Mistletoe Extract Research Articles

Immuno-Modulatory Effects of Korean Mistletoe in MDA-MB-231 Breast Cancer Cells and THP-1 Macrophages

Korean mistletoe (Viscum album var. coloratum) has been traditionally used as a remedy for cancer, diabetes, and hypertension. This study investigated the immuno-modulatory effects of Korean mistletoe water extract, specifically on MDA-MB-231 cells, a highly metastatic breast cancer cell line, when co-cultured with THP-1 human macrophage cells. When compared to MDA-MB-231 cells cultured alone, the co-culture of MDA-MB-231/THP-1 cells treated with mistletoe extract showed a significant reduction in IL-6 secretion. Additionally, these co-cultures exhibited elevated levels of IL-4, TGF-β, and IFN-y. These results suggest that water extracts from mistletoe have the potential to induce mitochondria-targeted apoptosis in MDA-MB 231 cells stimulated by THP macrophages. Regarding apoptosis, in MDA-MB-231 cells co-cultured with THP-1 macrophages, mistletoe water extract treatment triggered a significant increase in Bax/Bcl-2 ratio, caspase-3 activation, and PARP inactivation. In addition, there was a significant increase in E-cadherin and a decrease in N-cadherin. Treatment of Korean mistletoe also led to significant reductions in both MMP-2 and -9. Furthermore, inhibition of cell migration in MDA-MB-231/THP-1 co-cultured cells was observed. In summary, this study highlights the potential of Korean mistletoe as a prospective drug for the treatment of triple-negative breast cancer, particularly through its ability to regulate human immunity.

Mistletoe Extracts from Different Host Trees Disparately Inhibit Bladder Cancer Cell Growth and Proliferation.

Extracts of European mistletoe (Viscum album) are popular as a complementary treatment for patients with many different cancer types. However, whether these extracts actually block bladder cancer progression remains unknown. The influence of different mistletoe extracts on bladder cancer cell growth and proliferation was investigated by exposing RT112, UMUC3, and TCCSup cells to mistletoe from hawthorn (Crataegi), lime trees (Tiliae), willow trees (Salicis), or poplar trees (Populi). The tumor cell growth and proliferation, apoptosis induction, and cell cycle progression were then evaluated. Alterations in integrin α and β subtype expression as well as CD44 standard (CD44s) and CD44 variant (CD44v) expressions were evaluated. Cell cycle-regulating proteins (CDK1 and 2, Cyclin A and B) were also investigated. Blocking and knock-down studies served to correlate protein alterations with cell growth. All extracts significantly down-regulated the growth and proliferation of all bladder cancer cell lines, most strongly in RT112 and UMUC3 cells. Alterations in CD44 expression were not homogeneous but rather depended on the extract and the cell line. Integrin α3 was, likewise, differently modified. Integrin α5 was diminished in RT112 and UMUC3 cells (significantly) and TCCSup (trend) by Populi and Salicis. Populi and Salicis arrested UMUC3 in G0/G1 to a similar extent, whereas apoptosis was induced most efficiently by Salicis. Examination of cell cycle-regulating proteins revealed down-regulation of CDK1 and 2 and Cyclin A by Salicis but down-regulation of CDK2 and Cyclin A by Populi. Blocking and knock-down studies pointed to the influence of integrin α5, CD44, and the Cyclin-CDK axis in regulating bladder cancer growth. Mistletoe extracts do block bladder cancer growth in vitro, with the molecular action differing according to the cell line and the host tree of the mistletoe. Integrating mistletoe into a guideline-based treatment regimen might optimize bladder cancer therapy.

In vitro analysis of quercetin-like compounds from mistletoe Dendrophthoe pentandra (L.) Miq as a potential antiviral agent for Newcastle disease.

