The essential oil compositions of three Sicilian accessions of Viscum album L. growing on three different host trees.

Viscum album L., (Common Mistletoe), is a hemiparasitic shrub that lives on a wide range of woody plant species, known since Neolithic period for its ritual and for pharmacological properties. Up to now, no investigation has been reported on the chemical composition of the essential oils of V. album aerial parts in relation with the diverse host trees. Consequently, the essential oils compositions of three Sicilian accession of V. album, growing on Quercus suber L., Crataegus monogyna Jacq. and Olea europaea L. var. europaea cv. 'Santagatese', respectively, were evaluated by GC-MS. The three populations showed quite different profiles indicating that the nature of the host considerably influences the chemical composition of the guest plant, V. album.

Phytochemical screening and effect of Viscum album L. on monoamine oxidase A and B activity and serotonin, dopamine and serotonin receptor 5-HTR1A levels in Galleria mellonealla (Lepidoptera).

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Potential Role of Korean Mistletoe Extract as an Anti-Inflammatory Supplementation.

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.

Impact of Harvest Conditions and Host Tree Species on Chemical Composition and Antioxidant Activity of Extracts from Viscum album L.

The content of plant secondary metabolites is not stable, and factors such as the region/location effect and seasonal variations have an impact on their chemical composition, especially in parasitic plants. Research in this area is an important step in the development of quality parameter standards of medicinal plants and their finished products. The effects of the time and place of harvest and the host tree species on the chemical composition and antioxidant activity of mistletoe extracts were investigated. Statistical tools were used to evaluate the results of the spectrophotometric and LC-ESI-MS/MS studies of the phenolic composition and antioxidant activity. The investigations indicate that the qualitative and quantitative composition, influencing the biological activity of mistletoe extracts, largely depends on the origin of the plant. The mistletoe extracts exhibited a rich phenol profile and high antioxidant activity. The chemometric analysis indicated that mistletoe collected from conifers (Viscum abietis and Viscum austriacum) had the most advantageous chemical composition and antioxidant activity. Moreover, the chemical profile and biological activity of the plant material were closely related to the climatic conditions and location of the harvested plant. Higher levels of phenolic compounds and high antioxidant activity were found in extracts obtained from plant material collected in cold weather with the presence of snow and less sunshine (autumn-winter period).

Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mistletoe-Extract Drugs Stimulate Anti-Cancer Vγ9Vδ2 T Cells.

Human phosphoantigen-reactive Vγ9Vδ2 T cells possess several characteristics, including MHC-independent recognition of tumor cells and potent killing potential, that make them attractive candidates for cancer immunotherapeutic approaches. Injectable preparations from the hemi-parasite plant Viscum album L. (European mistletoe) are commonly prescribed as complementary cancer therapy in European countries such as Germany, but their mechanism of action remains poorly understood. Here, we investigated in-depth the in vitro response of human T cells towards mistletoe-extract drugs by analyzing their functional and T-cell-receptor (TCR) response using flow cytometry and high-throughput sequencing respectively. Non-fermented mistletoe-extract drugs (AbnobaViscum), but not their fermented counterparts (Iscador), induced specific expansion of Vγ9Vδ2 T cells among T cells. Furthermore, AbnobaViscum rapidly induced the release of cytotoxic granules and the production of the cytokines IFNγ and TNFα in Vγ9Vδ2 T cells. This stimulation of anti-cancer Vγ9Vδ2 T cells was mediated by the butyrophilin BTN3A, did not depend on the accumulation of endogenous phosphoantigens and involved the same Vγ9Vδ2 TCR repertoire as those of phosphoantigen-reactive Vγ9Vδ2 T cells. These insights highlight Vγ9Vδ2 T cells as a potential target for mistletoe-extract drugs and their role in cancer patients receiving these herbal drugs needs to be investigated.

Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action.

Mistletoe has been used as treatment of many diseases in traditional and folk medicine. To date, anticancer, immunomodulatory, cardiac, antidiabetic, hepatoprotective, neuropharmacological, antibacterial and antifungal properties of mistletoe extracts have been studied the most. In this review, we summarized in vitro and in vivo studies on the pharmacological activity of Viscum species. Furthermore, we proposed the possible mechanisms of action of this herb, which might include many signalling pathways. Mistletoe could regulate either similar or different targets in various pathways that act on membrane receptors, enzymes, ion channels, transporter proteins and transcriptional targets. Still, pharmacological activities of mistletoe have been investigated mainly for crude extracts. It is a new field for scientists to determined which chemical compounds are responsible for the individual biological activities of mistletoe and how these activities are achieved. As a result, mistletoe might become a source of new complementary therapies supporting the treatment of many diseases.

