• The Journal of Korean Medicine
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• v.25 no.4
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• pp.108-120
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• 2004

Objective : Euonymus alatus (Thunb.) Sieb (EA) is a traditional Korean herbal medicine, commonly used to treat tumors in Korea and China for centuries. Several earlier studies have indicated that EA exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of EA in a human uterine leiomyomal smooth muscle cell (ULSMC) line. Methods : This study was evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G1 cell analysis. Results : This study observed that EA treatment caused apoptotic cell death and depletion of intracellular glutathione (GSH) and that reduction of mitochondrial membrane potential was found to be involved in the initiation of apoptosis by EA. Conclusion : This results show that EA exerted clear cytotoxic effects and strongly inhibited the proliferation of ULSMC.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.3
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• pp.67-76
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• 2005

Purpose : 귀전우(Euonymus alatus, EA)는 현재까지 항종양활성을 나타낸다고 보고되었지만 그 작용 메커니즘에 대해서는 아직 밝혀지지 않은 채 남아 있다. 본 연구에서는, 자궁근종세포(ULSMC)에서 EA의 분자적 수준에서의 작용메커니즘을 연구${\cdot}$검토하고자 하였다. Methods : EA의 열수추출액이 자궁근종세포(ULSMC)와 caspase-3 pretense의 활성도에 미치는 영향을 측정하였다. Results : 우리는 자궁근종에서 EA 유도 세포독성의 메커니즘을 검토하였는바, 근종 세포들은 20-200g/ml 농도의 EA추출물에 6시간 배양될 때, caspase-3가 활성화되고, 그때 세포들은 apoptosis를 유발하게 되었다. EA에 의한 apoptosis의 유도가 진행되었으며, cytochrome- c의 세포질분획에서 양적증가가 caspase-3의 활성보다도 우세하였다. GSH합성의 저해제인 5mM buthionine용액에 전처리는 EA유도 apoptosis를 용이하게 하지만 pan-caspase inhibitor인 Z-VAD-fmk용액 전 처리는 부분적으로 apoptosis유도를 억제하였다. 한편, EA는 건강한 지원자들로 부터 채취한 말초혈액 단핵세포들에 있어서는 독성의 효과는 없었다. Conclusion : 이들 결과들은 EA가 prooxidant로 작용을 하고 그리고 caspase-3 activation과 mitochondrial pathway를 경유하는 apoptosis를 유발한다는 것을 나타낸다. EA의 탕제약제로서 열수추출액이 항산화활성뿐만 아니라, 종양세포에 대한 세포독성효과를 나타낸다고 보고된 바, 이에 향후 근종치료에 대한 임상연구가 필요할 것으로 보인다.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.213-220
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• 2001

Background: A previous study has shown that Euonymus alatus (EA) has an antidotic activities against inflammation, suggesting possibility that EA can exert this beneficial effects to liver injury by an initial protection against drug-induced hepatocyte demage. The present study was undertaken to evaluate the protective effect of EA-extract on experimentally induced hepatitis in ICR mice and to investigate some mechanisms responsible for its action. Methods: Water EA extract was used in this experiments. The mice received i.p. a dose of 700 mg/kg galactosamine (GalN) together with $5{\mu}g/kg$ of endotoxin (LPS), or received i.v. 12 mg/kg of concanavalin A (Con A). EA (4 mg/mouse) was administrated on day -2, -1 and 0 before induction of liver injury. Liver injury was assessed by measurement of serum alanin amino-transferase (SGPT) levels on 9 hr after GaIN.LPS, or 8 hr after con A administration. Results: Treatment with either GaIN or LPS alone did not cause hepatitis. However, simultaneous administration of GalN and LPS to mice resulted in LPS-dose dependent fulminant hepatitis. GaLN/LPS-induced liver injury was reduced when mice were given EA for 3 days before induction. This preventive effect of Ea was more prominent when EA was given by intraperitoneal route rather then by oral route. Pretreatment of EA or dexamethasone inhibited significantly $TNF{\alpha}$ production in GalL/LPS-injured mice. However, EA-treatment did not influence $TNF{\alpha}$-induced hepatitis in GalN-sensitized mice, suggesting that $TNF{\alpha}$ is likely to act as one of final mediators of endotoxin action and the protective effect of EA might be manifested chiefly by inhibition of endotoxin-induced $TNF{\alpha}$ production, not by blocking the $TNF{\alpha}$-action. Injection of Con A into mice evoked remarkable liver injury in a dose dependent fashion. This liver damage was reduced by EA-pretreatment. Dexamethasone significantly reduced both GalL/LPS-induced and Con A-induced liver damages, showing synergism with EA. However, indomethacin reduced only GalN/ LPS-induced hepatitis, not for Con A-induced hepatitis. Conclusion: These results led to the conclusion that EA may be able to contribute at least in part to prevent the drug-induced hepatotoxicity, and that its anti-hepatitis effects might be manifested directly by modulation of endogenous mediators, such as leukotriese D4, $TNF{\alpha}$ and free radical, and indirectly by regulation of immune mediated responses. Also these results suggested that EA could be developed as a potential antidotic agent.