Background: Recent evidence suggests that some flavonoid compounds obtained from crude methanol extract of mistletoe leaves ( Dendrophthoe pentandra L. Miq), also known as Benalu Duku (BD), have antimicrobial effects. Thus, the plant has the potential to eliminate viruses that may cause outbreaks in chicken farms. This study aimed to prove the in vitro ability of flavonoid compounds, namely quercetin-like compounds (QLCs), to eliminate field viruses, specifically the Newcastle disease virus (NDV). Methods: This research was performed in two stages. An in vitro test was used with a post-test of the control groups designed at a significance of 0.05. BD leaves (5 kg) were extracted using a maceration method with methanol and then separated into hexane, chloroform, ethyl acetate, and methanol fractions. The final extracted products were separated using semi-preparative high-performance liquid chromatography (HPLC) to obtain QLCs. The QLCs were identified and compared with quercetin using HPLC, proton and carbon nuclear magnetic resonance spectrometry, Fourier transform infrared spectrophotometry, and ultra-performance liquid chromatography-mass spectrometry. The activity of QLCs was tested in vitro against the NDV at a virulency titer of 10 -5 Tissue Culture Infectious Dose 50% (TCID50) and in chicken kidney cell culture. Results: Solutions of 0.05% (w/v) QLCs were discovered to have antiviral activity against NDVs, with an average cytopathogenic effect antigenicity at a 10 -5 dilution (p<0.05). Conclusions: QLCs from flavonoids from the leaves of BD have antiviral bioactivity against NDVs and may have the potential to be developed as medicinal compounds for the treatment of other human or animal viral infections.

In vitro analysis of quercetin-like compounds from mistletoe Dendrophthoe pentandra (L.) Miq as a potential antiviral agent for Newcastle disease

Background: Recent evidence suggests that some flavonoid compounds obtained from crude methanol extract of mistletoe leaves (Dendrophthoe pentandra L. Miq), also known as Benalu Duku (BD), have antimicrobial effects. Thus, the plant has the potential to eliminate viruses that may cause outbreaks in chicken farms. This study aimed to prove the in vitro ability of flavonoid compounds, namely quercetin-like compounds (QLCs), to eliminate field viruses, specifically the Newcastle disease virus (NDV). Methods: This research was performed in two stages. An in vitro test was used with a post-test of the control groups designed at a significance of 0.05. BD leaves (5 kg) were extracted using a maceration method with methanol and then separated into hexane, chloroform, ethyl acetate, and methanol fractions. The final extracted products were separated using semi-preparative high-performance liquid chromatography (HPLC) to obtain QLCs. The QLCs were identified and compared with quercetin using HPLC, proton and carbon nuclear magnetic resonance spectrometry, Fourier transform infrared spectrophotometry, and ultra-performance liquid chromatography–mass spectrometry. The activity of QLCs was tested in vitro against the NDV at a virulency titer of 10−5 Tissue Culture Infectious Dose 50% (TCID50) and in chicken kidney cell culture. Results: Solutions of 0.05% (w/v) QLCs were discovered to have antiviral activity against NDVs, with an average cytopathogenic effect antigenicity at a 10−5 dilution (p&lt;0.05). Conclusions: QLCs from flavonoids from the leaves of BD have antiviral bioactivity against NDVs and may have the potential to be developed as medicinal compounds for the treatment of other human or animal viral infections.

THE EFFECT OF DRY WHITE MISTLETOE EXTRACT ON THE CHANGE IN THE RATIO OF MITOCHONDRIAL SUBPOPULATIONS IN THE MYOCARDIUM IN ANIMALS WITH ALCOHOLIC CARDIOMYOPATHY

