In vitro evaluation of the effects of Viscum album homeopathic preparations on murine melanoma cells

Viscum album extract (VA) is a complementary treatment in cancer, with in vitro and in vivo cytotoxic effects on several tumor types when applied in phytochemical doses. However, highly diluted ethanolic homeopathic preparations' effects and mechanisms need further study. Aims:To assess the in vitro effects of highly diluted VA from the subspecies V. album abietis and V. album album at different potency levels in different dilution ratios on murine melanoma cells. Methodology:The VA mother tinctures (MT)from Abies alba (MTA) and Quercus robur (MTQ) were prepared with summer and winter samples, harvested in Switzerland. They were submitted to homeopathic ethanolic maceration and a subsequent dynamization process. MTA, MTQ and the following respective potencies were tested in B16F10 murine cells: 3x, 12x, 30x, 6cH, 12cH, 200cH, 2LM, 3LM, and 5LM. Dynamized water, dynamized and non-dynamized ethanol, and carboplatin were used as control groups. The mitochondrial activity and cell viability analysis were performed at 1, 24, 48, and 72 hours by in vitro incubation. MTA and MTQ harvested in summer, as well as 12x, 200cH and 5LM potencies were also tested to cell apoptosis and necrosis markers, reactive oxygens species (ROS) production, inflammatory cytokines profile, cell morphology, and migratory capacity. Results and discussion: MTA and MTQ induced a decrease in cell metabolism and higher cytotoxicity within 1 hour, with significant morphological changes and increased production of ROS and inflammatory cytokines. Both homeopathic dilutions 12x and 5LM showed an influence on cell metabolism, cell replication, and oxidative stress modulation with inflammatory cytokines, mitosis, and migration pattern changes. On the other hand, Quercus robur and Abies alba 200cH showed increased on cytotoxicity and ROS levels, respectively. Conclusion:The in vitro effects of Viscum album homeopathic solutions in melanoma cells highlight the promising antitumoral potential and reinforce the need for further research to better understanding their mechanisms of action.

Viscum album L. & Abies alba borisii regis effects on platelet aggregation and tumor metastasis

Viscum album L. is a widely used medicinal plant in cancer treatment, known since ancient times. The aim of this study was to investigate the antimetastatic properties of the ethanolic extracts of synergistic plants V. album L. (epiphyte) and Abies alba (host) used alone or in combination (mixture). Inhibition of platelet aggregation was evaluated in washed rabbit and human platelets. Levels of thromboxane A2 (TXA2 ) were estimated by radioimmune assay and natural killer cells (NKCs) cytotoxicity by flow cytometry. The antimetastatic properties of V. album L. and A. alba were studied in a tumor-bearing Wistar rat model. All extracts inhibited platelet aggregation in a dose-dependent manner as well as TXA2 production by three pathways of aggregation (adenosine diphosphate, platelet-activating factor, and arachidonic acid) while the mixture significantly increased NKCs cytotoxicity against cancer cells. In tumor-bearing Wistar rats, the treatment with the mixture of V. album L. and A. alba extract reduced the metastatic locations almost by 77%. These data suggest that V. album L. and A. alba extract reduced metastasis through inhibition of platelet aggregation and amplification of the body defense mechanisms against cancer cells.

Two symmetrical unsaturated acids isolated from Viscum album / 中国天然药物

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.

Three new bioactive flavonoid glycosides from Viscum album / 中国天然药物

Two new flavonoid glycosides, named viscumneoside XII (1), and viscumneoside XIII (2); a new dihydrogen flavonoid glycoside product named viscumneoside XIV (3), were isolated from the aerial part of Viscum album, along with seven known compounds (4-10). Their structures were identified by analysis of spectroscopic data. In addition, cytotoxicity assay showed that 1, 2 and 3 possessed significant inhibitory activities against C6, A549 and MDA-MB-231 (the inhibition rate arrived about 50%, 70% and 74% respectively with IC ≤ 60.00 μmol·L), while the inhibition of TF-1 and Hela was not significant.

