Mistletoe–host systems exemplify an intimate and chronic relationship where mistletoes represent protracted stress for hosts, causing long‐lasting impact. Although host changes in morphological and ...reproductive traits due to parasitism are well known, shifts in their physiological system, altering metabolite concentrations, are less known due to the difficulty of quantification. Here, we use ecometabolomic techniques in the plant–plant interaction, comparing the complete metabolome of the leaves from mistletoe (Viscum album) and needles from their host (Pinus nigra), both parasitized and unparasitized, to elucidate host responses to plant parasitism. Our results show that mistletoe acquires metabolites basically from the primary metabolism of its host and synthesizes its own defence compounds. In response to mistletoe parasitism, pines modify a quarter of their metabolome over the year, making the pine canopy metabolome more homogeneous by reducing the seasonal shifts in top‐down stratification. Overall, host pines increase antioxidant metabolites, suggesting oxidative stress, and also increase part of the metabolites required by mistletoe, which act as a permanent sink of host resources. In conclusion, by exerting biotic stress and thereby causing permanent systemic change, mistletoe parasitism generates a new host‐plant metabolic identity available in forest canopy, which could have notable ecological consequences in the forest ecosystem.
This study shows that mistletoe causes changes in pine host metabolome and generates a new plant metabolic identity in forest canopy, highlighting the important role of mistletoe in increasing the complexity and heterogeneity of the forest canopy. Therefore, by triggering a cascade of ecological consequences, mistletoe can have valuable implications for the conservation and management of pine forests.
Viscum album L. (Santalaceae) is an important medicinal plant traditionally used to treat several diseases, including cancer therapy. This paper provides detailed morpho-anatomical characteristics of ...the leaves, stems and berries of Viscum album subsp. album growing as hemi-parasite on the branches of Malus domestica (Suckow) Borkh. (Rosaceae) to aid species identification and botanical characterization. Additionally, for the first time, microchemical analyses of all tissues and Energy Dispersive X-Ray Spectroscopy analyses of the calcium oxalate crystals are provided for the first time. The plant features leathery presents green leaves with parallel veins, small yellow unisexual flowers in 3-flowered cymes, and the dioecious inflorescences usually consist of three flowers, with female flowers generating white fleshy berries, in which a seed is embedded in the mucilaginous mesocarp, normally containing two embryos. Anatomically, the analyzed leaves were isobilateral and amphistomatic, and showed straight anticlinal epidermal cell walls, thick cuticles with epicuticular wax crystalloids, and paracytic stomata. The midrib is flat on both sides and has a single vascular bundle, whereas the strongly shortened petiole is concave-convex in shape and contains five bundles. The stems show a primary structure with a ring of nine vascular bundles enclosing the pith. Calcium oxalate druses and cubic and quadrangular prisms were observed in different plant parts. The results of this study provide new microscopy information that can help in the authentication of mistletoe raw materials.
Background: Viscum album L (VA, mistletoe) extracts are commonly used in integrative oncology. Here the clinical safety profile of additional VA-treatments to standard care in cancer patients with ...preexisting autoimmune diseases was analyzed. Methods: In this observational cohort study medical data and recorded adverse events (AEs) of treated patients were retrieved from the Network Oncology registry and a safety analysis was performed. Results: A total of 106 patients (median age 63 years) treated with add-on VA-extracts were analyzed. Most frequent autoimmune diseases were Hashimoto’s thyroiditis (27%), psoriasis (19%), and ulcerative colitis (15%). Seventeen patients (16%) experienced VA-related AEs, but neither long-term side effects nor VA-therapy discontinuations were recorded. In a subgroup of 30 patients receiving long-term VA-therapy no exacerbations or flares of underlying autoimmune diseases were recorded. Additionally, a significant halving of overall AE-rates was observed during VA-treatment periods (p= 0.019). Conclusions: Our findings suggest that add-on VA-therapy in cancer patients with preexisting autoimmune diseases as Hashimoto’s thyroiditis, psoriasis, ulcerative colitis, Grave’s disease, and some rheumatic diseases is safe. No higher rates of VA-associated AEs were observed and the overall AE-rates were significantly lowered in VA-therapy periods. However, results should be interpreted with caution in light of the study’s observational character.