The aim of the research was to study the cardioprotective effect of dry white mistletoe extract in the context of assessing its effect on changes in the activity of interfibrillary and subsarcolemmal mitochondrial subpopulations of the myocardium in experimental alcoholic cardiomyopathy. Materials and methods. Alcoholic cardiomyopathy was modeled in female Wistar rats by course administration of ethanol at the rate of 3 g of absolute ethanol per 1 kg of animal body weight. The studied extract of white mistletoe leaves and the comparison drug – Trimetazidine – were administered orally at doses of 100 mg /kg and 35 mg/kg, respectively. Changes in troponin I concentration and serum creatine phosphokinase activity, citrate synthase activity in mitochondrial subpopulations, and the content of apoptosis markers – apoptosis-inducing factor and caspase 3 in myocardial tissue homogenate were determined during the work. Results and their discussion. The analysis of the results revealed that in rats with alcoholic cardiomyopathy, but without treatment, there is an increase in the concentration of troponin I and creatine phosphokinase activity, accompanied by an increase in the intensity of apoptosis reactions and citrate synthase activity of interfibrillary mitochondria. The use of Trimetazidine and the extract under analysis contributed to a decrease in troponin I content by 19.1% (p &lt; 0.05) and 24.4%, respectively, and creatine phosphokinase activity by 19.8% (p &lt; 0.05) and 28.4% (p &lt; 0.05). It was also established that the activity of subsarcolemmal mitochondria in animals treated with Trimetazidine and white mistletoe extract increased by 121.9% (p &lt; 0.05) and 306.3% (p &lt; 0.05) with a decrease in the activity of citrate synthase of interfibrillary mitochondria by 27.6% (p &lt; 0.05) and 41.4% (p &lt; 0.05). It should be noted that administration of the comparative drug and the studied extract to rats resulted in a decrease in cardiomyocytes' apoptosis, expressed in a decrease in the concentration of apoptosis-inducing factor and caspase 3. Conclusions. In conditions of alcoholic cardiomyopathy, the negative interfibrillary phenotype of mitochondria prevails, which can contribute to the development of energy deficiency in the heart muscle, increasing the degree of myocardial damage. Based on the data obtained, it can be assumed that the extract of white mistletoe contains an active substance of cardioprotective activity associated with restoring the energy metabolism and suppression of apoptosis in the myocardium.

The effect of dry extract of white mistletoe leaves on the change of vasodilation function of the cerebral vascular endothelium in rats with chronic alcohol intoxication

Aim to evaluate the effect of dry extract of mistletoe leafs on the change of vascular endothelium vasodilation function in rats under conditions of chronic alcohol intoxication.&#x0D; Material and methods. The chronic alcohol intoxication was modeled in female Wistar rats by course of oral administration of ethanol at the rate of 3g/kg/day. The tested extract and the reference drug ethylmethylhydroxypyridine succinate were administered per os at a dose of 100 mg/kg. The vasodilation function of the vascular endothelium was assessed by the change in the rate of cerebral blood flow during modification of the endogenous nitric oxide synthesis. The concentration of active forms of endothelial and inducible nitric oxide synthase isofrom was determined by enzyme immunoassay.&#x0D; Results. The course of the tested extract and the reference drug resulted in an increase in the rate of cerebral blood flow in relation to untreated animals by 48.1% (p0.05) and 40.2% (p0.05), respectively. The restoration of endothelium-dependent vasodilation of cerebral vessels was also noted with the administration of the studied extract of white mistletoe and the reference drug. The analysis of changes in the NO-synthase system showed that, when using the tested extract, the concentration of eNOS increased by 76.3% (p0.05), and iNOS, on the contrary, decreased by 22.1% (p0.05), which was comparable with the indicators of the group of animals receiving the reference drug.&#x0D; Conclusion. The use of mistletoe leaf dry extract leads to the restoration of endothelium-dependent vasodilation of cerebral vessels in rats with chronic alcohol intoxication, probably due to the improvement of eNOS-dependent mechanisms of nitric oxide synthesis.

Mistletoe Extracts during the Oncological Perioperative Period: A Systematic Review and Meta-Analysis of Human Randomized Controlled Trials.

