and alternative medicine in cancer patients: A European survey. Ann. Oncol. 2005, 16, 655–663. [Google Scholar] [CrossRef] [PubMed]
  266. Bar-Sela, G.; Wollner, M.; Hammer, L.; Agbarya, A.; Dudnik, E.; Haim, N. Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: A randomised phase II study. Eur. J. Cancer 2013, 49, 1058–1064. [Google Scholar] [CrossRef] [PubMed]
  267. Casetti, F.; Rafei-Shamsabadi, D.; Müller, S. Grade II-anaphylaxis after subcutaneous injection of mistletoe extract. Contact Dermat. 2021, 85, 462–465. [Google Scholar] [CrossRef]
  268. Stoss, M.; Van Wely, M.; Musielsky, H.; Gorter, R.W. Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks. Arzneimittelforschung 1999, 49, 366–373. [Google Scholar] [CrossRef]
  269. Finall, A.I.; McIntosh, S.A.; Thompson, W.D. Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract. BMJ 2006, 333, 1293. [Google Scholar] [CrossRef] [Green Version]
  270. Steele, M.L.; Axtner, J.; Happe, A.; Kroz, M.; Matthes, H.; Schad, N. Adverse drug reactions and expected effects to therapy with subcutaneous mistletoe extracts (Viscum album L.) in cancer patients. Evid. Based Complement. Altern. Med. 2014, 2014, 724258. [Google Scholar] [CrossRef] [Green Version]
  271. Schläppi, M.; Ewald, C.; Kuehn, J.J.; Weinert, T.; Thuber, R. Fever therapy with intravenously applied mistletoe extracts for cancer patients: A retrospective study. Integr. Cancer Ther. 2017, 16, 479–484. [Google Scholar] [CrossRef] [Green Version]
  272. Hutt, N.; Kopferrschitt-Kobler, M.C.; Cabalion, J.; Purohit, A.; Alt, M.; Pauli, G. Anaphylactic reaction after therapeutic injection of mistletoe (Viscum album L.). Allergol. Immunopathol. 2001, 29, 201–203. [Google Scholar] [CrossRef]
  273. Stein, G.M.; Pfüller, U.; Schietzel, M. Viscotoxins-free aqueous extracts from European mistletoe (Viscum album L.) stimulate activity of human granulocytes. Anticancer Res. 1999, 19, 2925–2928. [Google Scholar]
  274. Giudici, M.; Pascual, R.; Canal, L.; Pfuller, K.; Pfuller, U.; Villalain, J. Interaction of Viscotoxins A3 and B with Membrane Model Systems: Implications to their mechanism of action. Biophys. J. 2003, 85, 971–981. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  275. Johannes, L.; Jacob, R.; Leffer, H. Galectins at a Glance. J. Cell Sci. 2018, 131, jcs208884. [Google Scholar] [CrossRef] [Green Version]
  276. Gengebach, B.B.; Linda, L.K.; Buyel, J.F.; Muscen, C.R.; Melmer, G.; Lentzen, H.; Buhrmann, J.; Buyel, J.F. Comparison of microbial and transient expression (tobacco plants and plant-cell) for production and purification of the anticancer mistletoe lectin viscumin of the anticancer mistletoe Viscumin. Biotechnol. Bioeng. 2019, 116, 2236–2249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  277. Sholova, N.; Bovm, N.; Maltseva, D.; Polyakova, S.; Sablina, M.; Niwa, H.; Zakharova, G.; Raygorodskaya, M.; Bufeeva, L.; Belyi, Y.; et al. Specificity of viscumin reversed. As probed with a printed glycan array. Biochimie 2022, 202, 94–102. [Google Scholar] [CrossRef] [PubMed]
  278. Schotterl, S.; Hubner, M.; Armento, A.; Vininga, V.; Wirsik, N.M.; Bernatz, S.; Lentzen, H.; Mittelbronm, M.; Naumann, U. Viscumins functionally modulate cell mobility-associated gene expression. Int. J. Oncol. 2017, 50, 684–696. [Google Scholar] [CrossRef] [Green Version]
  279. Schöffski, P.; Riggert, S.; Fumoleau, P.; Campone, M.; Bolte, O.; Marreaud, S.; Lacombe, D.; Baron, B.; Herold, M.; Zwierzina, H.; et al. Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: A study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Ann. Oncol. 2004, 15, 1816–1824. [Google Scholar] [CrossRef] [PubMed]
  280. Fritz, P.; Seizer-Schmidt, R.; Mürdter, T.E.; Kroemer, H.K.; Aulitzky, W.; André, S.; Gabius, H.J.; Friedel, G.; Toomas, H.; Siegel, I. Ligands for Viscum album agglutinin and galectin-1 in human lung cancer: Is there any prognostic relevance? Acta Histochem. 1999, 101, 239–253. [Google Scholar] [CrossRef]
  281. Gabias, H.-J. Probing the cons and the pros of lectin-induced immunomodulation: Case studies of the mistletoe lectin and galectin-1. Biochimie 2001, 83, 659–666. [Google Scholar] [CrossRef]
  282. Lenartz, D.; Stoffel, B.; Menzel, J.; Beuth, J. Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destruction therapy in glioma patients. Anticancer Res. 1996, 16, 3799–3802. [Google Scholar]
  283. Hostanska, K.; Hajto, T.; Weber, K.; Fischer, J.; Lentzen, H.; Sutterlin, B.; Saller, R. A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine thymocytes. Nat. Immun. 1996, 15, 295–311. [Google Scholar]
