Viscum Album Coloratum Research Articles

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.

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

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

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.

A Fomitopsis pinicola Jeseng Formulation Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity.

This study investigated the antiobesity effect of an extract of the Fomitopsis pinicola Jeseng-containing formulation (FAVA), which is a combination of four natural components: Fomitopsis pinicola Jeseng; Acanthopanax senticosus; Viscum album coloratum; and Allium tuberosum. High-fat diet- (HFD-) fed male C57BL/6J mice were treated with FAVA (200 mg/kg/day) for 12 weeks to monitor the antiobesity effect and amelioration of nonalcoholic fatty liver diseases (NAFLD). Body and white adipose tissue (WAT) weights were reduced in FAVA-treated mice, and a histological examination showed an amelioration of fatty liver in FAVA-treated mice without decreasing food consumption. Additionally, FAVA reduced serum lipid profiles, leptin, and insulin levels compared with the HFD control group. The FAVA extract suppressed lipogenic mRNA expression levels from WAT concomitantly with the cholesterol biosynthesis level in the liver. These results demonstrate the inhibitory effects of FAVA on obesity and NAFLD in the diet-induced obese (DIO) mouse model. Therefore, FAVA may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet.

Expression of recombinant viscum album coloratum lectin B-chain in the silkworm expression system and evaluation of antioxidant activity

Korean mistletoe lectins (KMLs) possess many biological activities, including anti-tumor, apoptosis-inducing, anti-metastatic, and anti-angiogenic activities. Recombinant KML-1A (rKML-1A) has been previously expressed in soluble form in Escherichia coli cells. However, the expression of rKML-1B in soluble form remains to be accomplished. In this study, we describe the production, purification, and characterization of recombinant KML-1B by using a baculovirus expression system, which employs silkworm larvae and pupae as hosts. Approximately 495 and 702 µg/mL of a 36-kDa rKML-1B protein were produced without a signal peptide by silkworm larvae and pupae, respectively. Treatment of the recombinant protein with N- or O-deglycosylase led to a decrease in its molecular mass, indicating the N-and/or O-glycosylation of rKML-1B. Purified rKML-1B displayed radical scavenging activities toward 1,1-diphenyl-2-picrylhydrazyl and 2,2′-amino-di-[3-ethylbenzthiazoline sulfonate], with a half maximal inhibitory concentration (IC50) of approximately 95 µg/mL. This activity was discovered to be stable at 65°C. To our knowledge, this is the first report detailing the biological activity of plant-derived, pure rKML-1B.

Complementary and alternative medicine for diabetes 2014.

Complementary and alternative medicine for diabetes 2014.

Viscothionin isolated from Korean mistletoe improves nonalcoholic fatty liver disease via the activation of adenosine monophosphate-activated protein kinase.

The present study investigated the effects of viscothionin, a compound isolated from Korean mistletoe (Viscum album coloratum), on nonalcoholic fatty liver disease (NAFLD) in both in vitro and in vivo models. A connection was discovered between viscothionin and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is involved in lipid metabolism. Viscothionin was shown to significantly attenuate lipid accumulation in HepG2 cells treated with oleic acid, which induces lipid accumulation. Moreover, the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HepG2 cells was increased by viscothionin treatment. Viscothionin was orally administered to high fat diet-induced obese mice and subsequently histopathological analysis associated with AMPK signaling pathways was evaluated. A significant reduction in the extent of hepatic steatosis was revealed in viscothionin-treated obese mice. Thus, viscothionin mediates its beneficial effects on NAFLD via AMPK signaling pathways, suggesting that it may be a potential target for novel NAFLD treatments.

Protein Fractions from Korean Mistletoe (Viscum Album coloratum) Extract Induce Insulin Secretion from Pancreatic Beta Cells

Mistletoe (Viscum Album coloratum) has been known as a medicinal plant in European and Asian countries. Recent data show that biological activity of mistletoe alleviates hypertension, heart disease, renal failure, and cancer development. In this study, we report the antidiabetic effect of Korean mistletoe extract (KME). KME treatments enhanced the insulin secretion from the pancreatic β-cell without any effects of cytotoxicity. PDX-1 and beta2/neuroD known as transcription factors that regulate the expression of insulin gene were upregulated by treatment of the KME protein fractions isolated by ion-exchange chromatography after ammonium sulfate precipitation. Furthermore, these KME protein fractions significantly lowered the blood glucose level and the volume of drinking water in alloxan induced hyperglycemic mice. Taken together with the findings, it provides new insight that KME might be served as a useful source for the development of medicinal reagent to reduce blood glucose level of type I diabetic patients.

Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies

Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50μg/ml extended the mean survival time by 9.61 and 19.86% in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.

Isolation and partial characterization of heparin-binding protein from Korean mistletoe (Viscum album coloratum)

Korean mistletoe (Viscum album coloratum), a different subspecies of Viscum album from European mistletoe has shown that it has various biological activities including anti-cancer and immune modulating activities. The main leading compounds were known to be lectins. Additionally, we isolated heparin-binding protein (HBP) fractions from Korean mistletoe extract (KM) and characterized them. Heparin is a highly sulfated polysaccharide that is used clinically as anticoagulant. More than 100 HBPs with various biological activities are identified. These proteins fall into diverse groups, including circulatory system, several growth factors, extracellular matrix and lipid metabolism. HBP fractions of Korean mistletoe were isolated by heparin-conjugated sepharose affinity chromatography and were characterized in terms of molecular weight, partial sequencing, and biological activities. The isolated HBP fractions showed strong cytotoxicity against human and murine tumor cell lines. Furthermore, the inhibitory effectors on tumor angiogenesis and tumor growth were observed. In immunomodulating activity, HBP fractions induced the production of several cytokines such as TNF-α, IL-1β and IL-6 in mouse peritoneal cells and NO production in RAW 264.7 cells. Results demonstrated that the isolated HBP fractions may have the potential to be used as anti-tumor and immunomodulating agents. Key words: Heparin binding protein, mistletoe.

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes

Globally, the incidence of obesity, metabolic syndrome, and diabetes (OMD) are continuously on the rise because of rapid changes in human life-style and dietary habits. Herbal extracts are of special interest in treating combination of these diseases because of their multipronged mode of action. The list of potential herbals to control metabolic diseases is ever-expanding. However, because of poor characterization and safety issues, these herbs face limitations for their clinical usage. This special issue is a collection of research and review articles on preclinical and clinical benefits of herbals in controlling OMD. This special issue contains 24 articles accepted from a total of 37 submissions consisting of 20 research articles, 3 review articles, and 1 clinical study. The research articles in this issue can be broadly divided into three disease categories—nonalcoholic steatohepatitis (NASH), obesity, and diabetic complications. Four articles of this special issue focus on evaluating the protective role of herbal extracts on NASH. The studies by X. R. Yang et al. “Effect of dietary cocoa tea (Camellia ptilophylla) supplementation on high-fat diet-induced obesity, hepatic Steatosis, and hyperlipidemia in mice” and H.-Y. Jung et al. “The Korean mistletoe (Viscum album coloratum) extract has an antiobesity effect and protects against hepatic steatosis in mice with high-fat diet-induced obesity” report the potential benefits of Camellia ptilophylla and Viscum album coloratum extracts against HFD-induced NASH. Another two articles evaluated protective effects of biherbal combination (S. miltiorrhiza, G. jasminoides and Grape Pomace, Omija Fruit) in ameliorating experimental NASH. This special issue also contains five articles that focus on antiobesity potential of herbal extracts. These detailed studies evaluated the benefits of 10 herbs and their potential mechanisms responsible in controlling obesity using experimental HFD-fed mice/rat in vivo and 3T3L1 preadipocyte in vitro models. Modulation of PPARγ was a key antiobesity mechanism of Artemisia iwayomogi, Codonopsis lanceolata, Populus balsamifera and its active component (salicortin), and beta-glucan-rich extract from Pleurotus sajor-caju (Fr.) Singer. H.-Y. Shin et al. reported an activation of AMP-activated protein kinase by extract of six herbal medicines (OB-1). In this special issue, 11 articles focus on the potential benefits of various herbal extracts/phytocompounds on diabetes-induced insulin resistance, nephropathy, retinopathy, cardiomyopathy, and inflammation. A. l. Al-Malki showed oat extract to be beneficial for diabetic nephropathy and retinopathy by modulating nuclear factor kappa B (NF-kB). Inhibition of aldose reductase activity by scopoletin ameliorated cataractogenesis in galactose-fed rats (J. Kim et al.). Boehmeria nivea extract (S. H. Kim et al.) and swertiamarin (T. P. Patel et al.) regulated experimental insulin resistance by modulating PPARγ. In another report, S. Kadan et al. evaluated effect of eight antidiabetic medicinal plants extracts on GLUT 4 translocation. The benefits of fisetin and an ayurvedic herbal formulation (Kal-1) on diabetes-induced inflammation was also reported. Further, quercetin was shown to preserve β-cell mass and function in fructose-fed hyperinsulinemic rats via modulating pancreatic akt/foxo1 activation. Berberine ameliorated glucose- and insulin-induced cardiomyocyte hypertrophy by modulating PPARα/NO. In an interesting article by S. E. Martinez et al. pharmacometrics of an antidiabetic compound, 3-methoxypterostilbene was reported. 3-Methoxypterostilbene inhibited α-glucosidase and α-amylase activity and exhibited approximately 50% bioavailability. Three review articles were also incorporated in this special issue. A review by Y. Liu et al. (recent updates on beneficial role of berberine in controlling NASH) provides detailed account on molecular regulation of lipid metabolism and NASH by berberine. In another review by C. D. Lorenzo et al. the use of in vitro and clinical approaches to assess the benefits of plant food supplements is critically discussed. The potential benefits of Kampo, a Japanese traditional medicine, in treating obesity was reviewed by J.-i Yamakawa et al. based on basic and clinical evidence. The only clinical study as a part of this special issue focuses on evaluating body weight lowering effects of herbal extract-THI (target herbal ingredient) on exercising healthy overweight humans following a two-month randomized double-blind, placebo-controlled trial. The study reports a significant reduction in body weight indicating its potential antiobesity effect. We envisage that this special issue will attract broad interest in the fields of obesity, metabolic syndrome, and type 2 diabetes and encourage the perusal of in-depth molecular and cellular mechanistic investigations into the use of natural products, in particular the herbal therapies for metabolic disorders and their complications.