We aim to evaluate the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period. Details registered a priori on PROSPERO (CRD42018086168). Seven RCTs (comprising 663 participants in nine reports) and three nonrandomized studies were included. In five RCTs, ME was evaluated as adjunctive care and the control group had no additional intervention, whereas in two RCTs, ME was compared head-to-head against common cancer treatments (i.e., etoposide or bacillus Calmette-Guérin) with the intervention groups not receiving standard care. Meta-analyses found no evidence for a difference between ME and no added therapy for mortality and recurrence (RR, 95% CI: 1.00, 0.79-1.27; and 1.03, 0.79-1.33, respectively). Two RCTs reported beneficial effects of ME on immune cells, specifically natural killer cells, in colorectal cancer, and one RCT reported quality of life improvement. Two RCTs reported ME discontinuations due to adverse events and grade 3/4 toxicities. Nevertheless, no safety signals were detected from these 10 studies. Quality appraisal revealed a substantial risk of bias. Preliminary data are encouraging for mistletoe extracts, particularly in the context of colorectal cancer. However, the evidence is limited by the number of studies, an evaluation of different outcomes, and methodological limitations. Further high-quality research is warranted.

Impact of aqueous extract of Viscum album on different organisms

The phytochemical and pharmacological potential of Viscum album extracts are widely used for the treatment of various diseases in many countries. The effect of aqueous extract from different mistletoe host trees (Abies alba, Acer saccharinum, Malus domestica, Pinus sylvestris) on model objects (Allium cepa and Drosophila milanogaster), bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus), and fungi (Aspergillus niger, Heterobasidion annosum, Inonotus obliquus) was evaluated. The influence of mistletoe extracts on A. cepa, D. melanogaster and basidiomycetes species H. annosum and I. obliquus was demonstrated for the first time. The study findings revealed that the impact of mistletoe aqueous extract exhibits considerable variation, influenced by multiple factors. These factors include the specific tree from which mistletoe is obtained, the concentration used, and the organism targeted. Mistletoe extracts caused the appearance of cells with pathologies in the meristematic tissues of A. cepa at different stages of the plant cell cycle. A clear cytostatic effect on A. cepa and D. melanogaster was shown, with the highest effect of mistletoe extract obtained from A. saccharinum. The main action of the solution on cells is probably manifested in the inhibition of cell division according to the results of the cytotoxicity assessment of aqueous extracts of mistletoe. Antibacterial activity of concentated mistletoe extract obtained from A. saccharinum was found only against S. aureus with zone of growth inhibition 11.0 ± 0.1 mm. In the assay on agar plates the tested extracts stimulated the mycelial growth of A. niger 1.85 times higher compared to the control, but inhibited the growth of H. annosum, I. obliquus at 65.5% and 62.2%, respectively. However, the biomass production of H. annosum was strongly dependent on the host mistletoe tree of the aqueous extract, and both the inhibition of mycelial synthesis of the wood-destroying fungus and its stimulating effect on mycelial accumulation were found. A negative effect (1.46 times decrease in biomass ) of H. annosum was found in the case of application of mistletoe extract obtained from A. saccharinum. The highest stimulation effect on fungus (1.53 times increase in biomass) was established by using mistletoe extract prepared from A. alba. In this study the main effects on living organisms used were indirectly caused by the host trees of mistletoe extracts. The overall negative impact was associated with the host tree Acer saccharinum.

Which is the More Effective Option for Pleurodesis to Prevent the Recurrence of Malignant Pleural Effusion? Large-Particle Talc or Mistletoe Extract (ABNOVA Viscum Injection).

Malignant pleural effusion affects many patients with advanced cancer. When chemotherapy or radiotherapy fails to relieve malignant pleural effusion and related symptoms, drainage and pleurodesis can help. Although surgical talc pleurodesis is the most widely used method, Viscum album, which has been recently used in surgical or bedside procedures, has demonstrated significant results and is as effective as talc. This study aimed to determine the most effective agent and procedure. Between January 2015 and July 2022, chemical pleurodesis was performed in 137 patients with malignant pleural effusion, using a V. album surgical procedure in 48, a V. album bedside procedure in 55, and a talc surgical procedure in 34 patients. We reviewed patients' clinical responses and disease progression after chemical pleurodesis. The success rate was not significantly different among the V. album surgical procedures (91.7%), V. album bedside procedures (83.6%), and talc surgical procedures (91.2%). However, the total drainage amount and tube insertion duration in both Viscum groups were more effective than those in the talc group. Furthermore, the bedside Viscum group showed significantly lower post-pleurodesis pain scores than the other 2 groups. According to our results, talc and V. album can be considered ideal agents for chemical pleurodesis. However, Viscum pleurodesis showed safer outcomes in terms of ensuring quality of life than talc. Additionally, the bedside Viscum group showed significantly lower pain scores than the other groups. Hence, patients for whom surgical procedures are inappropriate can undergo bedside Viscum pleurodesis without diminishing the therapeutic effect.