A majority of oncological patients apply add-on white-berry European mistletoe (Viscum album L., VA) extracts to reduce disease- and treatment-related symptoms and to improve health-related quality ...of life (HRQL). VA extracts exert various antitumor, pro-apoptotic, anti-proliferative, and immunomodulatory effects. Two current meta-analyses attribute life-prolonging and HRQL-improving properties to additive VA therapy. The aim of the present update was to review the current knowledge on VA extracts in clinical oncology. Hereby, we concentrated on studies with the highest clinical relevance in the field of lung, gastric, colorectal and pancreatic, gynaecological, as well as breast cancer applying the anthroposophical mistletoe preparations.
The present update provides a brief overview regarding the use of VA preparations in clinical oncology reviewing current guidelines, systematic reviews, randomized controlled and real-world data studies. We have searched the pubmed.gov database of the National Library of Medicine with the search terms "mistletoe" and "cancer." We found good evidence of add-on VA therapy to improve the HRQL of patients with breast cancer (American Society of Clinical Oncology - endorsed Society for Integrative Oncology guideline) and of HRQL-improving and survival-prolonging properties of VA therapy in pancreatic cancer. In the field of gastrointestinal, gynaecological, and lung cancer, new or updating integrative and/or oncological guidelines should consider clear recommendations on integrative therapies including VA therapy. Nevertheless, further clinical and real-world data trials need to be performed in this field.
Evidence for add-on VA treatment for the improved management of cancer and cancer-related side effects is accumulating. Patients with breast cancer: good evidence for add-on VA therapy to improve the HRQL of oncological patients. Patients with pancreatic cancer: good evidence for add-on VA to improve HRQL and prolong survival. Patients with gastrointestinal, gynaecological, and lung cancer: update of guidelines is recommended with regards to integrative oncological therapies including add-on VA.
Fermented aqueous extracts of
L. are widely used for cancer treatment in complementary medicine. The high molecular weight compounds viscotoxins and lectins are considered to be the main active ...substances in the extracts. However, a vast number of small molecules (≤1500 Da) is also expected to be present, and few studies have investigated their identities. In this study, a comprehensive metabolome analysis of samples of fermented aqueous extracts of
from two host tree species (
and
), both prepared by two pharmaceutical manufacturing processes, was performed by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). A total of 212 metabolites were putatively annotated, including primary metabolites (e.g., amino acids, organic acids, etc.) and secondary metabolites (mostly phenolic compounds). A clear separation between
samples according to the host tree species, but not due to manufacturing processes, was observed by principal component analysis. The biomarkers responsible for this discrimination were assessed by partial least squares-discriminant analysis. Because
extracts from different host trees have different clinical applications, the present work highlights the possibility of characterizing the metabolome for identification and traceability of
fermented aqueous extracts.
Background
Equine sarcoids (ES) are the most common cutaneous tumors in equids. Systemic treatment options are sparse. Subcutaneous (SC) injections of Viscum album extract (VAE) demonstrate efficacy ...as a systemic treatment directed against ES.
Objectives/Aim
To critically assess the therapeutic efficacy of orally administered VAE.
Animals
Forty‐five ES‐affected, privately owned, 3–12 year‐old horses.
Methods
A 3‐armed randomized placebo‐controlled, double‐blinded study was conducted in a double‐dummy design. Horses were subjected to oral administration and SC injections of either VAE or placebo (VAE oral/placebo SC, VAE SC/placebo oral, placebo oral/placebo SC) over a 7‐month treatment period. Primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months. Second endpoint was the clinical response.
