Effect of Korean Mistletoe (Viscum album Coloratum) on the Non-Specific Immune Responses in Japanese Eel (Anguilla japonica)

Cho, Young-Hye,Choi, Dae-Han,Choi, Sang-Hoon The Korean Society of Fish Pathology 2005 한국어병학회지 Vol.18 No.1

In the present paper, the immunostimulatory effects of Korean mistletoe (Viscum album Coloratum) on the non-specific immune responses of Japanese eel (Anguilla japonica) were examined. Eel were innoculated with mistletoe, Freund's complete adjuvant (FCA), or phosphate-buffered saline (PBS) as a control into their peritoneal cavities. The number of nitrobule tetrazolium (NBT)-positive cells in the head kidney of fish was significantly increased by the second day post-injection of mistletoe. ROI products were more enhanced in mistletoe-injected fish kidney leucocytes than in FCA-injected ones. The level of lysozyme activity detected in the serum of fish 2 days after injection with mistletoe was also significantly higher than that found in the serum of the control fish. The appropriate concentration of mistletoe to induce the highest level of serum lysozyme activity was revealed to 1000${\mu}g$/200 g of fish. In phagocytic activity assay, mistletoe-sensitized eel kidney phagocytes captured more zymosan than did the control fish. Korean mistletoe appeared to be a good activator of the non-specific immune responses of Japanese eel.

RE-17 : Effect of Mistletoe on Activity of NK cell in Endometriosis

정인철,남궁정,송재연,조현희,김장흡,김미란 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

The purpose of this study is to investigate the effect of mistletoe on NK cell cytotoxicity and its mechanism of action on NK cells in the endometriotic peritoneal fluid. NK cell line was incubated in peritoneal fluids from women between 20 and 40 years of age (divided into two groups according to the disease stage: stage 1 & 2 - group A, stage 3 & 4 - group B) who underwent laparoscopic surgery from January 2011 to December 2011, and the cytotoxicity of NK cells against target cells (K562 cells) was evaluated. The cytotoxicity of NK cells before mistletoe treatment was compared with the cytotoxicity of NK cells after mistletoe treatment, and the effect of mistletoe on NK cell apoptosis was evaluated. In addition, the expression of CD107a, which directly participates in exocytosis of cytotoxic granules, was compared. The cytotoxicity of NK cells showed a significant difference between the control peritoneal group, the endometriosis group A and group B (75.55%, 69.59% and 63.8%, respectively). The cytotoxicity of NK cells was diminished according to the stage of endometriosis (p=0.032). The cytotoxicity of NK cells before and after treatment with 200 ng/ml mistletoe was 81.64% vs 87.75% (p=0.012) in the control peritoneal fluid group, 78.30% vs 86.40% (p=0.003) in the endometriosis group A, and 73.67% vs 84.54% (p=0.024) in group B, respectively. No significant difference was observed between NK cell apoptosis before treatment with mistletoe and NK cell apoptosis after treatment with mistletoe in all groups; 1.94% vs 1.93% in the control peritoneal fluid group, 1.74% vs 1.77% in group A, and 1.49% vs 1.27% in group B (p=0.373). The expression of CD107a was significantly increased in each group after mistletoe treatment. The expression of CD107a before and after mistletoe treatment was 0.70% vs 1.67% (p=0.012) in the control peritoneal fluid group, 0.59% vs 1.10% (p=0.002) in group A, and 0.79% vs 1.40% (p=0.014) in group B, respectively. Mistletoe directly influenced exocytosis of cytotoxic granules by increasing the expression of CD107a in NK cells, and consequently there was a recovery of cytotoxicity of NK cells. Therefore, it can be expected that mistletoe will be significantly effective in the treatment of endometriosis

MISTLETOE (Viscum album var. coloratum) Growing on Carpinus laxiflora BL. Induces the Differentiation of Human Acute Promyeocytic Leukemia (HL-60) Cells

Sang-Cheol Kim,Soo-Young Park,Jae-Hee Hyoun,Hee-Yeong Cho,Young-Jae Lee,Ji-Hoon Kang,Young-Ki Lee,Doek-Bae Park,Eun-Sook Yoo,Hee-Kyoung Kang 한국독성학회 2004 Toxicological Research Vol.20 No.4

The present study was undertaken to investigate the effects of mistletoe (Viscum album var. coloratum) growing on Carpinus laxiflora BL. on proliferation and differentiation of HL-60 acute promyelocytic leukemia cells. Aqueous extract and its (NH₄)₂SO₄ saturated fractions of the mistletoe exhibited potent anti-proliferation activity against HL-60 cells. Moreover, when HL-60 cells were treated with 0~30% and 30~70% (NH₄)₂SO₄ saturated fractions of the mistletoe, HL-60 expressed CD 66b or CD 14 cell surface antigens and showed activity to reduce nitroblue tetrazolium, indicating that mistletoe induces the differentiation of HL-60 into granulocytes or monocytes. To understand how mistletoe induces the differentiation, we investigated the expression of molecules for modulating the proliferation and differentiation of leukemia cells, such as c-Myc and myeloblastin. The 0~30% (NH₄)₂SO₄ saturated fraction of the mistletoe reduced the mRNA levels of c-Myc and myeloblastin in a time-dependent manner. The results indicate that the mistletoe induces the differentiation of HL-60 cells via the decrease of c-Myc and myeloblastin expressions. Thus, it is suggested that mistletoe has a therapeutic potential for the treatment of acute promyelocytic leukemia.