Component Composition and Some Features of the Biological Activity of &lt;i&gt;Viscum album&lt;/i&gt; (Viscaceae)

Abstract—The review summarizes data on the chemical composition and some features of biological activity of Viscum album L. (Viscaceae Batsch). Among the secondary metabolites, the dominant ones are: viscotoxins, lectins, carbohydrates, amino acids, flavonoids, triterpene acids, nitrogenous compounds. It has been shown that European mistletoe extracts, as well as individual components, exhibit various types of biological activity, including antitumor, immunomodulatory, antidiabetic, and improve cognitive functions. V. album is very promising for further comprehensive study as a local source of herbal preparations, as mistletoe preparations are prescribed as an adjunct treatment for cancer patients in many countries.

The impact of extract of mistletoe on tumour cells and hemostasis of human plasma

Background: The plant Viscum album (Mistletoe) is a known source of biologically active substances, used in traditional medicine in Europe and Asia.Aim: The goal was to study cytotoxic/cytostatic effect of mistletoe extract on tumour and normal cells and its influences on certain proteins of the blood coagulation system.Setting: Mistletoe was collected in Ukraine in November 2020.Methods: Water extract of V. album, both leaves and stems, was obtained and fractionated; it was characterised using high-performance liquid chromatography (HPLC) and mass spectrometry and tested on cancer cells and blood plasma.Results: Extract demonstrated the presence of viscotoxins and carbohydrates and thermolabile compounds that enhance the activity of thrombin and factor X in plasma in the presence of calcium ions and increased the activated partial thromboplastin time (APTT) by 2.7 times. The cytotoxic/cytostatic action of the mistletoe fractions, the total extract and the fraction 10 000 Da were higher in relation to Lewis lung carcinoma (LLC) cells than with Vero cells. The IC50 of total extract for LLC cells was 35% (p 0.05) lower than that for Vero cells (1.12 ± 0.2 and 1.71 ± 0.15 mg/ml). Thus, the IC50 of the fraction 10 000 Da for LLC cells was more than by 44% (p 0.05) lower than that for Vero cells (2.07 ± 0.26 and 3.67 ± 0.41 mg/ml).Conclusion: It was shown that both extracts exhibited a cytotoxic/cytostatic effect, more pronounced against tumour cells than normal cells and enhanced the clotting of blood plasma by thermolabile compounds by facilitating plasma coagulation.Contribution: This research makes it possible to study mistletoe as a light and cheap anticancer therapy plant and cure blood coagulopathy or construct antibleeding bandages.

Characterization of Mistletoe Leaves Growing on Fig Plant Found in NISLT, Samonda, Ibadan Premises

This study investigates the chemical composition of mistletoe leaves growing on fig tree. The mistletoe leaves and the fig leaves used for this research were harvested from Fig plant. Proximate analyses, phytochemical screening, Elemental and antioxidant analysis were done on both leaves. This study has provided a scientific justification that both the Fig leaves and Mistletoe leaves contained relevant phyto constituents such as alkaloids, saponins, flavonoid, and steroids; whereas antraquinones, tannins, phenols, resins and terpenoids were completely absent. Nutritionally relevant inorganic minerals like, Calcium, magnesium and potassium were the most abundant element in both plants. Proximate constituents like carbohydrates, lipids and proteins were present in varied amounts in both leaves. Result of inhibition of free radicals in fig leave extract increases with increase in concentration of the extract. The inhibition is closely comparable with that of the standard (Vitamin C) at the same concentration. The inhibition by the extracts of mistletoe grown on fig tree is low when compared with that of Fig and that of standard. This suggests that some of the chemical characteristics of mistletoe are conferred to them by their host trees.

