Korean mistletoe has a variety of biological effects, such as immunoadjuvant activities. This study investigates the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on human T lymphocytes to determine whether VCA acts as an immunomodulator. Purified human T-lymphocytes were cultured with VCA and RNA from each point was analyzed using Affymetrix human genome chips containing 22,500 probe sets which represents more than 18,000 transcripts derived from 14,500 human genes. As a result, there was a striking upregulation of genes coding for chemokines. Seventeen genes out of 50 coding for proteins with chemokine activity were upregulated including CXCL9 and IL-8 which are related to the treatment of cancer. In addition, 28 cytokine genes were upregulated including IL-1, IL-6, IL-8, IFN-$\gamma$, and TNF-$\alpha$. Taken together, the data suggest that Korean mistletoe lectin, in parallel with European mistletoe, has an ability to modulate human T cell function.
The inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum), on tumor metastases produced by highly metastatic murine tumor cells, B 16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, was investigated in syngeneic mice. (omitted)
In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.
This study was conducted to study the seasonal changes of relative water relations parameters by pressure-volume curves of Korean mistletoe (Viscum album var. coloratum) leaves for understanding ecological characteristics. In growing season, the osmotic potentials at full turgor (${\Psi}_o^{sat}$) and at incipient plasmolysis (${\Psi}_o^{tlp}$) decreased, while increased the maximum bulk elastic modulus of the cell wall ($E_{max}$) and relavive water content ($RWC^{tlp}$). Korean mistletoe in Quercus variabilis and Korean mistletoe in Quercus mongolica in November showed best maximum perssure potential (${\Psi}_{P,\;max}$). Pressure potential (${\Psi}_P$) and water potential (${\Psi}_L$) in Korean mistletoe in Quercus variabilis were rapidly decreased with decreasing of relative water content. The values of $RWC^{tlp}$ in November were all above 84% showing that the function of osmoregulation is somewhat better, and symplastic water content (Vo/DW) and maximum water content (Vt/DW) were variable seasonally. Thus, responses to water relations of Korean mistletoe in Quercus variabilis and Korean mistletoe in Quercus mongolica such as ${\Psi}_o^{sat},\;{\Psi}_o^{tlp},\;E_{max},\;{\Psi}_{P,\;max},\;RWC^{tlp}$ showed increaing drought tolerance with increasing of leaf aging.
Effects of Korean mistletoe extracts (KM-110), Viscum album coloratum on the specific and non-specific immune responses of Japanese eel Anguilla japonica were examined. The optimal concentration not showing toxicity of KM-110 was determined to $30-40{\mu}g/ml$ in vitro and $100{\mu}g$/100 g of fish in vivo. Even $1000{\mu}g$ of KM-110/100 g of fish did not show any clinical problem in fish though the levels of toxic parameters were slightly increased. In terms of antibody production, KM-110 significantly elicited more antibody production than FCA or $\beta$-glucan. $\beta$-glucan plus KM-110 group synergistically enhanced antibody production. There was no significant difference between KM-110 and KM-110 plus $\beta$-glucan group. The ROI production by head kidney (HK) leucocytes of eel injected with 500 or $1000{\mu}g$ KM-110 was significantly (P<0.05) enhanced than the control and FCA-treated group. Maximum increase in the NBT reduction value was observed in $1000{\mu}g$ KM-110 group but no significant difference was found between 500 and $1000{\mu}g$ KM group. The level of serum lysozyme activity was significantly (P<0.05) higher in the 500 and $1000{\mu}g$ KM-110- or FCA-treated group than in the control and $200{\mu}g$ KM-110 group. The phagocytic activities of HK leucocytes isolated from eel injected with 500 and $1000{\mu}g$ KM-110 were significantly (P<0.05) higher than $200{\mu}g$ KM-110 and PBS-injected control group. Korean mistletoe appeared to be a good activator of the specific and non-specific immune responses of Japanese eel.
