Mistletoe Extract Research Articles

Complementary Treatment with Mistletoe Extracts During Chemotherapy: Safety, Neutropenia, Fever, and Quality of Life Assessed in a Randomized Study.

Objectives: Evaluate the safety and clinical response of complementary treatment with European mistletoe extracts during chemotherapy.Design: Monocentric controlled trial with 95 patients randomized into three groups.Settings/Location: National Cancer Research Center of Serbia.Subjects: Breast cancer patients (stage T1–3N0–2M0) undergoing surgery and adjuvant chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluorouracil.Interventions: Two different European mistletoe extracts (Helixor A, Iscador M Spez) were injected three times per week during 18 weeks of chemotherapy in the mistletoe group. Five-year follow-up of routine visits was documented in case report forms.Outcome measures: Safety was assessed by measuring adverse events, body temperature during chemotherapy, and probability of relapse or metastasis in a 5-year follow-up. During chemotherapy, the neutrophil count and quality of life according to EORTC QLQ-C30 were assessed.Results: The two patient groups receiving different complementary mistletoe treatments were integrated into one mistletoe group for this safety analysis. Patients in the mistletoe group did not develop more fever symptoms than patients in the control group (two short-term events in each group). No significant differences in probability of relapse or metastasis were measured between the groups (p = 0.7637). The mistletoe group showed a trend toward less neutropenia (p = 0.178) and improved pain and appetite loss scores (p < 0.0001 and p = 0.047, respectively) while having positive, but not significant, impact on other EORTC QLQ-C30 scores.Conclusions: Mistletoe extracts were safe in this clinical study. Neither did subcutaneous injections induce fever, nor did they influence the frequency of relapse and metastasis within 5 years. This result suggests that mistletoe extracts had no adverse interactions with the anticancer agents used in this study. Furthermore, certain side effects of chemotherapy decreased under this complementary treatment in breast cancer patients.

Immunological and Quality-of-Life Profiles in Women with Breast Cancer: Complementary versus Conventional Care

Background: Previous studies showed that women with breast cancer treated in anthroposophic clinic versus conventional care had increased quality of life (QoL) parameters, fighting spirit, and anxiety coping. We have now analyzed immune and QoL factors in these 2 groups for possible differences during the first 6 months after admission, prompted by anthroposophic studies, including mistletoe extracts, showing beneficial immune system effects. Patients and Methods: Fourteen immunological variables, including leukocyte count, lymphocyte count, activated T cells (CD4⁺ and CD8⁺), NK cells, B cells, IL1β, IL6, IL10, and oxytocin, were longitudinally analyzed in both groups (n = 2 × 26). A panel of QoL parameters were analyzed using 3 different instruments. Statistical evaluation included that each patient was its own control. Results: Cytotoxic CD8⁺ T cell frequency (percent of lymphocytes analyzed by flow-cytometry) significantly decreased over time in the anthroposophic group versus the conventional group (repeated measures ANOVA, p = 0.05). No major differences were observed in other immunological parameters, whereas QoL variables, anxiety decreased and physical symptoms increased/improved significantly in the anthroposophic group (p = 0.04 and p = 0.05, respectively). Conclusion: Overall, women with breast cancer in anthroposophic or conventional therapy did not differ in their immune profiles over time, with exception of decreased cytotoxic T cells in the anthroposophic group. Improvement in physical symptoms along with less anxiety in this group may have influenced the brain-immune axis resulting in lower frequency of CD8⁺ T cells, a feature associated with less aggressive cancer stages. To evaluate whether this observation is associated with good or bad prognosis, further detailed analyses of memory and naïve CD8⁺ T cells at tumor site and in blood circulation are essential.

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.

Taraxacum officinale extract shows antitumor effects on pediatric cancer cells and enhance mistletoe therapy

ObjectivesWhile Taraxacum officinale (dandelion) extracts showed antitumor effects on adult cancer cells, effects on pediatric tumor cells as a single agent or in combination with mistletoe extracts are hitherto unknown. Material and methodsThe anti-proliferative effects of an aqueous fermented Taraxacum officinale extract (Taraxacum) on a pediatric cancer cell line panel were assessed by cell viability assays (MTT). In two neuroblastoma cell lines, SH-SY5Y and Kelly, the effects on cell cycle distribution (PI staining), mitochondrial integrity (MitoTracker staining), invasion (Boyden chamber assay) and migration (Scratch-assay) as well as the synergistic effects of the co-treatment of Taraxacum and mistletoe preparations (Iscucin® Tiliae or Iscucin® Pini) were investigated. ResultsAll tested cancer cell lines were more susceptible to Taraxacum than the normal human fibroblast cell line, NHDF-C. In neuroblastoma cell lines Taraxacum caused apoptosis and loss of mitochondrial integrity as well as an inhibition of invasion and migration. The simultaneous therapy of Taraxacum and the mistletoe extracts revealed synergistic effects. ConclusionThis preclinical data support the use of Taraxacum as a potential adjuvant application in pediatric oncology.