  284. Chou, F.-C.; Chen, H.-Y.; Kuo, C.-C.; Sytwu, H.-K. Role of Galectins in Tumors and in Clinical Immunotherapy. Int. J. Mol. Sci. 2018, 19, 430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  285. Rabinovich, G.A.; Toscano, M.A. Turning “sweet” immunology: Galectin-glycan interactions in immune tolerance and inflammation. Nat. Rev. Immunol. 2003, 9, 338–352. [Google Scholar]
  286. Jing Hong, J.; Meng, L.; Yu, P.; Zhou, C.; Yu, Z.; Zhao, Y. Novel drug isolated from mistletoe (1 E,4 E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: Synthesis, pharmacokinetics and pharmacodynamics. RCS Adv. 2020, 10, 27794–27804. [Google Scholar] [CrossRef] [PubMed]
  287. Byeon, S.E.; Lee, J.; Yu, T.; Cho, J.-Y. Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Lectin-Mediated Regulation of Macrophage Functions. Biomol. Ther. 2009, 17, 293–298. [Google Scholar] [CrossRef] [Green Version]
  288. Korcan, S.E.; Cankaya, N.; Arzarkhan, S.Y.; Bulduk, I.; Karaaslan, E.C.; Kargioglu, M.; Konik, M.; Guvercin, G. Determination of Antioxidant Activities of Viscum album L.: First Report on Interaction of Phenolics with Survinin Protein using in Silico Analysis. ChemistrySelect 2023, 8, e202300130. [Google Scholar] [CrossRef]
  289. Schad, F.; Steinmann, D.; Oei, S.L.; Thronicke, A.; Grah, C. Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L.: A real-world data study. Radiat. Oncol. 2023, 18, 47. [Google Scholar] [CrossRef]
Table 1. Reported anti-inflammatory activities of extracts of European mistletoe (VA) and Korean mistletoe.
Table 1. Reported anti-inflammatory activities of extracts of European mistletoe (VA) and Korean mistletoe.
Part of the PlantReported ActivityActive ConstituentsReference
VA hydro-alcoholic extractAnti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2Total extract[135]
VA hydro-alcoholic extractInhibition of cytokine-induced PGE2 via selective inhibition of COX-2 and destabilization of COX-2 mRNA Total extract[136]
Aqueous extractProliferation and cytokine synthesis of splenocytesTotal extract[137]
VA hydro-alcoholic extractDestabilization of COX-2 mRNATotal extract[138]
KV mistletoe extractIncrease in the levels of serum inflammatory cytokinesTotal extract[139]
VA ethanolic extract of leaves and twigsAnti-inflammatory activityFree and glycoside flavonoids[141]
VA hydro-alcoholic extractInduction apoptosis of preactivated neutrophils in vivo without pro-inflammatory responseAgglutinin-I (VAA-I)[142]
VA hydro-alcoholic extracteEffect on human peripheral blood lymphocytesAgglutinin-I (VAA-I)[171]
Table 2. Reported anti-oxidation activities of extracts of Viscum album (VA).
Table 2. Reported anti-oxidation activities of extracts of Viscum album (VA).
Part of the PlantReported ActivityActive ConstituentsReference
VA extract of leaves and stemsAntioxidant activityTotal phenols[143]
VA methanolic extractInhibitory effect on lipid peroxidationTotal extract[144]
VA methanolic extractAntiproliferative and antioxidant properties in vitroMethanolic extract[145]
VA ethanolic extractIncreased percentage of low plasma antioxidant activityeEhanolic extract[146]
VA methanolic extractAntioxidant activity and scavenging activityMethanolic extract[147]
VA aqueous extractsAntioxidant and anti-inflammatory activitiesPhenolic acids, phenylpropanoids and flavonoids[148]
VA aqueous extractsAntioxidant activityPolyphenols and flavonoids[149]
VA alcoholic extractsAntioxidant activity and scavenging activityPolyphenols and flavonoids[150]
VA aqueous and ethanolic extractsAntioxidant activityTotal extract[155]
VA aqueous extract of leavesAntioxidant activityTotal extract[156]
VA aqueous and methanolic extractsAntioxidant activityTotal extracts and phenols[158]
VA crude extractAntioxidant activityPhenols[159]
KV mistletoe extractOverexpressions of cyclooxygenase-2 and inducible NO synthaseLectins[141]
KV extractAntioxidant activityCaffeic acid and lyoniresinol[165]
VA ethanolic extractInhibition of ADP-induced platelet aggregationPhenylpropanoid glycosides [166]
VA extract of leavesAntioxidant activityRamnazin glucosides[167]
Methanol extract of whole shrubAntioxidant activityPhenols[168]
VA methanol extract aerial partsAntioxidant activityTotal extract[172]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Nicoletti, M. The Anti-Inflammatory Activity of Viscum album. Plants 2023, 12, 1460.

AMA Style

Nicoletti M. The Anti-Inflammatory Activity of Viscum album. Plants. 2023; 12(7):1460.

Chicago/Turabian Style

Nicoletti, Marcello. 2023. "The Anti-Inflammatory Activity of Viscum album" Plants 12, no. 7: 1460.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop