ChiroACCESS Article

Mistletoe for Kissing & Health

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ChiroACCESS Editorial Staff



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December 27, 2011

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There is controversy over the origins of the tradition of kissing under mistletoe at Christmas and similar controversies extend to the use of mistletoe to promote human health. A review of research published the past two years has added a great deal to an understanding of the science related to the therapeutic effects of mistletoe lectins and other plant derivatives. This new research suggests that there are fewer risks of adverse effects from mistletoe lectin treatment than previously believed. Numerous studies support the role of mistletoe therapy with both improvement of quality of life and potentially inhibiting tumor growth in patients with multiple forms of cancer. In fact, most of the studies this last year have focused on the cancer issue elucidating some of the underlying mechanisms by which mistletoe may have an impact in cancer care. Although individual patient case reports do not provide evidence of cause and effect, an interesting case was published of a 43 year old woman with pancreatic adenocarcinoma that had spread to the lymph system and liver. After surgery she was given chemotherapy and began taking mistletoe abstracts. Ten months later the cancer was in remission and the authors point out that “…long term remission of metastatic pancreatic cancer are extremely rare.” Like this case report, much of the therapeutic benefits ascribed to mistletoe are largely unsubstantiated but we are beginning to know more.

This is our second article on mistletoe. The first appeared in December 2009. To read more you will find that article here.

Note:  These mini-reviews are designed as updates and direct the reader to the full text of current research.  The abstracts presented here are no substitute for reading and critically reviewing the full text of the original research.  Where permitted we will direct the reader to that full text.

Safety and effects of two mistletoe preparations on production of Interleukin-6 and other immune parameters - a placebo controlled clinical trial in healthy subjects.  [Link]

BMC Complement Altern Med. 2011 Nov 24;11(1):116. [Epub ahead of print]

Huber R, Ludtke H, Wieber J, Beckmann C.

BACKGROUND: In Germany, Iscucin(R) Populi (IP), a preparation from mistletoe growing on the poplar tree, is used in cancer therapy while Viscum Mali e planta tota (VM), a preparation from mistletoe growing on the apple tree, is used in patients with osteoarthritis. Since mistletoe preparations are suspected to induce production of potentially tumor promoting cytokines like interleukin (IL)-6, further studies on the immunological effects are of interest.

METHODS: In this 3-armed randomized, double blind clinical trial healthy volunteers received increasing doses of either IP (strength F, 0.0125%, G, 0.25% and H, 5%, each for 4 weeks), or VM (1:1000 [D3], 1:100 [D2] and 2% each for 4 weeks) or placebo (isotonic solution) subcutaneously twice per week over a period of 12 weeks. Physical examination was performed weekly. Routine laboratory parameters and immunological parameters (C-reactive protein (CRP), differential blood count, lymphocyte subsets, immunoglobulins, IL-6 and tumor necrosis factor (TNF)-alpha) were analysed every 4 weeks.

RESULTS: 71 subjects were included in the study (IP=30, VM=21, placebo=20) of whom 69 concluded it according to protocol. Application of IP strengths G and H caused strong local reactions at the site of injection. In parallel, a distinct eosinophilia (p<0.001 compared to placebo) occurred. Furthermore, application of all IP concentrations resulted in an increase of CD4 cell counts (p<0.05) compared to placebo. Stimulation of IL-6 production, CRP or relevant deviations in other laboratory parameters were not observed. Because of local reactions, IP strengths G and H were considered less tolerable than placebo. VM 2% was slightly less tolerable than placebo, caused only mild local reactions and an only small increase in eosinophile counts.

CONCLUSION: Treatment with IP results in eosinophilia and an increase of CD4 cells but not in an increase of IL-6 or CRP. No safety concerns regarding the two mistletoe preparations have been raised by this study.

EudraCT-Number 2007-002166-35. Trial registration: NCT01378702.

Case reports of sarcoma patients with optimized lectin-oriented mistletoe extract therapy.  [Link]

J Altern Complement Med. 2011 Oct;17(10):973-9.

Kirsch A, Hajto T.
Department of Immunology and Biotechnology, University of Pècs, Faculty of Medicine, Pècs, Hungary.

BACKGROUND: Mistletoe (Viscum album L) extracts (ME) are widespread as immunomodulatory therapeutic agents in alternative tumor treatment. Assessing the often-controversial clinical results is rather difficult since the effects of ME on the immune system cannot be equally reproduced. Mistletoe lectins (ML) are the only mistletoe ingredients also found in vivo that are capable of having a positive effect on the immune balance of patients with tumors. Other components have only been tested in vitro, and the removal of mistletoe lectins ML from the extract can put an end to the immunological efficacy of ME. Preclinical investigations in the tumor models (using nude mice xenotransplanted with human leiomyosarcoma and interleukin-12-deficient C57BL6 mice) show that without immunological reactions, ME induce less antitumor efficacy. ML, functioning as ligands for pattern recognition receptors of the natural immune system, are docked to ganglioside molecules (CD75) of monocytes and granulocytes, thereby stimulating the natural antitumor mechanisms.

OBJECTIVES: The aim of this article is to present and discuss several favorable clinical responses of patients who had sarcoma and who were treated with immunologically effective ME preparations.

COURSE OF THERAPY AND RESULTS: In accordance with the bell-shaped dose-response relationship of ML, the patients with sarcoma were treated with ME preparations, standardized for the active sugar-binding lectin contents. Thus, an optimal dose of 0.75-1.0 ng/kg ML was given twice a week subcutaneously. In this report, the clinical progress of 6 patients with sarcoma showed remissions of tumor symptoms.

CONCLUSIONS: It seems that this disease is beneficially influenced by optimized lectin-oriented ME therapy since patients with sarcoma may react especially well to the improved balance of natural immunological mechanisms. These case reports require further clinical studies with patients with sarcoma.

Safety of higher dosages of Viscum album L. in animals and humans--systematic review of immune changes and safety parameters.  [Link]

BMC Complement Altern Med. 2011 Aug 28;11:72.

Kienle GS, Grugel R, Kiene H.
Institute for Applied Epistemology and Medical Methodology, University of Witten/Herdecke, Zechenweg 6, 79111 Freiburg, Germany.

BACKGROUND: Viscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects.

METHODS: Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions.

RESULTS: 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 µg/kg in humans and in animals up to 14 µg/kg subcutaneously, 50 µg/kg nasally and 500 µg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases.

CONCLUSIONS: Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

Plant lectins: targeting programmed cell death pathways as antitumor agents.  [Link]

Int J Biochem Cell Biol. 2011 Oct;43(10):1442-9. Epub 2011 Jul 20.

Fu LL, Zhou CC, Yao S, Yu JY, Liu B, Bao JK.
School of Life Sciences & State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

Lectins, a group of highly diverse, carbohydrate-binding proteins of non-immune origin that are ubiquitously distributed in plants, animals and fungi, are well-characterized to have numerous links a wide range of pathological processes, most notably cancer. In this review, we present a brief outline of the representative plant lectins including Ricin-B family, proteins with legume lectin domains and GNA family that can induce cancer cell death via targeting programmed cell death pathways. Amongst these above-mentioned lectins, we demonstrate that mistletoe lectins (MLs), Ricin, Concanavalin A (ConA) and Polygonatum cyrtonema lectin (PCL) can lead to cancer cell programmed death via targeting apoptotic pathways. In addition, we show that ConA and PCL can also result in cancer cell programmed death by targeting autophagic pathways. Moreover, we summarize the possible anti-cancer therapeutic implications of plant lectins such as ConA, Phaseolus vulgaris lectin (PHA) and MLs that have been utilized at different stages of preclinical and clinical trials. Together, these findings can provide a comprehensive perspective for further elucidating the roles of plant lectins that may target programmed cell death pathways in cancer pathogenesis and therapeutics. And, this research may, in turn, ultimately help cancer biologists and clinicians to exploit lectins as potential novel antitumor drugs in the future.

An Exploratory Study on the Quality of Life and Individual Coping of Cancer Patients During Mistletoe Therapy.  [Link]

Integr Cancer Ther. 2011 Jul 6. [Epub ahead of print]

Brandenberger M, Simões-Wüst AP, Rostock M, Rist L, Saller R.
Paracelsus Hospital Richterswil, Richterswil, Switzerland.

BACKGROUND: Although several clinical studies have shown that mistletoe therapy (MT, Viscum album) may improve cancer patients' quality-of-life (QoL), qualitative information on the improvement's nature is still lacking. Design. This exploratory, prospective, cohort-study comprised 25 patients with different types of cancer. The patients filled in the EORTC QLQ-C30 Version 3.0 questionnaire at the beginning of MT (n = 25) and three months later (n = 21). If patients agreed, they were interviewed on both occasions (n = 17); the interviews were transcribed verbatim and submitted to a qualitative content analysis (n = 12).

RESULTS: Analysis of the questionnaires showed significant improvements in several subscales during MT. The interviews analysis revealed that most patients adopted the MT with a supportive goal, with all patients undergoing conventional therapies. After three months of MT, most interviewed patients revealed higher vitality and autonomy. MT was often seen as a chance to make an own personal contribution to the therapy, which was particularly appreciated in cases in which no conventional therapy was (anymore) advised. Concrete personal achievements such as changes in the private and/or in the professional environment were spontaneously mentioned by the patients, illustrating and corroborating their improvements in QoL.

CONCLUSION: Our results show that the patients experienced an improvement of QoL during MT. This therapy seemed to offer a platform for an integrative coping with the disease, which might be important in reconciling the perceived shock of an existential illness with a good QoL.

Targeting the oncogenic role of miRNA in human cancer using naturally occurring compounds.  [Link]

Br J Pharmacol. 2011 Jan;162(2):346-8.

Rushworth SA.
University of East Anglia, Norwich, UK.

Micro-RNAs (miRNAs) are small RNA molecules that regulate the expression of genes involved in development, growth, proliferation and apoptosis. In cancer several miRNAs have been functionally classified as oncogenes or tumour suppressers or act to regulate transcription factors, like nuclear factor kappa B and NF-E2–related factor 2, in cancers such as leukaemia, breast and colorectal. Therefore, it has been proposed that manipulating miRNA regulation may be a novel avenue for developing efficient therapies against cancer. In this issue, Li and colleagues describe a novel way of targeting miRNA, by using a naturally occurring anti-cancer compound found in mistletoe which they showed to down-regulate miR-135a&b, which target the 3' untranslated region of adenomatous polyposis coli gene, the inactivation of which is a major initiating event in colorectal tumourigenesis. This commentary aims to discuss the regulatory mechanisms of miRNA synthesis and the potential outcomes for using naturally occurring compounds antioxidants or cellular antioxidant pathways to target miRNA for therapeutic intervention.

Sustained partial remission of metastatic pancreatic cancer following systemic chemotherapy with gemcitabine and oxaliplatin plus adjunctive treatment with mistletoe extract.  [Link]

Onkologie. 2010;33(11):617-9. Epub 2010 Oct 19.

Ritter PR, Tischoff I, Uhl W, Schmidt WE, Meier JJ.
Department of Medicine I, St. Josef Hospital, Ruhr-University Bochum, Germany.

BACKGROUND: The clinical prognosis of metastatic pancreatic cancer is very poor, with a median survival time of such patients ranging from 3 to 6 months. Current chemotherapy regimens include the combination of oxaliplatin and gemcitabine.

CASE REPORT: A 43-year-old woman was diagnosed with pancreatic adenocarcinoma spreading into the regional lymph nodes and into multiple liver segments (pT3, pN1, pM1). Upon diagnosis, she underwent a pylorus-preserving pancreatic head resection, including dissection of regional lymph nodes and atypical resection of a single liver segment, followed by 9 cycles of palliative chemotherapy with gemcitabine and oxaliplatin. 37 weeks after surgery, the patient demonstrated a sustained partial remission, and the chemotherapy was stopped. Surprisingly, 10 months later, she still showed no evidence of tumor progression. Since the time of pancreatic surgery, the patient had taken mistletoe extracts and this adjunctive treatment has been continued until now.

CONCLUSIONS: Cases of sustained long-term remission of metastatic pancreatic cancer are extremely rare. Although this single case observation does not allow for firm conclusions regarding potential mechanisms, the adjunctive therapy with mistletoe extracts might have played a role. Therefore, the clinical effects of such treatment in patients with pancreatic cancer warrant further investigation.

Down-regulation of some miRNAs by degrading their precursors contributes to anti-cancer effect of mistletoe lectin-I.  [Link]

Br J Pharmacol. 2011 Jan;162(2):349-64.

Li LN, Zhang HD, Zhi R, Yuan SJ.
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, China.

BACKGROUND AND PURPOSE: Mistletoe lectin-I (ML-I), the main anti-cancer component of mistletoe extracts, was originally thought to act exclusively on 28S rRNA. Here, we investigate the down-regulating effect and mechanism of CM-1, an ML-I isolated from Chinese mistletoe, on some miRNAs.

EXPERIMENTAL APPROACH: The anti-cancer effects of CM-1 were assessed in vitro and in vivo in colorectal cancer cells. The miRNAs down-regulated by CM-1 were identified by miRNA microarray assay and validated by qRT-PCR analysis. The suppression of host gene transcription or by degradation of precursors was determined by qRT-PCR and enzyme activity assays respectively. The qRT-PCR, Western blot and immunohistochemistry were used to examine the expression of their target gene and related downstream effector. Cell proliferation was assayed in stably transfected HEK-293 cells with different levels of these miRNAs.

KEY RESULTS: CM-1 showed prominent anti-neoplastic activity towards CLY and HT-29 cells both in vitro and in vivo. The miR-135a&b were the miRNAs most down-regulated by CM-1. Their host gene transcription was largely up-regulated, while their precursors were degraded directly by CM-1. The expression of their target gene adenomatous polyposis coli and the phosphorylation of related effector ß-catenin were both significantly up-regulated. The IC(50) values of CM-1 on derivative HEK-293 cells with high miR-135a&b levels were 2-4 times lower than that of control cells.

CONCLUSIONS AND IMPLICATIONS: CM-1 down-regulated some miRNAs by degrading their precursors, which contributes to its prominent anti-cancer activity.

Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract.  [Link]

Phytomedicine. 2011 Jan 15;18(2-3):151-7. Epub 2010 Aug 19.

Eisenbraun J, Scheer R, Kröz M, Schad F, Huber R.
ABNOBA GmbH, Hohenzollernstr. 16, D-75177 Pforzheim, Germany.

BACKGROUND: The effects of standardized aqueous mistletoe extracts on Health Related Quality of Life (HRQoL) of tumor patients needs further evaluation.

METHODS: in this non-interventional, prospective clinical investigation the longitudinal course of Quality of Life of 270 breast cancer patients during adjuvant chemotherapy and mistletoe therapy with abnobaVISCUM(®) Mali was investigated. HRQoL was measured 4 times by self-assessment with the QLQ-C30 and QLQ-BR23 questionnaire of the European Organization for Research and Treatment of Cancer (EORTC): at the beginning of mistletoe- and chemotherapy, 4 weeks later, at the end of the chemotherapy and 4 weeks after finishing chemotherapy. Secondary objectives were the tolerability and safety of mistletoe therapy in combination with chemotherapy under conditions of daily practice.

RESULTS: after an initial deterioration the average range of all obtained QLQ-C30 function scales (n=262, 48.9-71.5) remained stable even at the last chemotherapy cycle and improved significantly (p<0.0001) to 66.9-80.7 4 weeks later, compared to the initial visit. Also the QLQ-BR23 function scales significantly improved (p<0.0001) 4 weeks later. The symptom scales of the QLQ-C30 remained stable under chemotherapy even at the final chemotherapy cycle and decreased from 16.2 to 44.1 at the initial visit to 11.2-29.9 (p<0.001) at the final visit. These results were comparable to the subgroup with initial visit before chemotherapy (n=114) in which rather stable function scales during chemotherapy (difference of the mean values: 9.6 to -3.7) and only little increase of symptoms (difference: 13.2 to -4.9) was measured. The tolerability of the therapy was judged by the physicians as good or very good for 91% of the patients and the efficacy was rated as good or very good for 94%. 89% of the patients reported about a good or very good benefit.

CONCLUSION: the overall results point to a relevant stabilisation of Health Related Quality of Life during various chemotherapy regimes, possibly due to a reduction of chemotherapy caused side effects with an excellent tolerability of the mistletoe therapy.

Antibodies raised against tobacco aquaporins of the PIP2 class label viscin tissue of the explosive dwarf mistletoe fruit.  [Link]

Plant Biol (Stuttg). 2010 Jan;12(1):229-33.

Ross Friedman CM, Ross BN, Martens GD.
Department of Biological Sciences, Thompson Rivers University, Kamloops, BC, Canada.

Dwarf mistletoes, genus Arceuthobium, are parasitic flowering plants and forest pests. In western North America, Arceuthobium americanum (lodgepole pine dwarf mistletoe) is principally found on Pinus contorta var. latifolia (lodgepole pine). Dwarf mistletoes disperse their seeds by an explosive process that involves the buildup of hydrostatic pressure within a mucilaginous fruit tissue called the 'viscin'. Living viscin tissue envelops the discharged seeds. This study examined the possibility that aquaporins, critical in plant water relations, might be found in the dwarf mistletoe fruit, specifically the viscin cells. An antibody raised against a tobacco plasma membrane intrinsic 2 (PIP2) aquaporin was used with a gold-labeled secondary antibody to probe dwarf mistletoe fruit at various developmental stages. Viscin cell plasma membranes were successfully labeled with the anti-tobacco probe, and the validity of the immunolabeling was supported by Western blot analysis, showing a strong signal at about 30 kDa, which is at the expected size of a PIP2. A definitive immunolabeling pattern, supported by quantification of gold signal per membrane length, was observed: viscin cells sampled early in development had abundant gold label at their plasma membranes (1.93 +/- 0.13 to 2.13 +/- 0.33 gold particles per microm membrane), while other areas of the cells had no discernible label. Viscin cells sampled near the time of explosive discharge had significantly less label at the plasma membrane (0.21 gold particles +/- 0.11 per microm membrane, P < 0.05), and label was seen at vesicular membranes. Aquaporins likely have a role in directing water to the viscin mucilage early in development, but are retrieved via endocytosis to prevent excess water loss from viscin cells when discharge is imminent.

Diuretic activity of squamate mistletoe, Viscum angulatum.  [Link]

Pharm Biol. 2010 Apr;48(4):417-21.

Jadhav RB, Bhatnagar SP, Surana SJ.
Bioecology Laboratory, Department of Pharmacognosy, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.

Viscum angulatum Heyne ex DC (Viscaceae) is a leafless hemiparasitic shrub traditionally used in Asian countries for the treatment of hypertension. In the present study, the methanol extract of the whole plant was examined for diuretic activity in rats. The activity was evaluated using parameters such as urine volume after 5, 19, and 24 h and urine sodium, potassium, and chloride concentrations. The extract was further scrutinized for polyphenolic compounds and triterpenoids. The extract demonstrated a significant increase in and dose-dependent effect on urine excretion volume in comparison to the normal group in the tested range of 100-400 mg/kg. The extract demonstrated comparable saluretic and higher natriuretic activity (Na(+)/K(+)) compared to the furosemide treated group. However, the Cl(-)/Na(+) + K(+) ratio, which indicates carbonic anhydrase mediated activity, remained unaffected. HPLC and quantitative analysis of the extract revealed that polyphenolic compounds and the triterpenoid, oleanolic acid, are the major phytochemicals, and are proposed to be responsible for the observed diuretic effect. Oleanolic acid has been reported to possess diuretic activity with significant potassium loss in rats. In contrast to pure oleanolic acid, the extract demonstrated a valuable potassium-sparing effect. This suggests modulation of the diuretic effect of oleanolic acid by polyphenolics present in the extract. The observed dose-dependent potassium-sparing diuretic effect is a hereto unreported property of this plant.