[Mistletoe in the treatment of cancer patients]. / Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung.

Mistletoe (Viscum album L.) continues to be the medical herb prescribed most frequently for cancer patients in German-speaking countries. Demand for this therapy often comes from patients themselves and requires careful consideration by the attending physician during consultation.In German-speaking countries, mistletoe extracts are available as approved drugs (based on monographs of the commissions C and E of the German Federal Institute for Drugs and Medical Devices). In Switzerland, treatment costs are generally covered by statutory health insurance. In Germany, coverage is limited to palliative care. In adjuvant cases, treating physicians can request coverage by the health insurance if patients suffer from side effects due to the antitumoral treatment.The spectrum of Viscum album extract includes mistletoe lectin I; II, and III, viscotoxins, flavonoids, amino acids, polysaccharides, and membrane lipids. Preclinical studies have demonstrated cytotoxic, apoptosis-inducing, and immunomodulatory effects.Many clinical studies indicate a supportive efficacy of mistletoe extracts in tumor patients, even though methodological quality is discussed controversially in many cases. Clinical data regarding effects on survival of patients is inconsistent; effects concerning quality of life as well as the tolerability of antitumoral treatments are evaluated more positively.In view of the high demand on the patient side and increasing scientific evidence, the general conditions for prescriptions should continue as well as the ongoing scientific evaluation.

Velutin, an Aglycone Extracted from Korean Mistletoe, with Improved Inhibitory Activity against Melanin Biosynthesis.

The abnormal regulation of melanin synthesis leads to a wide range of pigmentary disorders. Although various melanin biosynthesis inhibitors have been developed, their efficacy and long-term safety needs to be further improved, and thus the goal of this study is to develop promising natural compound inhibitors of melanin biosynthesis. Here, we obtained aglycone flavonoid extract through the microwave-assisted hydrolysis of glycoside extract from Korean mistletoe in acidic condition. The aglycone extract inhibited tyrosinase activity more efficiently with better antioxidant activity than glycoside extract in vitro. The microwave-assisted aglycone extract of mistletoe was further analyzed for in vivo activity, and the results showed the aglycone extract inhibited both early melanocyte development and melanin synthesis more efficiently in zebrafish embryo in a dose-dependent manner. Our in vivo toxicity assay quantitatively measured cell death in zebrafish embryos and showed that the microwave-assisted aglycone extract of mistletoe had no significant effect on cell death (p < 0.001), indicating that aglycone extract is more biocompatible than glycoside extract. Furthermore, our in vitro and in vivo analyses successfully identified and characterized velutin, an aglycone of a homoflavoyadorinin B glycoside, as a major inhibitory component in the microwave-assisted mistletoe extract. Ultimately, this study showed that the novel natural compound inhibitor velutin, which was generated through microwave-assisted extraction from mistletoe, improved the efficacy of melanin biosynthesis inhibition with little toxicity.

Polysaccharide fraction from the Indian mistletoe, Dendrophthoe falcata (L.f.) Ettingsh enhances innate immunity and disease resistance in Oreochromis niloticus (Linn.).

The polysaccharide fraction (PF) isolated from the hemiparasitic mistletoe, Dendrophthoe falcata (L.f.) Ettingsh (DF) leaves was tested for its immunostimulatory properties in Oreochromis niloticus (Linn.). Different groups of experimental fish were fed for 1, 2 or 3 weeks with three different doses [low (0.01%), mid (0.1%), or high (1%)] of D. falcata polysaccharide fraction (DFPF) - supplemented diet. After every feeding regimen, the fish were assessed for non-specific immunological parameters, immune related gene expression and disease protection. The DFPF treated groups showed significant (P < 0.05) enhancement of non-specific immune parameters. Significant (P < 0.05) upregulation of lysozyme and TNF-α gene expression was observed in DFPF treated groups. In pathogen challenge studies using Aeromonas hydrophila, the DFPF treated groups displayed significant (P < 0.05) decrease in percentage mortality and the consequent increase in relative percent survival (RPS). Supplementation of 1% DFPF in the feed for a week conferred the maximum protection against the virulent pathogen challenge, recording a RPS of 100. These results suggest that DFPF has the potential to be used as an immunostimulating feed additive in finfish aquaculture.