Mistletoe lectin I/D-galactose의 인식결합에 기초한 Mistletoe lecti I에 대한 용액상 효소결합분석법에 관한 연구

이인숙,이은아,전종순,Rhee Paeng, Insook,Lee, Eun Ah,Chon, Chong Soon 한국분석과학회 2000 분석과학 Vol.13 No.5

Mistletoe lectin I(ML I)에 대한 간단하고 빠른 용액상 효소결합 분석법을 렉틴의 당 특이성을 이용하여 개발하였다. ML I에 특이성을 가지고 있는 D-galactose를 사용하였으며, 용액상 분석법의 효소로는 malate dehydrogenase(MDH)를 사용하였다. 분석신호물질로 사용되는 MDH-galactose 접합체는 isothiocyanate 방법을 통해 합성하였으며, 이 접합제는 thiourea 결합을 하고 있다. ML I의 존재하에, ML I은 D-galactole와의 특이 인식결합을 통해 MDH-galartose 접합체의 활동도를 억제한다. 그러므로, 존재하는 ML I의 농도는 MDH-galactose 접합제의 촉매활동도의 억제도에 비례하게 된다. 따라서, 본 용액상 효소결합 분석법을 통하여 ${\mu}g/mL$ 수준의 ML I의 측정이 분석 시간 10분 이내에 가능하였다. A simple and rapid homogeneous enzyme-linked binding assay for mistletoe lectin I(ML I) was developed using a coupled enzyme system of malate dehydrogenase (MDH) and D-galactose. A highly substituted MDH-galactose conjugate was prepared by employing an isothiocyanate method for formation of thiourea bond. In the presence of ML I, ML I inhibits the activity of the conjugate based on the ML I/D-galactose specific interaction. Thus, the concentration of ML I can be related to the homogeneous inhibition of the MDH-galactose conjugate. Using this method. ML I can be measured at the level of microgram per milliliter within 10 minutes.

S-363 Chemical pleurodesis using mistletoe extracts via spray catheter during medical thoracoscopy

( Sun Hack Lee ),( Jung Seop Eom ),( Tae Hwa Kim ),( Kyu Min Lee ),( Ji Yeon Shin ),( Han Na Lee ),( Bo Hye Song ),( Yong Ki Sim ),( Geewon Lee ),( Jeong Ha Mok ),( Hyo Yeong Ahn ),( Min Ki Lee ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

We present three cases of successful chemical pleurodesis with a liquid solution of mistletoe extract using a spray catheter during medical thoracoscopy. The medical thoracoscopy was performed in all presented cases to remove pleural effusion and conduct chemical pleurodesis to manage symptomatic malignant pleural effusion. A spray catheter was used to instill the mistletoe extract evenly into the pleural cavity, and there were no pleurodesis-related complications. Respiratory symptoms caused by pleural effusion improved after pleurodesis, and successful pleurodesis was maintained for more than 3 months after medical thoracoscopy in all three patients. Lee and Colt reported that instilling lidocaine via a spray catheter is effective for pain control before chemical pleurodesis during medical thoracoscopy. Using a spray catheter in the same way, we performed pleurodesis with a mistletoe extract via a spray catheter in three patients with MPE. A complete response, defined as no pleural effusion within 4 weeks after the last pleurodesis6, was achieved in all three patients. Several studies have used liquid mistletoe extract via a chest tube for chemical pleurodesis. Stumpf et al. reported that the overall response to mistletoe extract pleurodesis was 72% in 20 patients with MPE. Mistletoe extract, which was previously verified as an effective sclerosant for pleurodesis via a chest tube, could be evenly sprayed into the pleural cavity during thoracoscopy using a spray catheter. Distributing the sclerosant evenly into the pleural cavity with a spray catheter may lead to successful pleurodesis, particularly in patients who underwent medical thoracoscopy. In conclusion, We found that instilling the mistletoe extract using a spray catheter was an effective pleurodesis method and could possibly be performed as an alternative to talc poudrage.

Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

( Won Bong Park ),( Su Yun Lyu ) 한국응용약물학회 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.18 No.4

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-γ, and TNF-α. Taken together, the data suggest that Korean mistletoe lectin, in parallel with European mistletoe, has an ability to modulate human T cell function.