In vitro inhibitory effects of mistletoes (Loranthus begwensis L.) phenolic-rich extracts on α-amylase, α-glucosidase, and angiotensin converting enzyme activities

This study focused on the effect of phenolic-rich extracts of mistletoe from different host plants on key enzymes (α-amylase, α-glucosidase) linked to type-2 diabetes (T2D) and hypertension (angiotensin-I converting enzyme [ACE]), as well as Fe2+ and sodium nitroprusside (SNP)-induced thiobarbituric acid reactive species (TBARS) production in rat pancreas in vitro. The phenolic-rich extract was prepared using ethyl acetate and the effects on α-amylase, α-glucosidase, and ACE activities, and TBARS production was determined. The phenolic constituent of the extract was also determined. The results revealed that the extracts (CCT, KNT, AMT, BFT) inhibited α-amylase (EC50 = 2.24, 2.59, 2.36, and 1.80 µg/mL, respectively), α-glucosidase (EC50 = 1.94, 1.92, 1.96, and 8.59 µg/mL), and ACE (EC50 = 0.87, 0.67, 0.75, and 1.06 µg/mL) activities, and Fe2+ and SNP-induced TBARS production. Therefore, inhibition of α-amylase, α-glucosidase, ACE, and oxidative stress by the phenolic-rich extracts could be among the mode of actions of mistletoe toward the management of T2D and hypertension. Practical applications Dried mistletoe leaves are usually consumed as tea or decoction, and are often prescribed for hypertensive or diabetic patients while the wet leaves are used to cook soup. This study revealed the possible antidiabetic, antihypertensive, and antioxidant properties of mistletoe leaves from different host plants.

Korean mistletoe lectin enhances natural killer cell cytotoxicity via upregulation of perforin expression.

Natural killer (NK) cells are crucial components of the innate immune system, providing the first line of defense against pathogens. In a previous study, we demonstrated prophylactic activity of water extract of Korean mistletoe (Viscum album coloratum) on tumor metastasis. However, the leading compound from water extract of Korean mistletoe was not clearly addressed. The purpose of this research was mainly focused on addressing the effect of Korean mistletoe lectin (KMLC) on NK cell cytotoxicity, and the ability of cytokine secretion as well as its signal transduction, mitogen-activated protein kinase (MAPK) pathway. KMLC was used to test NK cell-mediated cytotoxicity in vitro and in vivo. Non-isotope cytotoxicity assay (bis-N,N,N',N'-tetraacetic acid (BATDA) release assay) was performed to test the cytotoxicity of NK cells against target tumor cells. Receptor expression was checked by flow cytometry analysis and MAPK signal molecules were analyzed by immunoblotting. KMLC at 200 ng/mL increased the cytotoxicity of NK92 cells by 35% compared with untreated cells. KMLC-treated (at 100 ng/mL) mice splenocytes showed a 20% increase in cytotoxic activity. Also, the B chain, one of the subchains of KMLC, increases perforin expression. We demonstrated that the signal transduction controlling NK cell cytotoxicity was mediated by upregulation of the NKG2D receptor and expression of a cytotoxic effector molecule. These results suggested that KMLC possessed immunological activity, mediated by NK cell activation.

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

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. The aim of this study was the obtaining and the characterization of polymer structures containing mistletoe or garlic extract. 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. 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. 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.

Pleurodesis Using Mistletoe Extract Delivered via a Spray Catheter during Semirigid Pleuroscopy for Managing Symptomatic Malignant Pleural Effusion

Background: Talc poudrage during thoracoscopy is considered the standard procedure for patients with symptomatic malignant pleural effusion (MPE). Until now, no alternative technique other than talc poudrage for pleurodesis during medical thoracoscopy has been proposed. Liquid sclerosants, such as mistletoe extract, have been sprayed evenly into the pleural cavity during semirigid pleuroscopy for chemical pleurodesis. Objective: We conducted a retrospective study using the database of semirigid pleuroscopy to identify the usefulness of pleurodesis using a mistletoe extract delivered via a spray catheter during semirigid pleuroscopy for symptomatic MPE. Methods: All consecutive patients with symptomatic MPE who underwent semirigid pleuroscopy from October 2015 to September 2016 were registered. The responses were evaluated using chest X- ray or computed tomography 4 weeks after pleurodesis. Results: The study included 43 patients who underwent pleurodesis with mistletoe extract via a spray catheter during semirigid pleuroscopy. Complete and partial responses were seen in 21 (49%) and 19 (44%) patients, respectively. The median duration of chest tube placement after pleurod­esis was 7 days (range 6–8 days) in the 40 patients with complete or partial responses. No cases of severe hemorrhage, empyema formation, respiratory failure, or procedure-related mortality were observed in the subjects at 4 weeks after semirigid pleuroscopy. Conclusion: Pleurodesis with mistletoe extract delivered via a spray catheter during semirigid pleuroscopy is a safe and effective procedure for managing symptomatic MPE.

