• Archives of Pharmacal Research
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• v.27 no.8
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• pp.840-844
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• 2004

A triterpene was isolated as a cytotoxic principle from the dichloromethane extract of Korean mistletoe (KM； Viscum album colora turn) by repeated silica gel chromatography and recrystalli-zation. In in vitro analysis of cytotoxic activity using various human and murine tumor cell lines, the dichloromethane extract of KM was highly cytotoxic against these cells. We isolated the most active compound, referred to VD-3, from the dichloromethane extract of KM. The VD-3 was shown to be less cytotoxic to normal cells (murine splenocytes). From the identification of the chemical structure of VD-3 by spectral data and chemical synthesis, the compound was proven to be epi-oleanolic acid. Tumor cells treated with VD-3 showed a typical pattern of apo-ptotic cell death, such as apparent morphological changes and DNA fragmentation. These results indicate that epi-oleanolic acid is an important compound responsible for antitumor activity of KM.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.429-435
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• 1998

Lectins and its A- and B-chains from Korean mistletoe (Viscum album var. coloratum) were isolated by affinity chromatography on the Sepharose 4B modified by lactose-BSA conjugate synthesized by reductive amination of ligand (lactose) to .epsilon.-amino groups of lysine residues of spacer (BSA) after reduction by $NaCNBH_3$. The lactose-BSA conjugate was coupled to Sepharose 4B activated by cyanogen bromide. The molecular weight determined by SDS-PAGE were a 31 kD of A-chain and a 35kD of B-chain. Amino acid analysis and N-terminal sequencing were performed. The effects of pH, temperature and guanidine chloride on the conformation of the lectin were investigated by measuring its intrinsic fluorescence and compared with its hemagglutinating activities. Blue shift was detected on the acidic pH and there was a close relationship between activities and conformation of the lectin. Under denaturing conditions, the tryptophan emission profile of lectin showed typical denaturaiional red shift which also correspond to the conformations and activity of lectin.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.630-637
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• 2016

The chemical components and biological activity of Camellia mistletoe, Korthalsella japonica (Loranthaceae) are relatively unknown compared to other mistletoe species. Therefore, we investigated the phytochemical properties and biological activity of this parasitic plant to provide essential preliminary scientific evidence to support and encourage its further pharmaceutical research and development. The major plant components were chromatographically isolated using high-performance liquid chromatography and their structures were elucidated using tandem mass spectrometry and nuclear magnetic resonance anlysis. Furthermore, the anti-inflammatory activity of the 70% ethanol extract of K. japonica (KJ) and its isolated components was evaluated using a nitric oxide (NO) assay and western blot analysis for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Three flavone di-C-glycosides, lucenin-2, vicenin-2, and stellarin-2 were identified as major components of KJ, for the first time. KJ significantly inhibited NO production and reduced iNOS and COX-2 expression in lipopolysaccharide-stimulated RAW 264.7 cells at $100{\mu}g/mL$ while similar activity were observed with isolated flavone C-glycosides. In conclusion, KJ has a simple secondary metabolite profiles including flavone di-C-glycosides as major components and has a strong potential for further research and development as a source of therapeutic anti-inflammatory agents.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.68-76
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• 2004

Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.

• Korean Journal of Pharmacognosy
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• v.34 no.3 s.134
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• pp.210-217
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• 2003

Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse splenic macrophages to produce tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}$) and might play a role in anticancer. To know the effect of M11C on the production of $TNF-{\alpha}$, the splenic macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated splenic macrophage-conditioned media; MSCM). MSCM was analyzed for the $TNF-{\alpha}$ secretion by means of ELISA and immunoblotting, and mRNA expression was analyzed by RT-PCR. The S-180 murine sarcoma model was established to know the effect of M11C on the inhibition of tumor growth. M11C had the effect of $TNF-{\alpha}$ production from splenic macrophages performed by ELISA technique. This ELISA data was reconfirmed by immunoblotting assay. The effects of M11C on the expression of $TNF-{\alpha}$ mRNA from the macrophages was also shown. M11C also had the inhibitory effect of S-180 tumor growth. These data suggest that Korean mistletoe extract M11C may be used for an immunomodulator.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.10
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• pp.1594-1600
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• 2004

Effects of mistletoe (Viscum album) extract and pueraria (Pueraria radix) extract on cellular NF-$textsc{k}$B activity were evaluated in human malignant keratinocytes (SCC-13) to elucidate the possible correlation of NF-$textsc{k}$B with antioxidant activity. The antioxidant activities of these natural extracts were examined in four different evaluation methods, i.e., lipid peroxidation value (POV) evaluation test, I,l-diphenyl-2-picrylhydrazyl radical (DPPH), nitric oxide (NO) scavenging test, and reducing power assay. Pueraria extract (0.5 mg) and mistletoe extract (5 mg) downregulated the cellular NF-$textsc{k}$B activation up to 35% and 10% compared to the control, respectively, although their effects were lower than the known NF-$textsc{k}$B downregulator, vitamin C (8.8 mg, 53%) in a cell-based NF-$textsc{k}$B activity assay system. In the POV test, relative antioxidant activities of mistletoe extract (86%) and pueraria extract (75%) were significantly higher than the known antioxidant, vitamin C (48%) at the same concentration (10 mg) and the degree of activity increased in a dose-dependent manner. Pueraria extract showed more potential radical scavenging activities than those of mistletoe extract evaluated in both DPPH and NO test. Especially, the NO radical scavenging activity of pueraria extract ($SC_{50}$/, 88 $\mu$g) was comparable to that of vitamin C ($SC_{50}$/, 77 $\mu$g). Even pueraria extract possessed a much less reducing power compared to vitamin C, it also revealed higher reducing power than that of mistletoe extract. These results indicate that mistletoe extract and pueraria extract may serve as an useful natural antioxidant agents, and led to suggest the hypothesis that compounds having an antioxidant activity, i.e., radical scavenging activity or reducing power may be correlated with the downregulation of NF-$textsc{k}$B activation in human keratinocytes.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.170-178
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• 2001

