Korean Mistletoe Research Articles

Antitumor Effect of KML-B-Treated Dendritic Cells via Induction of Lymphocyte Activation.

Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs. Additionally, matured DCs by KML-B induced T helper (Th) cell activation and differentiation toward Th1 cells. However, the interaction of KML-B-treated DCs with CD8+ T cells is still poorly understood. In this study, we confirmed the ability of matured DCs by KML-B to stimulate cytotoxic T cells using OT-1 mouse-derived CD8+ T cells. KML-B induced MHC I expression in DCs, stimulation of CD8+ T cell activation and proliferation, and IFN-γ secretion. Moreover, tumor sizes were reduced by KML-B treatment during vaccination of OVA257−264-pulsed DCs. Here, we confirmed induction of CD8+ T cell activation and the antitumor effect of KML-B treatment in DCs.

In vitro Anti-Tyrosinase Activity of Viscumneoside III and Homoflavoyadorinin B Isolated from Korean Mistletoe (Viscum album)

Various bioactive substances are found in mistletoe, including viscumneoside III (1) and homoflavoyadorinin B (2), both which inhibit tyrosinase. These two compounds are mainly found in the EtOAc fraction of the mistletoe extract and demonstrate higher rates of tyrosinase inhibition than ascorbic acid, which was used as a control. Our results suggest that mistletoe extracts can be utilized in skin whitening cosmetics.

A combination of Korean mistletoe extract and resistance exercise retarded the decline in muscle mass and strength in the elderly: A randomized controlled trial

Given the increased concerns about the degenerative decline in the physical performance of the elderly, there is a need for developing effective strategies to suppress the age-related loss of skeletal muscle mass and functional capacity through a lifestyle intervention. This randomized controlled trial examined whether a combination of Korean mistletoe extract (KME) supplement and exercise affected muscle mass, muscle function, and targeted molecular expressions. Sixty-seven subjects aged 55–75years were assigned to placebo, low-dose (1g/d), or high-dose (2g/d) of KME for 12weeks. The body composition was significantly changed in the high-dose group during the intervention period as determined by skeletal muscle mass (P=0.040), fat free mass (P=0.042), soft lean mass (P=0.023), skeletal muscle index (P=0.041), fat-free mass index (P=0.030), percent body fat (P=0.044), and fat mass to lean mass ratio (P=0.030). Knee strength was measured by Cybex, demonstrating a significant effect in the KME groups compared to the placebo group (P=0.026 for peak torque and P=0.057 for set total work), which was more pronounced after adjusting for age, gender, protein, and energy intake (P=0.009 for peak torque and P=0.033 for set total work). The dynamic balance ability was remarkably improved in the high-dose group over a 12-week period as determined by Timed “Up and Go” (P=0.005 for fast walk test and P=0.024 for ordinary walk test). Consistent with these results, RT-PCR, multiplex analyses, and immunocytofluorescence staining revealed that a high-dose KME supplementation was effective for suppressing intracellular pathways related to muscle protein degradation, but stimulating those related to myogenesis. In particular, significant differences were found in atrogin-1 mRNA (P=0.002 at a single administration and P=0.001 at a 12-week administration), myogenin mRNA (P<0.0001 at a single administration and P=0.040 at a 12-week administration), and insulin growth factor 1 receptor phosphorylation (P=0.002 at a 12-week administration). These results suggest that KME supplementation together with resistance exercise may be useful in suppressing the age-related loss of muscle mass and strength in the elderly.

A metabolomics approach to identify factors influencing their activity relative to oleanolic acid contents in Korean mistletoe types

The metabolite changes in Korean mistletoe, as functional food, and their effects on its biological activity were monitored. The Korean mistletoe species were successfully distinguished by hierarchical clustering analysis (HCA) in atmospheric-pressure chemical ionization (APCI) and electrospray ionization (ESI) mode. As shown by the PCA scatter plot and loading plot, the Santalaceae family exhibited significant markers derived from oleanolic acid, whereas the Loranthaceae family exhibited tentative markers derived from glycosidic derivatives of quercetin and kaempferol. The mistletoe extracts also inhibited plasminogen activator inhibitor 1 (PAI-1) differently depending on the mistletoe family. The Santalaceae family was shown to be a potent inhibitor of PAI-1, with an IC50 value of around 40.0 µg/mL. In contrast, the Loranthaceae family extracts did not inhibit PAI-1. Importantly, discrimination was shown across the chemotaxonomy of the plant, which correlated strongly with the oleanolic acid contents in Korean mistletoe.

Asian Elm tree inner bark prevents articular cartilage deterioration in ovariectomized obese rats with monoiodoacetate-induced osteoarthritis.