Results
No statistically significant difference in the composite endpoint between the 3 study arms was found. The primary endpoint showed 4 (27%) horses in the VAE oral group with complete ES regression, 3 (21%) in the VAE SC injection group, and 2 (13%) in the placebo group. The clinical response revealed complete or partial regression in 6 horses of the oral VAE group (40%), 4 of the SC injection group (29%), and 4 of the placebo group (25%). Direct comparison of oral VAE and placebo showed an odds ratio, stratified for prognosis of 2.16 (95%‐CI: 0.45–10.42) and a P‐value of 0.336.
Conclusion and Clinical Importance
Oral administration of VAE is well tolerated. No statistically significant difference in the effectiveness of systemic VAE versus placebo against ES was found.
Viscum album L. is claimed in traditional medical practice, to be useful in the treatment of epilepsy and insomnia in some parts of India.
Viscum album L. is claimed in traditional medical practice, ...to be useful in the treatment of epilepsy and insomnia in Himachal Pradesh, India.
The effect of Viscum album L. on epilepsy, psychosis and sedative activity was evaluated in mice and rats using standard procedure.
The aqueous leaf extract of Viscum album L. prolonged the pentobarbital induced sleeping time and reduced the locomotor activity in actophotometer. This suggests that reduced locomotor activity facilitate GABAergic transmission. In addition the extract reduced MES, INH and PTZ-induced convulsions which suggest that there may be possibility of blocking Na+ channels, opening of Cl−channels or enhancing the GABAergic system. The extract decreased the apomorphine-induced stereotyped behavior and potentiates the HAL-induced cataleptic score which suggests the extract possess antidopaminergic activity.
The results obtained in present study suggested that title plant exhibited sedative, antiepileptic and antipsychotic activity in mice and rats.
Viscum album L. (Santalaceae), commonly known as mistletoe, is a hemiparasitic plant traditionally used in complementary cancer treatment. Its antitumor potential is mostly attributed to the presence ...of aqueous soluble metabolites; however, the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential. The clinical efficacy of mistletoe therapy inspired the present work, which focuses on ethanolic extracts (V. album "mother tinctures", MT) prepared from different host trees.
Samples from three European subspecies (album, austriacum, and abietis) were harvested, and five different V. album-MT strains were prepared. The following phytochemical analyses were performed: thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proliferation assay was performed with WST-1 after incubation of tumor (Yoshida and Molt-4) and fibroblast cell lines (NIH/3 T3) with different MT concentrations (0.5 to 0.05% v/v). The cell death mechanism was investigated by flow cytometry (FACS) using Annexin V-7AAD.
Chemical analyses of MT showed the presence of phenolic acids, flavonoids and lignans. The MT flavonoid and viscotoxin contents (mg/g fresh weight) were highest in Quercus robur (9.67 ± 0.85 mg/g) and Malus domestica (3.95 ± 0.58 mg/mg), respectively. The viscotoxin isoform proportions (% total) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba (60.57 ± 2.13). The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects of MT. The cell death mechanisms evaluated by colorimetric and FACS methodologies involved necrotic damage, which was host tree-, time- and dose- dependent, with different selectivity to tumor cells. Mother tincture from V. album ssp. abietis was the most effective at inducing in vitro cellular effects, even when incubated at the smallest concentration tested, probably because of the higher content of VT A3.
Our results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects.
The genus Viscum comprises approximately 100 species that are mainly distributed across Africa, Asia and Europe. The extracts and preparations of Viscum species are widely used as common ...complementary and alternative medicines in the treatment of rheumatism and cancer.
This review aims to explore the medicinal properties of twelve species belonging to the genus Viscum for potential therapeutic applications.