Protective effects of Korean mistletoe lectin on radical-induced oxidative stress.  [Link]

Biol Pharm Bull. 2010;33(7):1152-8.

Kim BK, Choi MJ, Park KY, Cho EJ.
Department of Food Science and Nutrition, Pusan National University, Busan, Korea.

The radical scavenging effects and protective activities against oxidative stress of Korean mistletoe (Viscum album coloratum) lectin were investigated in vitro and with a cellular system using LLC-PK(1) renal epithelial cells. The Korean mistletoe lectin (KML) showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity with an IC(50) value of 42.6 microg/ml. It also exerted nitric oxide (NO), superoxide anion (O(2)(-)), and hydroxyl radical scavenging activities in concentration-dependent manners. These results suggest that KML is a promising antioxidant by scavenging free radicals. Furthermore, under the LLC-PK(1) cellular model, the cells showed declines in viability and increases in lipid peroxidation through oxidative stress induced by sodium nitroprusside (SNP) and pyrogallol, generators of NO and O(2)(-), respectively. However, KML significantly and dose-dependently inhibited cell cytotoxicity and lipid peroxidation. In addition, 3-morpholinosydnonimnie (SIN-1), a generator of peroxynitrite (ONOO(-)) formed by simultaneously releases of NO and O(2)(-), caused cytotoxicity, lipid peroxidation, and NO overproduction in the LLC-PK(1) cells while KML ameliorated ONOO(-)-induced oxidative damage. Furthermore, overexpressions of cyclooxygenase-2 and inducible NO synthase induced by SIN-1 were observed, but KML down-regulated the expression levels of both genes. KML also reduced SIN-1-induced nuclear factor kappa B expression and the phosphorylation of inhibitor kappa B alpha in LLC-PK(1) cells. These results indicate that KML has protective activities against oxidative damage induced by free radicals.

Free radical scavenging activities and inhibition of inflammatory enzymes of phenolics isolated from Tripodanthus acutifolius  [Link]

J Ethnopharmacol. 2010 Jul 20;130(2):329-33. Epub 2010 May 19.

Soberón JR, Sgariglia MA, Sampietro DA, Quiroga EN, Vattuone MA.
Instituto de Estudios Vegetales Dr. A.R. Sampietro, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, San Miguel de Tucumán, Tucumán, Argentina.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaf extracts from Tripodanthus acutifolius (Ruiz and Pavón) Van Tieghem have long been used in Argentinean traditional medicine as anti-inflammatory, however, there is no scientific evidence which supports this use in the literature.

AIM OF THE STUDY: The present study was conducted to evaluate the ability of five phenolic compounds purified from infusion prepared from Tripodanthus acutifolius leaves to inhibit key enzymes in inflammatory processes. As anti-inflammatory compounds frequently possess free radical scavenging activities, purified substances were comparatively evaluated to asses their free radical scavenging properties. Genotoxic effects were also evaluated.

MATERIALS AND METHODS: Compounds were evaluated on their ability to inhibit hyaluronidase and cyclooxygenase-2 (COX-2) activities to assess their anti-inflammatory capacities. Free radical scavenging activity was assessed by: 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH), superoxide anion assay and the inhibition on lipid peroxidation. Genotoxicity was evaluated by Bacillus subtilis rec assay.

RESULTS: Fractionation of Tripodanthus acutifolius infusion yielded a novel phenylbutanoid derivative (tripodantoside) and four known flavonoid glycosides (rutin, nicotiflorin, hyperoside and isoquercitrin). Flavonoids produced higher inhibition on hyluronidase activity (IC(50) approximately 1.7 mM) than tripodantoside (IC(50)=27.90 mM). A similar COX-2 inhibition activity was exerted by tripodantoside and monoglycosilated flavonoids (IC(50) approximately 50 microM). Compounds were strong radical scavengers, with effective concentration 50 (EC(50)) values for DPPH in the range of 2.7-6.3 microg/mL, and for superoxide anion in the range of 3.9-8.7 microg/mL. All compounds scavenged peroxyl radicals in the lipid peroxidation assay. The substances showed no genotoxic effects.