Park, Jong-Heum;Ji, Seung-Taek;Hyun, Chang-Kee;Chin, Koo-Bok;Shin, Heuyn-Kil
Korean Journal of Food Science and Technology
/
v.32
no.2
/
pp.461-468
/
2000
To investigate the antigenotoxicity of Korean mistletoe using Comet assay, the crude extract was divided into 4 fractions, i.e. fraction I (MW range over 14,000), fraction II $(8,000{\sim}14,000)$, fraction III $(3,500{\sim}8,000)$, and fraction IV (below 3,500) by molecular weight fractionation. In the non-tumoral 3T3 cells, fraction IV could reduce DNA damage induced by MNNG in a dose dependent pattern while fraction I and III which were known to contain lectins and viscotoxins, respectively, did not show the activity. By heat treatment, the antigenotoxic activity of faction IV, though was gradually diminished according to heating time, was found to be maintained significantly. From the Sephadex G-25 gel filtration chromatography, a more purified fraction responsible for the activity of faction IV was obtained from the latter part of total elute. Therefore, it was concluded that the antigenotoxic components of Korean mistletoe were water soluble substances of MW below 1,000 and there is a possibility of utilization as a material of functional foods for chemoprevention.
The copper-containing enzyme, tyrosinase, catalyzes the oxidation of tyrosine into dihydroxy phenylalanine (DOPA) and subsequently DOPAquinone. It is responsible, not only for the pigment melanin biosynthesis in human skin, but also for browning in foods. In the present study, tyrosinase inhibitory and antioxidant activities of Korean mistletoe extract and its fractions were investigated. As a result, both water and methanol (MeOn) extracts inhibited the tyrosinase activity. Among the fractions, the fraction eluted with $95\%$ MeOn significantly inhibited the tyrosinase activity. The fraction was further purified, and the purified fraction C strongly inhibited the enzyme activity up to $92\%$. In addition, water and methanol extracts exerted radical scavenging effects. The fractions eluted with $70\%\;MeOn\;and\;95\%$ Me on showed high radical scavenging activities. In conclusion, these results suggest that Korean mistletoe extract and its fractions might be useful for the treatment of various dermatological disorders such as epidermal hyperpigmentation and for improving food quality.
Objectives: The objective of this study is Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) to experimental prove comparative study of VCA and BV on the anti-cancer effect and mechanisms of action. Methods: In this study, it was examined in a human hepatocellular carcinoma cell line, Hep G2 cells. Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro. VCA and BV killed Hep G2 cells in a time- and dose-dependent manner. Results: The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action was examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including SAPK/JNK, MAPK and p38. BV also activated PARP-1, MAPK, p38 but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. Conclusion: We examined the involvement of kinase in VCA or BV - induced apoptosis by using kinase inhibitors. VCA-induced apoptosis was partially inhibited by in the presence.
Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.
This study was designed to develop microencapsulated Korean mistletoe extract, to determine the stability in vitro and to examine its application in milk. Coating materials used were polyglycerol monostearate (PGMS) and medium-chain triacylglyderol (MCT). The highest efficiency of microencapsulation was 78.3% with 15:1:40 (w/w/v) as PGMS : mistletoe extract : distilled water and 66.1% with 15:1 (w/w) as MCT : mistletoe extract. The size of microcapsule was about 30.0 and $19.5{\mu}m$ with PGMS and MCT, respectively. When microcapsules of mistletoe extract were incubated in simulated gastric fluid at pH 2 for 60 min, 14.8 and 17.2% of lectin was released from capsules which were coated with PGMS and MCT, respectively. Comparatively, 83.2 and 87.3% of lectin was released in simulated intestinal fluid (pH 8) after 60 min incubation of capsules coated with PGMS and MCT, respectively. The subsequent study determined the changes of physicochemical and sensory characteristics of milk with fortification of the mistletoe extract microcapsules during 12 day storage. TBA value was significantly lower in microcapsule-added groups than in the uncapsulated mistletoe extract-added group during the storage. When 100 ppm microencapsulated mistletoe extract was added, the L-, a- and b- values and viscosity were not significantly different from those of the control. In addition, the release of lectin from mistletoe extract over 12 days was 8.3 and 9.5 mg/100 ml in milk containing microcapsules made by PGMS and MCT, respectively. All sensory attributes showed a significant difference in uncapsulated mistletoe extract-added milk compared with other groups. The present study indicated that microcapsules of Korean mistletoe extract could be applied to milk and microcapsules coated with PGMS were effectively released in a simulated intestinal environment.
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