Abstract 1600: Phase I trial of intravenous mistletoe extract in advanced cancer

Abstract Purpose: Mistletoe extract is widely used in cancer patients to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration. Patients and Methods: This phase I trial of intravenous Mistletoe (Helixor M) aimed to determine the recommended phase 2 dosing and to evaluate safety. Solid tumor patients progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL. Results: Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The maximum tolerated dose was 600mg. Treatment-related adverse events (AEs) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in three patients (14.8%). Stable disease was observed in five patients who had 1-6 prior therapies. Reductions in baseline target lesions were observed in three patients who had 2-6 prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by FACT-G increased from 79.7 at week 1 to 93 at week 4. Conclusions: Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted. Citation Format: Channing J. Paller, Lin Wang, Wei Fu, Rajedra Kumar, Jennifer Durham, Nilofer Azad, Daniel Laheru, Ilene Browner, Sushant Kachhap, Kavya Boyapati, Thomas Odeny, Deborah Armstrong, Christian Meyer, Stephanie Gaillard, Julie Brahmer, Ivelisse Page, Hao Wang, Luis A. Diaz. Phase I trial of intravenous mistletoe extract in advanced cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1600.

Effect of Extraction Solvent and Harvest Time on Recovery of Bioactive Com-pounds, Antioxidant and Cancer Cell Growth Inhibition Activities of Korean Ca-mellia mistletoe

This study aimed to determine the phytochemical profiles,in vitroantioxidant and antiproliferative properties of KoreanCamellia mistletoe(Korthalsella japon-ica(Thunb.) Engl.) depending on the harvest time (August and November) and sol-vent (100% methanol, 70% ethanol, and hot water). TheCamellia japonicaL. mistle-toe extracts were analyzed for total phenol, flavonoid, carotenoid, and L-ascorbic acid contents and antioxidant properties such as scavenging capacities (1,1-diphenyl-2-pic-rylhydrazyl (DPPH) and NO•),ferrous ion chelating and reducing power. Concur-rently, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as-say was used to assess the antiproliferative properties against human cancer cell lines; MCF (human breast cancer cells), HeLa (human cervical cancer cells), A375 (human malignant melanoma cells), HCT116 (human colon cancer cells), HepG2 (human liver cancer cells) and A549 (human non-small cell lung adenocarcinoma cells). The results showed that extraction solvent and harvest time had significant impacts on antioxidant and anticancer activities and selectivity for free phenolic compounds inCamellia ja-ponicaL. mistletoe. Among all the tested extracts, the highest amounts of total phe-nolic and total flavonoids content were found in ethanol extracts ofCamellia japon-icaL. mistletoe harvested in November, while the methanol extracts ofCamellia ja-ponicaL. mistletoe collected in August showed the highest contents of total carote-noids and L-ascorbic acidscompared to the other tested extracts. Additionally, the highest NO•radical scavenging activity was found in ethanol extracts, whereas the strongest DPPH radical scavenging activity was found in methanol extracts ofCamel-lia japonicaL. mistletoe harvested in November. Furthermore, methanol extracts showed much higher antiproliferative activity against all human cancer cells than eth-anol extracts ofCamellia japonicaL. mistletoe harvested in November. In conclusion, the antioxidant and anticancer properties ofCamellia japonicaL. mistletoe showed significant dependence on the extraction solvent type and harvest time. With optimum harvest time and extraction solvent, they boast a wide range of promising medical, pharmaceutical, and food applications

Quality of Life in Breast Cancer Patients Treated With Mistletoe Extracts: A Systematic Review and Meta-Analysis.