CONCLUSIONS: The anti-inflammatory effects, free radical scavenging activities and lack of genotoxicity of purified compounds may support the folk use of infusion from Tripodanthus acutifolius leaves as anti-inflammatory.

Immunomodulatory effects of Viscum album extracts on natural killer cells: review of clinical trials.  [Link]

Forsch Komplementmed. 2010 Apr;17(2):63-73. Epub 2010 Mar 12.

Braedel-Ruoff S.
Braedel Scientific Consulting, Droste-Hülshoff-Weg 35, 73431 Aalen, Germany.

Extracts produced from Viscum album L. (mistletoe) are widely used in complementary medicine for the treatment of cancer. In many preclinical and clinical studies, Viscum album extracts were shown to exert immunomodulatory functions. Natural killer (NK) cells play an important role in cell-mediated immune responses against tumor cells. This article reviews clinical trials that address the influence of the mistletoe extract Iscador on NK cells and discusses the results with regard to the NK cell functions assayed, to putative underlying mechanisms, and to the role of different mistletoe components. Conclusion: Although many trials demonstrated a positive effect of Iscador treatment on NK cell function, further dedicated studies with optimized treatment schedules and comparable mistletoe doses are necessary to confirm these results regarding involvement of NK cells on the immunomodulatory functions of Iscador therapy and to investigate the clinical relevance of these findings.

Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies.  [Link]

Integr Cancer Ther. 2010 Jun;9(2):142-57. Epub 2010 May 18.

Kienle GS, Kiene H.
Institute for Applied Epistemology and Medical Methodology, Zechenweg 6, Freiburg, Germany.

OBJECTIVE: To evaluate controlled clinical studies on the efficacy and effectiveness of Viscum album for quality of life (QoL) in cancer.

MATERIALS AND METHODS: The authors conducted a search of 7 electronic databases and reference lists and had extensive consultations with experts. They carried out a criteria-based assessment of methodological study quality.

RESULTS: The authors identified 26 randomized controlled trials (RCTs) and 10 non-RCTs that investigated the influence of V album extracts (VAEs) on QoL in malignant diseases; 26 studies assessed patient-reported QoL. Questionnaires were mostly well established and validated. Half of the studies investigated VAEs concomitant with chemotherapy, radiotherapy, or surgery. Some studies were well designed, whereas others had minor or major methodological weaknesses. Among the 26 RCTs, 22 reported a QoL benefit, 3 indicated no difference, and 1 did not report any result. All the non-RCTs reported a QoL benefit. Of the studies with higher methodological quality, most reported a benefit, whereas 1 found no difference. Improvements were mainly in regard to coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being in general and, less consistently, in regard to pain, diarrhea, general performance, and side effects of conventional treatments. VAEs were well tolerated.

CONCLUSIONS: VAEs seem to have an impact on QoL and reduction of side effects of conventional therapies (chemotherapy, radiation) in experimental trials as well as in routine daily application. The influence on fatigue especially should be investigated further.

Study on the mechanism of compound mistletoe fluidextract in relieving hypertension.  [Link]

J Tradit Chin Med. 2009 Dec;29(4):291-5.

Ye F, Du GZ, Cui AQ, Lu XT.
Qilu Hospital of Shandong University, Jinan 250012, China.

OBJECTIVE: To observe the effect of fufang jisheng liujin gao (Compound Mistletoe Fluidextract) on blood pressure in the spontaneous hypertensive rats (SHR) and the renal hypertensive dogs (RHD).

METHODS: The blood pressure-decreasing effects of single administration and 14-day consecutive administration of Compound Mistletoe Fluidextract (CMF) in SHR and RHD were investigated and compared with that of niuhuang jiangya wan (Bezoar Hypertension-relieving Pills).

RESULTS: Both single administration and 14-day consecutive administration of CMF had significant hypotensive effects in SHR and RHD.

CONCLUSION: The hypotensive action of CMF is gradual, but lasts for a longer period, with a dose-effect relationship in a range of doses.
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