Therapeutic potential of mistletoe in CNS-related neurological disorders and the chemical composition of Viscum species.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum album L., commonly known as mistletoe, has been used for centuries in traditional medicine to treat various neurological diseases, including epilepsy, hysteria, nervousness, hysterical psychosis, dizziness and headaches. AIM OF THE STUDY: The aim of this review is to summarize existing evidence confirming the influence of mistletoe on the central nervous system and to investigate the compounds that may be responsible for this activity. MATERIALS AND METHODS: Available information from studies of various species of the Viscum L. genus was collected from scientific journals, books, and reports via a library and an electronic data search (Elsevier, Google Scholar, PubMed, Springer, Science Direct, ResearchGate, and ACS). RESULTS: The main chemical constituents of Viscum L. species are viscotoxins, lectins, flavonoids, phenolic acids, terpenoids, sterols, phenylpropanoids, and alkaloids. Various extracts of Viscum album L. showed central nervous system activity, including antiepileptic, sedative, antipsychotic, anxiolytic, antidepressant and antinociceptive effects in mice and rats. Additionally, the extracts increased the level of brain-derived neurotrophic factor, prevented apoptotic neuronal death induced by amyloid ß and weakly inhibited cholinesterase activity. CONCLUSIONS: Numerous historical references describe the use of mistletoe for the treatment of central nervous system disorders. In recent years, studies have started to confirm the antiepileptic, antipsychotic, sedative and antinociceptive effects of mistletoe. Additionally, mistletoe can be used as a complementary treatment for Alzheimer's disease. The therapeutic effect of mistletoe might be a result of the synergistic interactions of various secondary metabolites, including mistletoe-specific lectins. Further studies of the chemical composition and CNS activity of mistletoe are required. The mechanisms of action, target sites, pharmacokinetics, metabolic mechanisms, adverse effects and interactions of mistletoe with other drugs must also be investigated, as well.

The Stability of Medicinal Plant microRNAs in the Herb Preparation Process.

Herbal medicine is now globally accepted as a valid alternative system of pharmaceutical therapies. Various studies around the world have been initiated to develop scientific evidence-based herbal therapies. Recently, the therapeutic potential of medicinal plant derived miRNAs has attracted great attraction. MicroRNAs have been indicated as new bioactive ingredients in medicinal plants. However, the stability of miRNAs during the herbal preparation process and their bioavailability in humans remain unclear. Viscum album L. (European mistletoe) has been widely used in folk medicine for the treatment of cancer and cardiovascular diseases. Our previous study has indicated the therapeutic potential of mistletoe miRNAs by using bioinformatics tools. To evaluate the stability of these miRNAs, various mistletoe extracts that mimic the clinical medicinal use as well as traditional folk medicinal use were prepared. The mistletoe miRNAs including miR166a-3p, miR159a, miR831-5p, val-miR218 and val-miR11 were quantified by stem-loop qRT-PCR. As a result, miRNAs were detectable in the majority of the extracts, indicating that consumption of medicinal plant preparations might introduce miRNAs into mammals. The factors that might cause miRNA degradation include ultrasonic treatment, extreme heat, especially RNase treatment, while to be associated with plant molecules (e.g., proteins, exosomes) might be an efficient way to protect miRNAs against degradation. Our study confirmed the stability of plant derived miRNAs during herb preparations, suggesting the possibility of functionally intact medicinal plant miRNAs in mammals.

Comparative Evaluation of Soluble and Insoluble-Bound Phenolics and Antioxidant Activity of Two Chinese Mistletoes.

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble and insoluble-bound phenolic extracts from CMs hosted by Camellia assamica (Mast.) Chang (CMC) and Pyrus, i, f. (CMP) were compared. Phenolic compounds in CMC and CMP were identified and quantified using high-performance liquid chromatography (HPLC). The results indicated that the TPC of soluble phenolic extracts was higher than insoluble-bound phenolic counterparts in both CMC and CMP. In addition, the TPC of soluble, insoluble-bound and total phenolic fractions (9.91 ± 0.23, 4.59 ± 0.27 and 14.50 ± 0.35 µmol ferulic acid equivalents per gram (FAE/g) dry sample) extracted from CMP were higher than those extracted from CMC. The soluble phenolic extracts in CMP showed higher antioxidant activities than those in CMC. Eighteen phenolic compounds from soluble and insoluble-bound phenolic extracts from the CMs were identified and quantified by HPLC. This study indicates that CMC and CMP, especially the latter, could be sources of antioxidants in human health care.

Determination of Heavy Metals in Almonds and Mistletoe as a Parasite Growing on the Almond Tree Using ICP-OES or ICP-MS.