We investigated whether long-term consumption of Korean mistletoe or Asian Ulmi cortex would prevent or delay menopausal symptoms and progression of osteoarthritis in estrogen-deficient obese rats. Ovariectomized (OVX) rats were provided a 45% fat diet containing either (1) 0.6% lyophilized water extract of Korean mistletoe (KME) + 1.4% dextrose (KME; n = 10), (2) 2% lyophilized water extract of Ulmi cortex (UCE; n = 10), (3) 30 μg/kg bw 17β-estradiol + 2% dextrose (positive control; n = 10), (4) 2% dextrose (placebo; OVX-control; n = 10), or (5) 2% dextrose (normal-control; n = 10) for 4 weeks. At the beginning of the 5th week, OVX rats, except in the normal-control group, were given articular injections of monoiodoacetate into the right knee and the assigned diets were provided for an additional 3 weeks. The rats in the normal-control had injections of saline into the right knee. KME, but not UCE, partially prevented the insulin resistance and the loss of bone mineral density and lean mass. The limping scores were lower in the descending order of the OVX-control > KME and 17β-estradiol > UCE > normal-control at day 14 and 21 (P < 0.05). The scores for pain behaviors measured by weight distribution on the right leg, maximum running velocity on a treadmill and locomotive activity, were markedly decreased in the same order as limping scores. Monoiodoacetate increased the expression of matrix metalloprotinase-3 and metalloprotinase-13 in the articular cartilage and elevated the production of inflammatory markers such as tumor necrosis factor-α, interleukin-1β, and interleukin-6, but they were lower in the UCE than in the other groups (P < 0.05). Histology of the right knee revealed cartilage damage near the tidemark of the knee and proteoglycan loss was markedly less in UCE. UCE was an effective therapeutic agent for preventing osteoarthritis and KME prevented decreases in lean body mass, bone mineral density, and insulin sensitivity in estrogen-deficient rats.

Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol.

Viscum album var. coloratum (Korean mistletoe; KM) is an herbal medicine that is used worldwide for the treatment of various immunological disorders and cancers. KM extract showed enhanced anti-oxidative effects in 2,2-diphenyl-1-picrylhydrazyl, Trolox equivalent antioxidant capacity, and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester assays after being fermented with a crude enzyme extract from a soybean paste fungus, Aspergillus kawachii. High-performance liquid chromatography analysis showed four increased peaks in enzyme treated KM. The increased peaks were isolated and identified as caffeic acid (1), hesperetin (2), syringaldehyde (3), and lyoniresinol (4). Among the four compounds, only 1 and 4 showed strong anti-oxidative activity. Therefore, the fermentation increased the contents of 1 and 4, which consequently increased the anti-oxidative activity of KM.

The Impact of Environmental and Host Specificity in Seed Germination and Survival of Korean Mistletoe [Viscum album var. coloratum (Kom.) Ohwi

Humankind has been searching for medicinal materials from various plant sources in an attempt to treat disease. Mistletoe is one indubitable plant source for these materials due to its effectiveness in treating various diseases, but it has almost disappeared from the mountainous areas of Korea due to excessive harvesting. In this study, in order to select host tree species for Korean mistletoe [Viscum album var. coloratum (Kom.) Ohwi] by seed inoculation and to clarify the effect of host specificity among various tree species were conducted for the purpose of gaining basic information for the artificial cultivation of Korean mistletoe. Almost all the seeds of Korean mistletoe germinated in vitro at the temperature of 15℃. Among host trees used in this study, Prunus mume showed the highest parasitic affinity with inoculated Korean mistletoe, compared with any other host plants. However, treatment of hormones could not increase the low survival rate of Korean mistletoe on the host trees.

Studies on the Content of Lectin in Korean Mistletoe according to the Host Tree Species and Characterization for Its Application to the Quality Control

Studies on the Content of Lectin in Korean Mistletoe according to the Host Tree Species and Characterization for Its Application to the Quality Control

Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo.

In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit(®)) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric-coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8.

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.