Mistletoe Extract in the Palliation of End Stage Cancer

Mistletoe Extract in the Palliation of End Stage Cancer

INHIBITORY ACTIVITIES OF CAMELLIA MISTLETOE (K. JAPONICA) EXTRACTS ON PANCREATIC LIPASE, TYROSINASE AND CANCER CELL PROLIFERATION

Objective: The objective of this study was undertaken to examine pancreatic lipase and tyrosinase inhibitory activities of Camellia mistletoe (Korthalsella japonica) extracts and conduct their antiproliferative activity on several human cancer (Hela, A375, HCT 116, HepG2 and A549) and normal cells (TK6) lines.Methods: The lipase inhibitory activity of acts of Camellia mistletoe extracts were determined from the hydrolytic reaction of p-nitrophenyl butyrate with pancreatic lipase and cytotoxicity against human cancer and normal cell lines were also evaluated using the MTT assay. The in vitro tyrosinase inhibitor potency of Camellia mistletoe extracts was estimated using mushroom tyrosinase.Results: Both methanol and ethanol extracts of Camellia mistletoe exhibited an inhibitory effect on lipase inhibition activity with IC50 values of 0.39 and 0.49 mg/ml, respectively. Moreover, Camellia mistletoe extracts were judged to be strongly active against the cancer cell lines, while they had no antiproliferative activity against the normal human cell lines. However, they had little inhibitory effects on tyrosinase activity.Conclusion: Camellia mistletoe extracts could be the good sources of natural lipase inhibition and anticancer agents with a great potential to be used in food and therapeutic fields.

Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells

BackgroundMistletoe extract of Visucm album extract (VAE) contains many biologically active components and has been reported to be not only a complementary and alternative medicine, but also a potent therapeutic agent for many types of cancer. PurposeIn this study, we examined the effect of VAE on expression and activation of Axl and scrutinized the involvement of Axl in the anti-cancer activity of VAE in parental and chemo-resistant non-small cell lung cancer (NSCLC) cells. MethodsThe levels of Axl protein and mRNA were determined by Western blot analysis and RT-PCR, respectively. Phosphorylation of Axl upon Gas6 stimulation was observed by Western blot analysis. For ectopic expression or gene silencing of Axl, the recombinant plasmid, pcDNA3-Axl, or specific siRNA targeting Axl were transfected into A549 and H460 cells using Lipofectamine 2000, respectively. The anti-cancer activity of mistletoe extract was examined against the parental cells and each of their cisplatin- or erlotinib-resistant cells using trypan blue exclusion assays and colony formation assay. ResultsThe levels of Axl mRNA were also reduced by VAE treatment, implying the transcriptional downregulation of Axl expression by VAE. In addition, the phosphorylation of Axl protein upon its ligand, Gas6, stimulation was found to be abrogated by VAE. We next found cytotoxic effect of VAE on both the parental NSCLC cells and their variants which are resistant to cisplatin (A549/CisR and H460/CisR) or erlotinib (H460/ER and H1975/ER). Treatment of these cells with VAE caused a dose-dependent decrease of cell viability and clonogenicity. This anti-proliferative effect of VAE was attenuated in Axl-overexpressing cells, while it was augmented in cells transfected Axl specific siRNA. Next, we also found that in cisplatin-resistant cells and erlotinib-resistant cells, VAE treatment decreased Axl protein level, colonogenicity. The levels of several cell cycle regulator, p21 and apoptosis related protein, X-linked inhibitor of apoptosis, was found to be induced and reduced by VAE treatment, respectively. ConclusionTaken together, our data provide that VAE targets Axl to suppress cell proliferation and to circumvent cisplatin- and erlotinib-resistance in NSCLC cells.

Safety of intravenously applied mistletoe extract \u2013 results from a phase I dose escalation study in patients with advanced cancer

BackgroundMistletoe extracts have anti-tumor properties and are approved for subcutaneous use in cancer patients. Data on Intravenous application are limited.MethodsAn 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.ResultsTwenty-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.ConclusionWeekly 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).

Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model.

Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.