In this study, the elements of Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Ni, Sr, Pb, Ti, and Zn were determined in the leaves, fruits, and branches of mistletoe, (Viscum albüm L.), used as a medicinal plant, and in the leaves, branches and barks of almond tree which mistletoe grows on. The aim of the study is to investigate whether the mistletoe are more absorbent than the almond tree in terms of the heavy metal contents and the determination of the amount of the elements penetrated into the mistletoe from the almond tree. ICP-MS (inductively coupled plasma-mass spectrometry) was used for the analysis of As, Cd, Mo, and Pb, whereas ICP-OES (inductively coupled plasma optical emission spectrometry) was used for the other elements. The results obtained were statistically evaluated at 95% confidence level. Within the results obtained in this study, it was determined whether there is a significant difference between metal elements in almond tree and mistletoe, or not. As a result, it was observed that there were higher contents of B, Ba, K, Mg, and Zn in the mistletoe than in the almond tree. K was found much higher than other elements in the mistletoe. On the other hand, Al, As, Ca, Cd, Cr, Cu, Fe, Mo, Ni, Sr, Pb, and Ti contents were determined to be more in almond tree than mistletoe.

Antiviral activity of Salidroside from the leaves of Nigerian mistletoe (Loranthus micranthus Linn) parasitic on Hevea brasiliensis against respiratory syncytial virus.

Isolated Salidroside from the leaves of Nigerian mistletoe (Loranthus micranthus Linn) parasitic on Hevea brasiliensis was evaluated for its antiviral activity against respiratory syncytial virus. Semi- preparative HPLC separation of the ethyl acetate fraction of the leave extract of Loranthus micranthus Linn parasitic on Hevea brasiliensis led to the isolation of a polyphenol. Using spectroscopic methods (1D and 2D NMR and mass spectroscopic data) as well as by comparison with literature data the structure of the compound was determined as 6-O-galloyl salidroside. The antiviral activity of the isolated compound was evaluated against the respiratory syncytial virus. The isolated Salidroside showed potent inhibition towards a recombinant straining respiratory syncytial virus with Inhibitory Concentration (IC 50) value of 10.3±1.50 µg/mL. The result indicates that Salidroside is an efficient antiviral agent against RSV infection and might be useful for the management of RSV pathogenesis.

Safety of intravenously applied mistletoe extract - results from a phase I dose escalation study in patients with advanced cancer.

BACKGROUND: Mistletoe extracts have anti-tumor properties and are approved for subcutaneous use in cancer patients. Data on Intravenous application are limited. METHODS: An aqueous extract from pine-mistletoe was used to investigate maximum tolerable dose (MTD) and safety of intravenous application. It was infused once weekly for 3 weeks in patients with advanced cancer. Any type of cancer was included; relevant exclusion criteria were concurrent chemo- or radiation therapy. The classical phase I 3 + 3 dose escalation scheme was followed. Predefined dose groups were 200, 400, 700, 1200 and 2000 mg. Maximum planned dose was 2000 mg. With the MTD three more patients should be treated for 9 weeks in order to evaluate intermediate term tolerability. Weekly during the treatment and 1 week later tolerability, clinical status, safety laboratory parameters and adverse events were documented. RESULTS: Twenty-one patients (3 in the dose groups 200, 400, 700 and 1200 mg, respectively, 9 in the dose group 2000 mg) were included. MTD was not reached. Because one dose-limiting toxicity (DLT), an allergic reaction, occurred during infusion of 2000 mg, three more patients had to be included in this dose group and tolerated it, as well as the three patients who received 2000 mg for 9 weeks. Occasionally in the dose group 2000 mg mild to moderate fever occurred. CONCLUSION: Weekly infusions of 2000 mg of the pine-mistletoe extract were tolerated and can be used in further studies but had a risk for allergic reactions and fever. German Clinical Trials Register (Trial registration number DRKS00005028).

Evaluation of the Antibacterial and Antifungal Properties of Phragmanthera capitata (Sprengel) Balle (Loranthaceae), a Mistletoe Growing on Rubber Tree, Using the Dilution Techniques.

The alarming increase in multidrug resistance of pathogenic microorganisms to conventional drugs in recent years has prompted the search for new leads in alternative remedies in natural products. Hence, this study was aimed at evaluating the antimicrobial properties of Phragmanthera capitata, a parasitic mistletoe growing on rubber trees. The in vitro antimicrobial activities of the acetone, methanol, ethanol, and aqueous extracts were investigated using five gram-negative and five gram-positive bacteria and four fungi. A 96-well resazurin broth and agar dilution techniques were used for the determination of the Minimum Inhibitory and Bactericidal Concentrations. The antibacterial activity of the organic extracts had comparative effects on all the bacteria with a MIC of 1.25 to 5 mg/mL and MBC of 2.5 to 10 mg/mL. However, the acetone extract showed higher bactericidal effect while the aqueous extract was not active. The organic solvent extracts also showed antifungal activities on two of the fungi with a MIC of 1.25 mg/mL to 10 mg/mL. However, the aqueous extract had the highest activity inhibiting all the fungi with a MIC of ≤0.3125 to 1.25 mg/mL. The study supports the ethnomedicinal claims of P. capitata as a remedy for the diseases/infections caused by these organisms.