한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과

본 연구에서는 C57BL/6J ob/ob 마우스를 이용하여 한국산 겨우살이 냉수 추출물(KME)의 항당뇨 활성을 조사하였다. 50 혹은 100 mg/kg의 KME를 1일 1회씩 경구투여 한 결과 KME 투여 개시 5일 후부터 ob/ob 마우스의 혈당이 유의하게 억제되었으며, 10일 후부터 안정된 억제 효과를 나타내고 대조군에 비해 20% 이상의 혈당강하 효과를 나타내었다. 경구 당부하 실험(OGTT)에서는 KME 경구투여 마우스에서 유효한 당부하 억제 활성이 관찰되었다. 또한 KME 경구투여는 ob/ob 당뇨 마우스의 혈액 내 총 콜레스테롤과 중성지질의 농도를 억제하는 것으로 나타났다. 한편 C2C12 근육세포를 이용한 in vitro 실험에서 KME를 처리함으로써 glucose uptake가 현저히 증가하였다. 한편 매우 흥미롭게도 KME를 처리한 C2C12 근육세포에 있어서 미토콘드리아 생성과 산화대사 조절물질인 peroxisome proliferatoractivated receptor gamma coactivator 1-α(PGC-1α)를 비롯하여 glucose transporter type 4(GLUT4), estrogen-related receptor-α(ERR-α), nuclear respiratory factor-1(NRF-1) 그리고 mitochondrial transcription factor A(TmfA)와 같은 PGC-1α 관련 유전자들의 발현이 증가하는 것으로 확인되었다. 이 결과는 KME가 2형 당뇨에 대한 치료물질로서의 작용을 지니며 이러한 KME의 항당뇨 활성은 미토콘드리아 생성의 조절과 관련 있는 것으로 추정된다.

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.

사료 내 홍삼박과 겨우살이 분말 첨가 급여가 육계의 생산성 및 계육의 품질에 미치는 영향

본 시험은 육계에 홍삼박과 겨우살이를 급여하여 5주간 사육한 육계의 생산성과 계육의 일반 성분, 혈액 성상, pH, TBARS, 보수성, 전단력 및 육색을 조사하였다. 실험구는 홍삼박과 겨우살이를 급여하지 않은 처리구를 대조구, 홍삼박 0.5% 급여구는 T1, 홍삼박 1% 급여구는 T2, 겨우살이 0.5% 급여구는 T3, 그리고 겨우살이 1% 급여구를 T4 등 4개 처리구로 나누어 사양하였다. 육계의 생산성은 처리구간 유의적인 변화는 없었고, 폐사율은 대조구보다 홍삼박과 겨우살이 급여구에서 낮아졌다(P<0.05). 계육의 수분, 조단백질 및 조회분 등의 일반 성분은 유의성이 없었으며, 조지방은 홍삼박과 겨우살이 급여구에서 낮았다. 육계의 혈액 성상 중 총 콜레스테롤과 LDL-cholesterol 함량은 대조구보다 홍삼박과 겨우살이 급여구에서 감소하였고, HDL-cholesterol은 증가하였으며, triglyceride와 glucose 함량은 유의한 변화가 없었다. TBARS는 대조구보다 홍삼박과 겨우살이 급여구에서 유의하게 낮아, 육계의 저장성 개선에 도움이되리라 생각된다. 육색은 CIE <TEX>$L^*$</TEX>값과 CIE <TEX>$b^*$</TEX>값은 홍삼박과 겨우살이 급여에 의한 변화는 없었지만, CIE <TEX>$a^*$</TEX>값은 T4에서 증가하였다. 결론적으로 홍삼박과 겨우살이를 급여하면 육계의 폐사율이 낮아지고, 총콜레스테롤과 LDL-cholesterol 함량이 감소하며, HDL-cholesterol이 증가함으로 혈액성상을 개선할 가능성이 있는 것으로 판단된다. The objective of this study was to evaluate the effects of different levels of red ginseng mare or Korean mistletoe powder on growth performance and physicochemical properties of thigh meat in broiler. A total of 200 broiler chicks were divided into five groups were fed a basal diet (control), basal diet supplemented with 0.5% red ginseng mare (T1), red ginseng mare 1% added (T2), Korean mistletoe 0.5% added (T3), Korean mistletoe 0.5% added (T4) for five weeks. Growth performance and proximate composition of chicken thigh meat were not influenced by all treatments, except for mortality and crude fat, which was significantly lower in all treatments with red ginseng mare or Korean mistletoe powder compared to control. Dietary red ginseng mare and Korean mistletoe supplementation had no significantly effects on pH, WHC, shear force, CIE <TEX>$L^*$</TEX>, <TEX>$b^*$</TEX> values, triglyceride and glucose but TBARS values total cholesterol, and LDL-cholesterol were decreased (P<0.05) by the addition red ginseng mare and Korean mistletoe powder. CIE <TEX>$a^*$</TEX> values increased significantly with added red ginseng mare and Korean mistletoe powder relative to the control (P<0.05). It was concluded that the addition of red ginseng mare and Korean mistletoe powder revealed minor improvements in the lipid oxidative stability of chicken meat.

The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats.

Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women.