We collected online information (including PubMed, CNKI, Google Scholar, and Web of Science) from January 1915 to April 2021 and knowledge from classical books on Chinese herbal medicines available for 12 species of the genus Viscum, including Viscum coloratum (Kom.) Nakai, Viscum album L., Viscum articulatum Burm. f., Viscum liquidambaricola Hayata, Viscum ovalifolium DC., Viscum capitellatum Sm., Viscum cruciatum Sieber ex Boiss., Viscum nudum Danser, Viscum angulatum B.Heyne ex DC., Viscum tuberculatum A.Rich., Viscum multinerve Hayata, and Viscum diospyrosicola Hayata.
At least 250 different compounds have been reported across twelve Viscum species, including amino acid and peptides, alkaloids, phenolic acids, flavonoids, terpenoids, carbohydrates, fatty acids, lipids, and other types of compounds. In particular, for Viscum coloratum (Kom.) Nakai and Viscum album L., the plants, preparations, and bioactive components have been thoroughly reviewed. This has allowed to elucidate the role of active components, including lectins, viscotoxins, flavonoids, terpenoids, phenolic acids, and polysaccharides, in multiple bioactivities, such as anti-cancer, anti-rheumatism arthralgia, anti-inflammation, anti-cardiovascular diseases, enhancing immunity, and anti-chemotherapy side effects. We also evaluated quality control methods based on active compounds, in vivo exposure compounds, and discriminated chemical markers.
This is the first report to systematically review the pharmaceutical development history, chemical composition, clinical evidence, pharmacological activity, discriminated chemical markers, in vivo exposure, and quality control on twelve distinct species of Viscum plants with medicinal properties. The significant safety and efficacy, along with the minor side effects are constantly confirmed in clinics. The genus Viscum is thus an important medicinal resource that is worth exploring and developing in future pharmacological and chemical studies.
•Systematically summarized 250 chemical components and medicinal functions of 12 medicinal plants of the genus Viscum.•Explained the chemical distinguishing markers of medicinal plants of the genus Viscum.•Summarized the research on quality control and in vivo disposal of the genus Viscum.
Viscum album L. (European mistletoe), a member of the Santalaceae, is a hemiparasitic, evergreen shrub growing on deciduous and coniferous trees. In traditional and folk medicine, mistletoe was used ...for the treatment of central nervous system disorders such as epilepsy, hysteria, insomnia, nervous excitability, neuralgia, headache, dizziness and fatigue. However, relatively little is known of its neuropharmacological activity.
The aim of the present study was to evaluate the effect of treatment with aqueous and hydroethanolic extracts from Viscum album L. parasitizing birch, linden and pine, on MAO-A and MAO-B activity as well as serotonin, dopamine and serotonin receptor 5-HTR1A levels in Galleria mellonella (Lepidoptera) larvae.
The phytochemical composition of the extracts was characterised using UPLC-DAD-ESI-MS/MS. To investigate the neuropharmacological activity of Viscum album L. extracts, Galleria mellonella (Lepidoptera) larvae were used as a model organism. The inhibitory potential of the extracts against MAO-A and MAO-B was determined by fluorometry. The serotonin, dopamine and serotonin receptor 5-HTR1A levels in larvae hemolymph after treatment were quantified by ELISA.
UPLC-DAD-ESI-MS/MS analysis allowed the identification of 88 compounds, either full or in part. Most of the characterised phytochemicals were flavonoids, hydroxycinnamic acids and lignans. Screening found that aqueous and hydroethanolic mistletoe extracts inhibited the enzymatic activity of either MAO-A or MAO-B or both. Additionally, mistletoe extract administration increased the levels of serotonin and serotonin receptor 5-HTR1A. None of the tested extracts had any significant effect on dopamine level.
A key novel finding was that the aqueous and hydroethanolic extracts from Viscum album L. inhibited monoamine oxidase activity and increased the levels of serotonin and serotonin receptor 5-HTR1A in Galleria mellonella (Lepidoptera) larvae. These properties may be due to the presence of phenolic constituents, particularly flavonoids. Further research based on bioassay-guided fractionation of mistletoe is needed to identify CNS-active molecules.
Display omitted
PDF