Chemical Pleurodesis Using Doxycycline and Viscum album Extract

BACKGROUND: In chemical pleurodesis for managing pulmonary air leak, tetracycline derivatives are commonly used, and their effectiveness has been established in many studies. Recently, a Viscum album extract was used in chemical pleurodesis. We compared the effects of V. album with those of a tetracycline derivative (doxycycline) to demonstrate the therapeutic effectiveness of the V. album extract in chemical pleurodesis for managing pulmonary air leak. METHODS: Between October 2010 and October 2016, chemical pleurodesis was performed using doxycycline in 40 patients and the V. album extract in 37 patients. Thirty-three patients were in the postoperative state after pulmonary resection, and 44 patients suffered from spontaneous pneumothorax. RESULTS: No statistically significant difference in the success rate was observed between the 2 groups (V. album extract and doxycycline). In both groups, chest pain was the most common complication. More patients in the doxycycline group complained of severe chest pain (42.1% vs. 13.5%, p=0.006). In the V. album extract group, 24.3% of the patients required a chest tube to drain the pleural effusion after cessation of the air leak (doxycycline group: 5%, p=0.022). Further, the amount of pleural effusion drained on the day after the last chemical pleurodesis in the V. album extract group was greater than that in the doxycycline group (162.2±170.2 mL vs. 97.0±77.2 mL, p=0.032). All patients were discharged from the hospital without complications after pleural effusion drainage. CONCLUSION: Considering that treatment using the V. album extract was less painful, V. album might be a feasible option for chemical pleurodesis. However, pleural effusion should be monitored carefully when using V. album extract for treating patients suffering from air leak.

Acute Respiratory Distress Syndrome after Viscum album Pleurodesis for Primary Spontaneous Pneumothorax

A 52-year-old male patient who underwent multiple wedge resections experienced postoperative acute respiratory distress syndrome in both lungs after Viscum album pleurodesis. Despite initial rapid deterioration in clinical condition and rapid progression of bilateral lung infiltration, he exhibited a relatively smooth clinical recovery with marked response to glucocorticoid treatment. Our case report suggests that care must be taken to guard against the development of acute respiratory complications in the use of Viscum album for pleurodesis. However, in view of the clinically benign course, initial aggressive management of complications can prevent suffering and sequelae.

Korean Mistletoe (Viscum album var. coloratum) Inhibits Amyloid beta Protein (25-35)-induced Cultured Neuronal Cell Damage and Memory Impairment

The present study aims to investigate the effect of methanol extract of Korean mistletoe (KM; Viscum album var. coloratum), on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons and memory impairment in mice. Exposure of cultured neurons to 10 microM Abeta (25-35) for 24 h induced a neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM (10, 30 and 50 microg/ml) significantly inhibited the Abeta (25-35)-induced apoptotic neuronal death. KM (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of intracellular calcium concentration ([Ca2+]i), which was measured by a fluorescent dye, Fluo-4 AM. Glutamate release into medium and generation of reactive oxygen species (ROS) induced by 10 microM Abeta (25-35) were also inhibited by KM (10, 30 and 50 microg/ml). These results suggest that KM may mitigate the Abeta (25-35)-induced neurotoxicity by interfering with the increase of [Ca2+]i and then inhibiting glutamate release and generation of ROS in cultured neurons. In addition, orally administered KM (25 and 50 mg/kg, 7 days) significantly prevented memory impairment induced by intracerebroventricular injection of Abeta (25-35) (8 nmol). Taken together, it is suggested that anti-dementia effect of KM is due to its neuroprotective effect against Abeta (25-35)-induced neurotoxicity and that KM may have therapeutic role in prevention of the progression of Alzheimer's disease.

In vitro Antioxidant Activity of Lectin from Different Endophytic Fungi of Viscum album L.

Objective: To evaluate the antioxidant potential of lectin from the endophytic fungi of Viscum album. Place and duration of study: Department of Biotechnology, Shridevi Institute of Engineering and Technology campus, Tumkur, Karnataka, India between November 2012 and March 2013. Methodology: Isolation, identification of endophytic fungi from Viscum album, mass production, lectin isolation, purification using affinity chromatography. In vitro antioxidant activity of lectin using total antioxidant assay, DPPH, FRAP, Fe3+ reducing assay and H2O2 scavenging activity. Result: Different endophytic fungi were isolated and identified as Aspergillus flavus, Fusarium oxysporum, Fusarium moniliforme, Trichothecium sp. Isolated lectin was capable of agglutinating A+ve erythrocytes, various in vitro antioxidant assays were carried out. Total antioxidant activity showed that (418μg/mg) of ascorbic acid equivalent in the Viscum album extract, among endophyhtes higher activity observed in Fusarium oxysporum (348.54 μg/mg). DPPH assay showed endophytic lectin significantly reduced DPPH free radicals with the low IC50 value observed in Aspergillus flavus (127.9μg/ml) in compared to Viscum album (92.4μg/ml). Highest FRAP value was observed in the location from Viscum album of (180.12μg/ml) among endophytes Aspergillus flavus showed (133.22μg/ml) of the ascorbic acid equivalent of Fe2+/ mg of listing. In Fe3+ reducing ability showed concentration dependent reduction in Fe3+ to Fe2+, low IC50 value was observed in endophytic lectin Fusarium oxysporum (143.4 μg/ml). These values are slightly higher in relation to Viscum album (120.3μg/ml). In H2O2 scavenging activity there was concentration dependent scavenging activity was observed, IC50 value in Fusarium moniliforme was (171.2 μg/ml) , Viscum album is listing showed (183.4 μg/ml). Conclusion: Lectin isolated from endophytic fungi relieved that it was capable of scavenging the free radicals, antioxidant activity was comparatively higher in endophytes than compared with Viscum album. Endophytic lectin could be a novel source for scavenging the free radicals having pharmaceutical value.