Comparison of the effects of supplemental Korean mistletoe (Viscum album var. coloratum) powder and antibiotic on growth performance, serum cholesterol profiles, and meat quality of broilers

The effects of Korean mistletoe (KM) powder on the growth performance, serum cholesterol profiles, and meat quality of broiler chickens were assessed. A total of 150 male broilers (n = 30 birds/treatment) were randomly assigned to one of five groups (0.05% chlortetracycline or 0, 0.5%, 1%, or 2% KM). No significant differences were observed in growth performance, proximate composition of meat, and meat color, except for crude fat and L* values. The KM-treated groups showed significantly reduced serum cholesterol levels (but not high-density lipoprotein [HDL] cholesterol) as the amount of KM in the diet increased. Meat groups that received KM showed a decline in pH and thiobarbituric acid-reactive substances (TBARS) and an increase in total phenol and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging compared with the antibiotics and control groups. The addition of 1% and 2% KM at the optimal rate can help develop practical broiler diets and improve the antioxidant effects.

Synergistic anticancer effects of lectin and doxorubicin in breast cancer cells.

We studied the effects, either combined or alone, of lectin from Korean mistletoe (Viscum album var. coloratum agglutinin, VCA) and doxorubicin (DOX) in MCF-7 (estrogen receptor-positive) and MDA-MB231 (estrogen receptor-negative) human breast cancer cells. When VCA and DOX were combined, a strong synergistic effect was shown in cell growth inhibition, compared to VCA or DOX treatment alone. In quantitative apoptosis studies analyzed by flow cytometry, a combination of two agents showed an increase in apoptosis in both cells, compared to agents alone. Also, pro-apoptotic proteins including Bax, Bik, and Puma were increased in both cells, and the survival factor Bcl-2 was inhibited in MCF-7 cells when drugs were combined. Furthermore, VCA combined with DOX mediated S phase arrest, accompanied with a decrease of cell number at G0/G1 phase. This suggests that VCA and DOX combination may possibly lead to a novel strategy for the treatment of breast cancer.

Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML-B), a novel TLR4 agonist.

Korean mistletoe lectin (KML) is composed of A and B sub-chains. The B-chain binds to cell surfaces, whereas the A-chain hinders translation because it is a RIP (ribosome inactivating protein) inducing apoptosis. Although KML has various biological and immunological activities, its potential use in cancer therapy or as an adjuvant therapy is limited by its toxicity to normal cells. This study was conducted to determine whether the B-chain of KML (KML-B) has immunoadjuvant activity and cytotoxicity activity. To evaluate the immunomodulatory activities of B chain KML, in vitro experiments employing bone marrow-derived dendritic cells (BMDCs) were performed. Dendritic cells (DCs) are a unique group of white blood cells that are able to capture and process antigens for presentation to T cells, which constitute primary immune response. In the present study, KML-B was found to be non-cytotoxic to BMDCs. Furthermore, the expressions of co-stimulatory molecules (CD40, CD80, CD86, and MHC II) and the secretions of cytokines (IL-1β, IL-6, IL-12p70, and TNF-α) were increased in BMDCs by KML-B. In addition, other indicators (antigen-uptake and CCR7 expression) of BMDC maturation were changed by KML-B, and the ability of KML-B to enhance various functions by BMDCs was found to be dependent on TLR4 expression. Moreover, BMDCs matured by KML-B induced naïve CD4(+) T cell differentiation toward Th1 cells directly and indirectly. These experiments confirm that KML-B exhibits potent immunomodulatory properties and suggest that KML-B be considered a potential dendritic cell-based cancer therapy and immunoadjuvant.

The effects of Korean mistletoe extract on endurance during exercise in mice

Many investigators have screened drugs and foods for the enhancement of endurance capacity and antifatigue. Mistletoe, a semiparasitic plant on various deciduous trees, has many known biological activities, including anticancer, anti-diabetes, antioxidant, and anti-cardiovascular disease effects. In a previous study, Korean mistletoe extract (KME) was reported to increase endurance capacity in mice. However, whether the administration of KME further enhances exercise performance, when combined with exercise training, was not investigated. In this study, we demonstrate that the administration of KME decreases the level of plasma lactate dehydrogenase, parameter of tissue damage and muscle fatigue when combined with exercise training. Exercise training increases the muscular glycogen and plasma free fatty acid (FFA) level, and KME administration in sedentary mouse group increases the plasma FFA level, indicating that KME administration alters the energy resources in muscle. In addition, KME administration enhances the exercise performance in sedentary mouse group, but did not further enhance exercise performance when combined with exercise training, suggesting that KME could be an excellent mimetic of exercise.

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.