The Korean Mistletoe (Viscum album coloratum) Extract Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity

This study investigates the inhibitory effects of Korean mistletoe extract (KME) on adipogenic factors in 3T3-L1 cells and obesity and nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet. Male C57Bl/6 mice fed a high-fat diet were treated with KME (3 g/kg/day) for 15 weeks for the antiobesity and NAFLD experiments. Body weight and daily food intake were measured regularly during the experimental period. The epididymal pad was measured and liver histology was observed. The effects of KME on thermogenesis and endurance capacity were measured. The effects of KME on adipogenic factors were examined in 3T3-L1 cells. Body and epididymal fat pad weights were reduced in KME-treated mice, and histological examination showed an amelioration of fatty liver in KME-treated mice, without an effect on food consumption. KME potently induces mitochondrial activity by activating thermogenesis and improving endurance capacity. KME also inhibited adipogenic factors in vitro. These results demonstrate the inhibitory effects of KME on obesity and NAFLD in mice fed a high-fat diet. The effects appear to be mediated through an enhanced mitochondrial activity. Therefore, KME may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet.

Complementary and Alternative Medicine for Diabetes

Complementary and Alternative Medicine for Diabetes

Korean Mistletoe (Viscum album coloratum) Extract Improves Endurance Capacity in Mice by Stimulating Mitochondrial Activity

The beneficial effects of exercise on overall health make it desirable to identify the orally active agents that enhance the effects of exercise in an effort to cure metabolic diseases. Natural compounds such as resveratrol (RSV) are known to increase endurance by potentiating mitochondrial function. Korean mistletoe (Viscum album coloratum) extract (KME) has characteristics similar to those of RSV. In the present study, we determined whether KME could increase mitochondrial activity and exert an anti-fatigue effect. We found that KME treatment significantly increased the mitochondrial oxygen consumption rate (OCR) in L6 cells and increased the expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and silent mating type information regulation 2 homolog 1 (SIRT1), two major regulators of mitochondria function, in C2C12 cells. In the treadmill test, KME-treated mice could run 2.5-times longer than chow-fed control mice. Additionally, plasma lactate levels of exhausted mice were significantly lower in the KME-treated group. In addition, the swimming time to exhaustion of mice treated with KME was prolonged by as much as 212% in the forced-swim test. Liver and kidney histology was similar between the KME-treated and phosphate-buffered saline-treated animals, indicating that KME was nontoxic. Taken together, our data show that KME induces mitochondrial activity, possibly by activating PGC-1α and SIRT1, and improves the endurance of mice, strongly suggesting that KME has great potential as a novel mitochondria-activating agent.