Reduction in Serum Bilirubin Concentration Following Administration of Crude Leaf Extract of Viscum album (Mistletoe) in High Salt Fed Rats.

Aims: This study was designed to determine the effect of a high salt diet on serum bilirubin concentration and to ascertain the impact of treatment with Viscum album on same. Methodology: Twenty male albino wistar rats weighing 150 - 200g were used for this study. After seven days of habituation, the animals were randomly divided into four (4) groups of five rats each. Group 1 (NC) served as control and were fed with normal rat pellet and water; group 2(NT) served as the control treated group (administered 150 mg/kg Viscum album orally, in addition to rat pallet and water); group 3 (SF) served as the high salt diet fed group (without treatment), while group 4 (ST) served as the high salt diet fed group, treated orally with 150 mg/kg Viscum album. The feeding regimen lasted for six weeks, after which the animals were sacrificed and blood samples collected for analysis. Results: Mean serum total bilirubin concentration was significantly (p<0.001) higher in the SF group compared to control, NT and ST group. It was also significantly (p<0.001) lower in the ST group compared to SF group. Serum conjugated bilirubin concentration was significantly (p<0.001) increased in the SF group compared to NC, NT and ST group. It was also significantly (p<0.001) reduced in the ST group compared to the SF group. Serum unconjugated bilirubin concentration was significantly (p<0.001) increased in the SF group compared to NC, NT and ST group. Serum unconjugated bilirubin concentration was significantly (p<0.01) lower in the ST group compared to SF group. Conclusion: Our results are indicative of the fact that oral administration of Viscum album reduces serum bilirubin concentration in high salt fed animals.

Comparative Effects of Aloe vera Gel and Aqueous Leaf Extract of Viscum album on Bilirubin Excretion in Streptozotocin - Induced Diabetic Rats.

This study was carried out to determine the effect of type 1 Diabetes Mellitus on bilirubin excretion and to compare the effects of separate administration of Aloe vera gel and aqueous leaf extract of Viscum album on serum bilirubin, bile secretory rate and biliary bilirubin concentration. Methodology: Thirty six male albino Wistar rats weighing 180 - 220 g were used for this study. After 14 days of habituation, the rats were randomly divided into 6 groups of 6 rats each. Type 1 Diabetes Mellitus was induced in the test groups by a single i.p dose (65 mg/kg) of streptozotocin. Group 1 served as control; group 2 - diabetic untreated group (DM); group 3 - diabetic group, treated with 0.4 ml/100g Aloe vera gel orally (DM+Aloe); group 4 - diabetic group, treated with 150 mg/kg Viscum album leaf extract orally (DM+VA); group 5 - control group, treated with 0.4 ml/100g Aloe vera gel orally (C+Aloe); group 6 - control group, treated with 150 mg/kg Viscum album leaf extract orally (C+VA). All animals had unrestricted access to food and water. The regimen lasted for 21 days, after which bile secretion was determined and same was collected together with serum for biliary and serum bilirubin estimation. Results: The results showed that serum and biliary total, conjugated and unconjugated bilirubin concentrations were significantly (p<0.001) higher in the DM group compared to control, DM+Aloe and DM+VA, with DM+Aloe group having significantly lower serum and biliary total and conjugated bilirubin (p<0.001), and serum unconjugated bilirubin (p<0.05) compared to DM+VA group. Serum conjugated bilirubin concentration in C+Aloe and C+VA group was significantly (p<0.05 and p<0.001 respectively) higher compared to control, while serum unconjugated bilirubin concentration was significantly (p<0.001 and p<0.01 respectively) lower compared to control. C+VA group had a significantly (p<0.001) higher biliary total and conjugated bilirubin concentrations compared to C+Aloe group. Conclusion: On the basis of the results obtained, we therefore conclude that Aloe vera gel and aqueous leaf extract of Viscum album enhances bilirubin excretion in diabetic and normal animals and are both hepatoprotective.