Breast cancer is the most common cancer type in women and quality of life an essential part of patients' well-being. Although the treatment with mistletoe extracts is covered by multiple cancer guidelines and reviews, it is uncertain whether mistletoe extracts can improve the quality of life in breast cancer patients. We therefore performed a systematic review and meta-analysis on this topic. This systematic review included randomized clinical trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the quality of life in breast cancer patients treated with mistletoe extracts as add-on therapy to control groups treated conventionally. We searched previous systematic reviews and multiple databases until January 2023. We conducted a meta-analysis and assessed the risk of bias according to the Cochrane Handbook via RoB 2 and ROBINS-I and the certainty of evidence via GRADE, respectively. Nine RCTs and 7 NRSIs with 833 and 2831 participants, respectively, were included. The pre-post changes for the quality of life resulted in a pooled standardized mean difference for RCTs of SMD = 0.61 (95% CI 0.47-0.75; P < .0001) and for retrospective NRSIs of SMD = 0.46 (95% CI 0.10-0.82; P = .01). The risk of bias was low to high for the RCTs and serious for all NRSIs. The certainty of evidence was moderate for RCTs and very low for NRSIs. Our results indicate a clinically relevant, medium-sized effect of mistletoe extracts on the quality of life in breast cancer patients which may be based on the immunomodulating effects of mistletoe extracts during chemotherapy. The limitations of evidence include the risk of bias which is mainly caused by the difficulty of blinding. Further RCTs and real-world evidence need to confirm this result, especially in the setting of neoadjuvant chemotherapy and in breast cancer survivors.

Preliminary studies of antioxidant and anti-inflammatory activities in methanol extracts of mistletoe (Dendrophthoe falcata) in guava (Psidium guajava)

Preliminary studies of antioxidant and anti-inflammatory activities in methanol extracts of mistletoe (Dendrophthoe falcata) in guava (Psidium guajava)

Systematic analysis of mistletoe prescriptions in clinical studies

PurposeMistletoe treatment is discussed controversial as a complementary treatment for cancer patients. Aim of this systematic analysis is to assess the concept of mistletoe treatment in the clinical studies with respect to indication, type of mistletoe preparation, treatment schedule, aim of treatment, and assessment of treatment results.MethodsIn the period from August to December 2020, the following databases were systematically searched: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL, and “Science Citation Index Expanded” (Web of Science). We assessed all studies for study types, methods, endpoints and mistletoe preparations including their ways of application, host trees and dosage schedules.ResultsThe search concerning mistletoe therapy revealed 3296 hits. Of these, 102 publications and at total of 19.441 patients were included. We included several study types investigating the application of mistletoe in different groups of participants (cancer patients of any type of cancer were included as well as studies conducted with healthy volunteers and pediatric patients). The most common types of cancer were breast cancer, pancreatic cancer, colorectal cancer and malignant melanoma. Randomized controlled studies, cohort studies and case reports make up most of the included studies. A huge variety was observed concerning type and composition of mistletoe extracts (differing pharmaceutical companies and host trees), ways of applications and dosage schedules. Administration varied e. g. between using mistletoe extract as sole treatment and as concomitant therapy to cancer treatment. As the analysis of all studies shows, there is no relationship between mistletoe preparation used, host tree and dosage, and cancer type.ConclusionsOur research was not able to deviate transparent rules or guidelines with respect to mistletoe treatment in cancer care.

Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish

Purpose The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. Methods Wild-type adult AB zebrafish were exposed to 45–50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. Results The median follow-up period was 10 d post-irradiation (range: 7–11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20–54.3) and 68.4% (95% CI:53.8–86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1β and IL-6) compared to the radiation alone group (p<.05). Conclusion The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

114 (PB-114) Poster - Exosomes from mistletoe treated tumor cells for the stimulation of immune cells

Background: Breast carcinoma is the most common and one of the most malignant tumors in women. Multimodal standard therapy currently increases the 5-year survival rate to over 80%. For some years now, complementary medicine has also been playing an increasingly role in the field of cancer therapy. In particular, mistletoe extract is used in breast cancer therapy to reduce the side effects of tumor therapy and to improve patients’ quality of life. Different approaches exist to stimulate the immune system.

Mistletoe extracts for cancer treatment

Mistletoe extracts for cancer treatment