The effect of mistletoe, Viscum album coloratum, extract on innate immune response of Nile tilapia (Oreochromis niloticus)

The purpose of the present study was to evaluate the effect of dietary mistletoe extracts on non-specific immune response and disease resistance of Nile tilapia (Oreochromis niloticus) against Aeromonas hydrophila infection. Tilapia fingerlings were fed with a diet containing 0 mg as a control, 10 mg, 50 mg, and 200 mg mistletoe powder kg−1 dry diet for 80 days. The immunological parameters, respiratory burst activity, lysozyme activity, alternative complement haemolysis activity (ACH50), and phagocytic activity of fish were investigated following 20, 40 and 80 days of feeding. Fish were challenged with A. hydrophila on 80 days after feeding and mortalities were checked over 10 days post-infection. The results show that fish fed with mistletoe extract exhibited an increase in activity in all immunological parameters (P < 0.05) compared to the control group depending on feeding periods and doses of mistletoe. Following challenge with A. hydrophila, 42% less survivability was observed in the control group than in other experimental diet groups. The highest survival rate (83%) was shown in the group fed with a 50 mg mistletoe kg−1 diet. The results suggest that mistletoe enables tilapia to promote immunity and be more resistant to A. hydrophila infection.

A latex lectin from Euphorbia trigona is a potent inhibitor of fungal growth

In this study we identified and characterized a major latex lectin - designated as EtLLH - with antimicrobial activity from the succulent African milk tree Euphorbia trigona. The lectin is highly concentrated in the latex of E. trigona and appears to be composed of at least two subunits with a molecular mass of 32 kDa. EtLLH shares significant similarities to known plant lectins - ricin from Ricinus communis and agglutinin from Viscum album coloratum - which specifically bind D-galactose and N-acetyl-D-glucosamine, the major building blocks of many fungal cell walls. Antimicrobial activity assays revealed an impact of EtLLH on three phytopathogenic filamentous ascomycetes. The germination of the conidiospores and the hyphal growth of Aspergillus niger and Fusarium graminearum were severely inhibited by EtLLH already at concentrations below 0.1 mg cm-3, while the effect on germination of the melanized conidiospores of Botrytis cinerea was less significant.

Protective Effects of Korean Mistletoe Lectin on Radical-Induced Oxidative Stress

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.

Biomarkers Identified by Proteomic Study of Spleen Lymphocyte from Broilers Infected with Salmonella gallinarum after Feeding Korean Mistletoe (Viscum album coloratum)

Biomarkers Identified by Proteomic Study of Spleen Lymphocyte from Broilers Infected with Salmonella gallinarum after Feeding Korean Mistletoe (Viscum album coloratum)

Antimutagenicity and anticancer effect of Korean mistletoe (viscum album coloratum) in HT‐29 human colon carcinoma cells

The antimutagenic and anticancer effects of Korean mistletoe (Viscum album coloratum) were investigated under in vitro and cellular system using HT‐29 human colon carcinoma cells. The water extract from the mistletoe showed antimutagenity against mutagenicities induced by aflatoxin B1 and N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in Salmonella typhimurium TA100 as concentration dependent‐manner. Moreover, under HT‐29 cellular model, the mistletoe extract led significant decreases in cell viability in MTT assay and growth inhibition test. The results of DAPI staining showed that mistletoe extract induced apoptosis in HT‐29 cells and the ratio of apoptotic body increased as dose dependent. Mistletoe‐induced apoptosis in HT‐29 cells was associated with the decreased expression of the anti‐apoptotic Bcl‐2 and a concomitant increase of the pro‐apoptotic Bax protein and mRNA. In addition, mistletoe treatment induced marked accumulation of tumor suppressor p53 and an induction of cyclin‐dependent kinase inhibitor p21. The present study suggests that Korean mistletoe extract would have the chemopreventive effects.

Korean Mistletoe (Viscum albumColoratum) Extract Induces Eel (Anguilla japonica) Non-specific Immunity

The immunomodulatory effects of Korean mistletoe (Viscum album Coloratum) on the innate immune responses of eel (Anguilla japonica) were studied. Methods: Mistletoe, Freund’s complete adjuvant (FCA), or phosphate-buffered saline (PBS) as a control was injected into eel peritoneal cavities. Results: Nitroblue tetrazolium (NBT)-positive cells in the head kidney of eel were significantly augmented by the second day post-injection of mistletoe. Reactive oxygen intermediates (ROI) were more produced in mistletoe-injected fish kidney leucocytes than in FCA-injected ones. The level of lysozyme activity in the serum of fish 2 days after injection with mistletoe was also significantly higher than that in the serum of the control fish. The optimal concentration of mistletoe in inducing the highest serum lysozyme activity was revealed to 500μg/200 g of fish. In phagocytic activity assay, mistletoe-sensitized eel kidney phagocytes captured more zymosan than did the control fish. Conclusion: Korean mistletoe appeared to be a good activator of the non-specific immune responses of eel.