Ação do Viscum album em cultivo celular de carcinoma epidermoide de cabeça e pescoço / Viscum album effect in head and neck squamous cell carcinoma cell culture

O carcinoma epidermoide de cabeça e pescoço, hoje considerada mundialmente uma das neoplasias mais frequentes desta região, tornou-se um problema de saúde pública, necessitando urgente de medidas a serem tomadas, a fim de melhorar a qualidade de vida dos pacientes acometidos, consequentemente aumentando a sobrevida, avaliada em cinco anos. O carcinoma epidermoide de cabeça e pescoço é uma doença complexa, e inclui vários fatores etiológicos, além de alterações moleculares, capazes de desencadear e dar continuidade a alguns eventos. No geral os carcinomas orais são tratados primeiramente com cirurgia excisional ou radioterapia individualmente, ou em combinação para os estágios mais avançados. As preparações dos extratos fermentados de Viscum album (VA), uma planta semiparasita da família das Lorantáceas, vêm sendo utilizada, principalmente em países da Europa, com resultados promissores no âmbito das terapias coadjuvantes, especialmente a medicina antroposófica. Em conjunto com as terapias convencionais, tem demonstrado uma melhora na qualidade de vida dos pacientes portadores de neoplasias malígnas. Estudos in vitro, realizados em células cancerígenas, têm demonstrado que vários tipos de VA podem apresentar citotoxicidade em células de carcinoma, sendo capazes de ativar a cascata apoptótica ou levando as células à necrose. Este estudo teve por objetivo verificar a ação de três tipos de extratos de VA (Iscador Qu Spezial, Iscador P e Iscador M), em linhagens celulares de carcinoma epidermoide de língua (SCC9 e SCC25). Para isso foi verificada a ação citotóxica do fármaco Iscador Qu Spezial, por meio do teste de viabilidade celular, para a obtenção da IC50...

Head and neck squamous cell carcinoma, one of the most common malignancies worldwide in this area, became a public health problem that requires urgent attitudes to be taken in order to improve the quality of life of the affected patients, increasing survival that today valued at five years. Head and neck squamous cell carcinoma is a complex disease which includes several etiologic factors and different molecular changes that may trigger and get on with some events. In general, oral carcinomas are treated primarily with surgical excision or radiotherapy alone or in combination for cases in more advanced stages. Preparations of fermented extracts from fermented Viscum album (VA), a plant from the Loranthaceae family have been used, mainly in European countries, with promising results as adjuvant therapies, especially in the Anthroposophy Medicine. In combination with conventional therapies, VA has lead to improvement in quality of life of patients with cancer. in vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells being able to activate the apoptotic cascade or leading cells to necrosis. The present study aimed to verify the effect of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue (SCC9 and SCC25). The cytotoxic action of Iscador Qu Spezial was verified by cell viability test obtaining the IC50. The three drugs were tested as follow: Tunnel to evaluate apoptosis, Annexin V and FITC/propidium iodide were evaluated by flow cytometry to quantify the apoptosis rate induced by the drugs...

Immumoadjuvant Activitiy of Korean Mistletoe Extract ( Viscum album coloratum ) to Enhance Humoral and Cellular Immune Response / 대한면역학회지

Immunoadjuvant activities of the extract (KM-110) from Korean mistletoe ( Viscum album coloratum) on the induction of humoral and cellular responses against Keyhole limpet hemocyanim (KLH) as an antigen and allogenic tumor cells were examined. When mice were immunized subcataneously (s.c.) with KLH admixed with KM-110, more than 1000-times higher antibody titers to KLH than those immunized with KLH alone was observed. KM-110 induced high level of KLH- specific IgG1, IgG2a and IgG2b antibodies. In an in vitro analysis of lymphocytes proliferation to KLH on week 4, the splenocytes of mice treated with KLH and KM- 110 exhibited significantly higher proliferating activity than those treated with KLH alone. In addition, the culture supernatnats obtained from the splenocytes of mice treated with both KLH and KM-110 showed high level of IL-2 and IL-4. In the test of cellular immune responses, KM-110 enhanced the DTH reaction to KLH in mice. Furthemore, cytotoxic T-lymphocyte (CTL) activity using an allogenic CTL induction model where C57BL/6 (H-2b) mice were injected with allogenic P815 (H-2d) mastocytoma cells admixed with or without KM-110, mice treated with P815 cells and KM-110 showed higher cytatoxic activity against allogenic tumor cells than those treated without KM-110. This results suggest that KM-110 may possess adjuvant activities to potentially enhance humoral as well as cellular immune responses against antigens.

Immunological Activities of Korean Mistletoe Extract ( Viscum album coloratum ; KM - 110 ) / 대한면역학회지

Immunological effect of the extract (KM-110) from Korean mistletoe (Viscum album coloratum) was examined. Lymphocytes obtained from KM-110-administrated mice showed increased responsiveness to mitogens, concanavalin-A (Con.A) and lipopolysaccharide (LPS). In order to study cytokine induct ability of the KM-110, macrophages from the Balb/c mice were cultivated in the medium containing the extract. the macrophages were shown to induce secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 and 6 (IL-1, IL-6) and interferon-gamma (INF-gamma). We then tested antitumor activity of the macrophages activated by the KM-110. Peritoneal macrophages harvested from the KM110-treated Balb/c mice exhibited cytotoxicity against the syngeneic 3LL carcinoma cells. ...continue...