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees.

A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) as well as an antioxidant and antiproliferative activity were evaluated for the first time. The plant material was selectively extracted using ultrasound assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC results varied from 7.146 to 9.345 mg GA g-¹ and from 1.888 to 2.888 mg Q g-1 of dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest content of phenolic acids in mistletoe berries from Populus nigra 'Italica' L. and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 µg and 5.955 µg per g dry extract, respectively). The moderate antioxidant activity of investigated extracts was obtained. The studies revealed that the examined extracts decreased the proliferation of human colon adenocarcinoma cells line LS180 in a dose-dependent manner without cytotoxicity in the human colon epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest considerable impact of polyphenols on the anticancer activity of these extracts.

Mistletoe and Garlic Extracts as Polyurethane Carriers - A Possible Remedy for Choroidal Melanoma.

BACKGROUND: Melanoma is known as the most dangerous form of skin cancer; whereas the malignant choroidal melanoma is an orphan disease known as the most common primary intraocular malignancy in adults. Literature suggests that the consumption of garlic and mistletoe leads to a reduced risk of developing cancer. OBJECTIVE: The aim of this study was the obtaining and the characterization of polymer structures containing mistletoe or garlic extract. METHODS: The structures were obtained in a polyaddition process combined with a spontaneous emulsification; they were characterized by pH, size, Zeta potential and DSC measurements, evaluation of encapsulation efficacy, penetrability through membranes and in vitro cytotoxicity tests. RESULTS: The microstructures present sizes between 1.05 and 2.60 µm and Zeta potentials between -7 and +36 mV. A good encapsulation was observed on different evaluations (88-92%). It was determined that approx. 30% of polymer microstructures containing vegetal extracts pass through an artificial membrane in 4 days. An in vitro cytotoxicity test revealed that these products are safe for administration. The analysis of antitumor efficacy indicates that garlic extracts have important effects after 48 and 72 hours on A375 cells; however, polymer microstructures with herbal extracts did not reveal antiproliferative activities on A375 cells because these polymer structures present a slow degradation. CONCLUSION: Sterile eye drops solutions based on polymer microstructures containing garlic or mistletoe extracts were obtained; the sample based on garlic extracts may be used in the pharmaceutical field as drug carrier with an antiproliferative effect which occurs after a prolong period.

In Vitro and In Vivo Anti-inflammatory Effects of Struthanthus vulgaris.

Struthanthus vulgaris is probably the most common medicinal mistletoe plant in Brazil, and has been used in folk medicine as an anti-inflammatory agent and for cleaning skin wounds. Our proposal was to evaluate the anti-inflammatory activity of S. vulgaris ethanol leaf extract and provide further insights of how this biological action could be explained using in vitro and in vivo assays. In vitro anti-inflammatory activity was preliminarily investigated in lipopolysaccharide/interferon gamma-stimulated macrophages based on their ability to inhibit nitric oxide production and tumor necrosis factor-alpha. In vivo anti-inflammatory activity of S. vulgaris ethanol leaf extract was investigated in the mice carrageenan-induced inflammation air pouch model. The air pouches were inoculated with carrageenan and then treated with 50 and 100 mg/kg of S. vulgaris ethanol leaf extract or 1 mg/kg of dexamethasone. Effects on the immune cell infiltrates, pro- and anti-inflammatory mediators such as tumor necrosis factor-alpha, interleukin 1, interleukin 10, and nitric oxide, were evaluated. The chemical composition of S. vulgaris ethanol leaf extract was characterized by LC-MS/MS. In vitro S. vulgaris ethanol leaf extract significantly decreased the production of nitric oxide and tumor necrosis factor-alpha in macrophages and did not reveal any cytotoxicity. In vivo, S. vulgaris ethanol leaf extract significantly suppressed the influx of leukocytes, mainly neutrophils, protein exudation, nitric oxide, tumor necrosis factor-alpha, and interleukin 1 concentrations in the carrageenan-induced inflammation air pouch. In conclusion, S. vulgaris ethanol leaf extract exhibited prominent anti-inflammatory effects, thereby endorsing its usefulness as a medicinal therapy against inflammatory diseases, and suggesting that S. vulgaris ethanol leaf extract may be a source for the discovery of novel anti-inflammatory agents.