Proteomic fingerprinting of mistletoe (Viscum album L.) via combinatorial peptide ligand libraries and mass spectrometry analysis

Combinatorial peptide ligand libraries (CPLLs), coupled to mass spectrometry (MS) analysis, have been used to investigate in depth the proteome of Viscum album L. (VA), commonly named European mistletoe, in order to provide a first proteomic fingerprinting. For this purpose, the proteins were captured via CPLLs at two different pH values (acidic and neutral). A total of 648 non-redundant proteins were identified by using two different databases. The two pH values, chosen for bead incubations, have contributed to increment the capture ability: 56% and 31% of CPLLs species were respectively recognized at pH7.2 and at pH2.2. Finally the biological function of identified proteins was evaluated in order to understand their role on human health and the potential benefits of mistletoe extracts in medicine. SignificanceViscum album L. (VA) extracts are recently used as supporting medicine for cancer therapy, improving patients' survival and increasing their quality of life in medicine. These anticancer effects are investigated and they are probably due to mistletoe's capability to favor tumor cell's death and to modulate the immune system. Although the increasing interest in VA medical benefits, the role of its components in human health remains unclear. In order to exploit this aspect, it is important to comprehensively study proteins present in Viscum album L. (VA) extracts. Nevertheless, since plant proteomics analysis is in most cases handicapped by the presence of high-abundance proteins masking the detection of the low-abundance ones, it is important to overcome this challenge. In this sense, combinatorial peptide ligand libraries (CPLLs) have been used to reduce the dynamic protein concentration range to enable the identification of a higher amount of proteins than employing conventional methods. In this work, a total of 648 non-redundant proteins were identified: 56% and 31% of CPLLs species were respectively recognized at pH7.2 and at pH2.2. This deep proteome identification was useful to investigate the biological functions of proteins in order to evaluate their potential role in human health.

Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (Viscum album L.) Extract

Background: The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay. Material and Methods: 32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out. Results: MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly. Conclusion: This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.

근위축 마우스 모델에서 한국산 겨우살이 추출물에 의한 단백질 합성 신호전달 경로의 활성화

근위축 마우스 모델에서 한국산 겨우살이 추출물에 의한 단백질 합성 신호전달 경로의 활성화

Transcriptomic and proteomic insight into the effects of a defined European mistletoe extract in Ewing sarcoma cells reveals cellular stress responses

BackgroundThe hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo.MethodsWe recreated a total mistletoe effect (viscumTT) by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of viscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling.ResultsTreatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of viscum, TT and viscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While viscum and viscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy.ConclusionsSince the combinatory extract viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.

Polymeric sorbents modified with gold and silver nanoparticles for solid-phase extraction of proteins followed by MALDI-TOF analysis

The authors describe four different kinds of sorbents for solid-phase extraction (SPE) and preconcentration of proteins from complex samples. All are based on the use of a poly(glycidyl-co-ethylene dimethacrylate) host monolith that was chemically functionalized by using two different ligands (ammonia and cysteamine). Gold nanoparticles (AuNPs) or silver NPs were then assembled to the amino or thiol groups. The resulting materials are shown to be viable stationary phases for use in SPE cartridges. The sorbents can selectively retain bovine serum albumin, and the thiol-modified sorbents containing AuNPs and AgNPs provide the highest recoveries (>90%) and satisfactory loading capacities (29.3 and 17.6 μg⋅mg−1 of sorbent, respectively). The applicability of these nanosorbents was demonstrated by preconcentrating viscotoxins from mistletoe extracts. The enriched fractions were subjected to MALDI-TOF analysis to underpin their selectivity.

Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy

BackgroundKorean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle.MethodsWe examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model.ResultsInterestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice.ConclusionsOur results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs

BackgroundOsteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids. However, both hydrophilic and hydrophobic triterpenic acids possess anti-cancer properties. In this study, a whole mistletoe extract viscumTT re-created by combining an aqueous extract (viscum) and a triterpene extract (TT) was tested for its anti-cancer potential in osteosarcoma.MethodsTwo osteosarcoma cell lines were treated with three different mistletoe extracts viscum, TT and viscumTT to compare their apoptotic potential. For this purpose, annexin/PI staining and caspase-3, −8 and −9 activity were investigated by flow cytometry. To determine the mechanism of action, alterations in expression of inhibitors of apoptosis (IAPs) were detected by western blot. Apoptosis induction by co-treatment of viscum, TT and viscumTT with doxorubicin, etoposide and ifosfamide was examined by flow cytometry.ResultsIn vitro as well as ex vivo, the whole mistletoe extract viscumTT led to strong inhibition of proliferation and synergistic apoptosis induction in osteosarcoma cells. In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down-regulation after viscumTT treatment. In addition, co-treatment with doxorubicin, etoposide and ifosfamide further enhanced apoptosis induction, also synergistically.ConclusionViscumTT treatment results in synergistic apoptosis induction in osteosarcoma cells in vitro and ex vivo. Additionally, conventional standard chemotherapeutic drugs such as doxorubicin, etoposide and ifosfamide were able to dramatically enhance apoptosis induction. These results promise a high potential of viscumTT as an additional adjuvant therapy approach for osteosarcoma.