Background: Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse peritoneal macrophages to produce interleukin $1{\beta}$ (IL-$1{\beta}$). Methods: Hemagglutination assay was carried out to examine whether M11C contained a lectin or not. To know the effect of M11C on the production of IL-$1{\beta}$, the macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated macrophages-conditioned media; MMCM). MMCM was analyzed for the IL-$1{\beta}$ quantification and mRNA expression by means of ELISA and RT-PCR, respectively. Results: Maximum effective dose and time of M11C on IL-$1{\beta}$ production from macrophages were $20{\mu}g/m{\ell}$ and 8 hours, respectively. This ELISA data was reconfirmed by immunoblotting assay. indicating that M11C is a good candidate for an immunomodulator. The dose and time dependent effects of M11C on the expression of IL-$1{\beta}$ mRNA from macrophages was also shown in expression of mRNA detected by RT-PCR. Treatment dose and time for the maximum expression of IL-$1{\beta}$ mRNA were $20{\mu}g/m{\ell}$ and 4 hours, respectively. Maximum gene expression of IL-$1{\beta}$ was much earlier than maximum production of it. Conclusion: As results, Korean mistletoe extract, M11C, may be used for an immunomodulator. This will be able to make up for and solve the problems caused by existent immunoagent with many adverse effects through many other studies in future including one molecule extraction.

• Journal of Pharmacopuncture
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• v.18 no.1
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• pp.7-18
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• 2015

Objectives: Loranthus ferrugineus (L. ferrugineus) from Loranthaceae, a mistletoe, is a medicinal herb used for a variety of human ailments. Traditionally, decoctions of this parasitic shrub have been mainly used to treat high blood pressure (BP) and gastrointestinal complaints; usage which is supported by experimental based pharmacological investigations. Nonetheless, there is still limited data available evaluating this plant's traditions, and few studies have been scientifically translated toward evidence based phytomedicine. We therefore provide a concise review of the currently available L. ferrugineus literature and discuss potential directions for future areas of investigation. Methods: We surveyed available literature covering ethnopharmacological usage of L. ferrugineus and discussed relevant findings, including important future directions and shortcomings for the medicinal values of this parasitic shrub. Results: Evidence based pharmacological approaches significantly covered the medicinal application of L. ferrugineus for hypertension and gastrointestinal complaint management, with a particular focus on the active hydrophilic extract of this herb. Conclusion: Understanding the sites of action of this plant and its beneficial effects will provide justification for its use in old traditional treatments, and potentially lead to the development of therapies. Other medicinal applicative areas of this parasitic shrub, such as wound healing, gerontological effects, and antiviral and anticancer activities, are yet to be researched.

• Food Science and Preservation
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• v.18 no.1
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• pp.72-78
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• 2011

The physiological properties of oak mistletoe slice extracts were investigated. The total polyphenol content of mistletoe extracts was 50.28-109-69 mg%, depending on extraction conditions. The polyphenol content increased as extract concentration rose (25 mL/g>50 mL/g>100 mL/g). The electron-donating ability (EDA) of the 60% (v/v) ethanolic extract was 68.88% at 25 mL/g; this was the highest value of all extracts tested (p<0.05). The SOD-like activities of water, 30%, 60%, and 90% (all v/v) ethanolic extracts were 15.24-30.84% lower than those of 1.0% and 0.1% (both w/v) L-ascorbate solutions. Tyrosinase inhibitory activities of all samples were 3.40-30.92% lower than those of 1.0% and 0.1% (both w/v) L-ascorbate solutions. Nitrite-scavenging abilities measured at pH 1.2 and pH 3.0 were highest when the water, and the 30%, 60% and 90% (all v/v) ethanolic extracts, were tested. The results expand our understanding of the physiological properties of oak mistletoe slice extracts.

• Korean Journal of Food Science and Technology
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• v.29 no.2
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• pp.362-368
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• 1997

As a preliminary study for the development of cancer-preventing functional food using Korean mistletoe, the cytotoxic effects of Korean mistletoe on between non-tumorigenic A3l cell and tumorigenic MSV cell derived from mouse 3T3 fibroblast cell line were investigated. While the raw extract, of which $ID_{50}$, value was $3.94\;{\mu}g/mL$, showed strong cytotoxic effect, its heat-treated extract was not cytotoxic up to $30\;{\mu}g/mL$. On the other hand, the heat-treated extract with law concentration showed an accelerative effect on the proliferation of non-tumorigenic A3l cell and an inhibitory effect on that of tumorigenic MSV cell. In addition, the influences of the addition of carbohydrates, such as galactose, lactose, glucose, mannose, fructose, sucrose and starch, to mistletoe extract were studied. There were not any significant changes with raw extract plus carbohydrate treatment, but the accelerative and inhibitory effects of heat-treated extract on each A3l and MSV cell were increased further by the treatment with sugars such as lactose, galactose, glucose, fructose. In order to investigate the changes of cytotoxicity of fermented Korean mistletoe according to fermentation periods, the raw and heat-treated extract were inoculated with Lactobacillus plantarum. During 1, 3, 5 and 7 fermentation days, the fermented raw mistletoe extract showed gradual accelerative effect on A31 cell proliferation without any changes of cytotoxicity on MSV cell. In case of the fermented heat-treated extract, however, the accelerative effect of heat-treated extract on A31 cell proliferation in early stage was disappeared during the fermentation.