Korean Mistletoe Lectin-induced Apoptosis in Hepatocarcinoma Cells is Associated with Inhibition of Telomerase via Mitochondrial Controlled Pathway Independent of p53

Park, Won-Bong,Lyu, Su-Yun,Choi, Sang-Ho The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.1

The extract of European mistletoe ( Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coleratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisns for these effects. We showed that VCA induced atoptosis in both SK-Hep-1 and Hep 3B (p53-negative) cells through p53- and p21 -independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondria controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.

미슬토 추출물(Mistletoe Extract)이 위암환자의 수술 후 면역기능에 미치는 효과

양성우,신동규,김일명,윤성민,이용직,허수학,김태희,Yang, Sung-Woo,Shin, Dong-Gue,Kim, Il-Myung,Yoon, Seong-Min,Lee, Yong-Jik,Heo, Su-Hak,Kim, Tae-Hee 대한위암학회 2007 대한위암학회지 Vol.7 No.3

목적: 미슬토 추출물은 서양에서 오래전부터 사용되어진 면역치료 물질로 위암에 대해서는 연구가 부족한 실정이다. 본 연구에서 수술 받은 위암환자를 대상으로 항암제와 미슬토 추출물의 병합투여가 면역기능에 미치는 효과를 파악하기 위해 시행되었다. 대상 및 방법: 원발성 위암으로 진단받고 근치적 수술을 받은 10명의 환자를 선정하여 항암화학요법과 병행하여 수술 후 7일째부터 미슬토 추출물(ABNOVA viscum-Q)을 주 3회, 총 16주간 피하주사 하였다. 면역기능에 미치는 효과는 환자의 말초혈액에서 백혈구수와 그 분획, 백혈구에 대한 총림프구의 분율 그리고 시토카인들(Interleukin-$1{\beta}$, Interleukin-2, Interleukin-6, Interferon-$\gamma$, Tumor necrosis factor-$\alpha$)의 변화를 분석하였다. 상기 항목들은 수술 전과 수술 후 8주, 16주 총 3회 측정되었다. 결과: 남녀비는 9 : 1이며, 평균연령은 55.9세(range $33{\sim}74$세)였다. 병기는 stage Ib가 4명, II가 6명이었다. 백혈구수와 총호중구수는 기저치에 비해 치료 후 8주와 16주에 유의한 감소를 보였다. 총호산구수는 기저치에 비해 8주와 16주에 증가하는 경향을 보였지만 통계적 유의성은 없었다(P=0.15). 총림프구의 수치는 치료 전후 유의한 감소를 보이지만 백혈구 수에 대한 총 림프구의 분율은 유의하지는 않지만(P=0.91) 오히려 증가하고 있다. 각각의 시토카인들은 치료전후 큰 변화를 보이지 않았다. 결론: 치료 전후 의미있는 면역반응의 증가는 관찰하기 어려웠다. 이것은 미슬토 추출물과 항암제의 병용투여에 의한 면역활성과 억제의 상쇄반응으로 생각된다. 총호산구수가 증가하였고, 백혈구에 대한 림프구의 분율이 감소하지 않고 증가하는 양상을 보인 것은 미슬토 추출물에 의해 유발된 면역반응으로 생각된다. Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

F-61 Managing malignant pleural effusions with pleurodesis using mistletoe extract via a spray catheter during semi-rigid pleuroscopy

엄중섭,목정하,이민기,김미현,이광하,김기욱,박혜경 대한결핵 및 호흡기학회 2016 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.121 No.0

Background: Using a spray catheter, a liquid sclerosant, such as mistletoe extract, can be sprayed evenly into the pleural cavity for pleurodesis during semi-rigid pleuroscopy. We conducted a retrospective study of a prospectively collected database to identify the usefulness of pleurodesis using mistletoe extract via a spray catheter during semi-rigid pleuroscopy for symptomatic malignant pleural effusion (MPE). Methods: From October 2015 to September 2016, all consecutive patients with symptomatic MPE who underwent semi-rigid pleuroscopy were registered prospectively. The response was evaluated with chest X-rays or computed tomography 4 weeks after pleurodesis. Results: The study included 43 patients who underwent pleurodesis using mistletoe extract via a spray catheter. 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 (IQR, 6-8) days in the 40 patients with complete or partial responses. In 4 weeks after semi-rigid pleuroscopy, there were no cases of severe hemorrhage, empyema formation, respiratory failure, or procedure-related mortality in the study subjects. Conclusion: During semi-rigid pleuroscopy, pleurodesis with mistletoe extract via a spray catheter is a safe, effective procedure for managing symptomatic MPE.

Anti-Inflammatory Properties of Flavone di-C-Glycosides as Active Principles of Camellia Mistletoe, Korthalsella japonica

( Min Kyoung Kim ),( Kwang Jun Yun ),( Da Hae Lim ),( Jinju Kim ),( Young Pyo Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.6

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 mg/ 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.