• YAKHAK HOEJI
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• v.48 no.4
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• pp.247-253
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• 2004

We investigated the hypoglycemic effect of formula containing Euonymus alatus (EA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin (STZ)-induced diabetic rats. In order to iduce hyperglycemic state 25 mg/kg of STZ was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 250 mg/kg of EA and 250 mg/kg of MF (E1Ml), or 500 mg/kg of EA mixed with same dose of MF (E2M2) for 3 weeks. Blood glucose levels and body weights were measured every 5th or 6th day. E1Ml and E2M2 both significantly reduced food intake, water intake, and fasting blood and urine glucose levels as compared to those in diabetic control group in a dose dependent manner. Body weight in diabetic control group was increased slightly after 3 weeks. Treatment group, however, showed gradual increase in body weights during 3 week-period. While plasma insulin levels of the diabetic control group were decreased to the level of 387$\pm$14 pg/ml from 534$\pm$36 pg/ml, those levels in E1Ml and E2M2-treated groups were both markedly increased by 13% and 26%, respectively. Urine glucose levels in E1Ml and E2M2-treated groups were also remarkably reduced by 17 and 26% compared to the levels of diabetic control group. While expression of membrane-bound glucose transporter-4 (GLUT-4) protein in skeletal muscle was reduced by 45% in diabetic control compared to the normal control, GLUT-4 protein expressions in E1Ml and E2M2-treated groups were augmented by 2 and 3.5 times compared to the diabetic control, respectively. Pancreatic HE staining experiments showed that E2M2-treated group revealed much less infiltrated mononuclear cells, indicating that E2M2 efficiently blocked insulitis induced by multiple low dose streptozotocin. Taken together, we conclude that formula containing EA and MF may prevent or delay the development of hyperglycemia through overexpression of GLUT-4 protein in skeletal muscle and prevention of insulitis.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.1-9
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• 2005

Purpose : 이 연구는 SKBR3 인간 유방암 세포주에 대한 Euonymus alatus (Thunb.) Sieb 추출물 (CWE) 의 증식억제, 항산화 작용 및 세포사 유발 효과를 검토하기 위해 이루어 졌다. Methods : SKBR3 세포주는 48시간 동안 다양한 농도 ($0-40\;{\mu}g/ml$)의 CWE를 첨가하면서 배양되었고, 세포의 생존 비율은 MTT 배양을 통해서 평가하였다. 또한 CWE의 증식억제 효과는 유방암 세포주의 세포사와 관련되어 있음을 형태학적인 변화와 올리고뉴클레오솜 DNA 분절을 통해 확인하였다. Results : CWE의 50%에서 효과를 나타내게 하는 약물농도인 $ED_{50}$ (effective dose 50%)은 $9.3+2.2{\mu}g/ml$이며, 약물의 농도에 의존하여 세포의 증식을 억제시켰다. 아울러, 다양한 농도와 배양시간에서 CWE가 ROS 생산을 억제하는 것을 밝힐 수 있었다. 따라서 이러한 작용과 항암예방효과는 농도와 노출 시간에 의존하였다. Conclusion : 이러한 관찰을 통해 Euonymus alatus (Thunb.) Sieb의 열수 추출물은 SKBR3 인간 유방암 세포주에 대해 강한 증식억제 효과와 강력한 항산화효과 및 세포사의 유발 효과를 가지는 것으로 인식할 수 있다.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.26-36
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• 2005

Objective : Many traditional herbal remedies exhibit several beneficial effects including anti-inflammation. Euonymus alatus (Thunb.) Sieb (EA), known as Gui jun woo in Korea, has long been used in folk medicine to regulate Qi (bodily energy) and blood circulation, relieve pain, eliminate stagnant blood, and treat dysmenorrhea in oriental countries. The exact mechanism of the anti-inflammatory action of Euonymus alatus (Thunb.) Sieb (EA), however, has not been determined. Methods: Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of EA could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RA W264.7 cells. Results: Stimulation of the peritoneal macrophages and RAW264.7 cells with $interferon-\gamma\;(IFN-\gamma)$ and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of EA barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RA W264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the MeOH and BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with $IFN-\gamma$ and LPS. Conclusion: Collectively, these results demonstrate that the MeOH and BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

• The Journal of Korean Medicine
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• v.22 no.2
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• pp.53-63
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• 2001

This study was carried out to investigate the physiological activityof the water extract from EA. The present study was done to investigate the effects of EA on cultured hepatocyte cell system and lipid peroxidation in $A{\beta}$ treatment conditions. Pretreatment of EA attenuated in cell cytotoxicity enhanced by increasing concentrations of $A{\beta}$. MDA level induced by $A{\beta}$ treatment was significantly increased and the level was slightly reduced by pretreatment of EA. The ability of EA to reduce cell death and MDA level induced by $A{\beta}$ suggest that EA may be a protective agent against free radical generating compounds such as $A{\beta}$. EA exhibited anti oxidative activity at all concentration tested.The extract was as good as antioxidative activity of the synthetic antioxidants, butylated hydroxy toluene and ascorbic acid. Furthermore, this was superior to that of natural antioxidant, a-tocopherol. In the presence of heavy metal ions ($Fe^{2+},{\;}Zn^{2+}$), EA showed strong antioxidative activity. The extracts showed about 3075% in the nitrite scavenging effect under pH 1.2 and $37^{\circ}C$ for 1 hr. There was significant difference among concentration of extracts.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• Korean Journal of Food Science and Technology
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• v.37 no.6
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• pp.898-904
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• 2005

Although Euonymus alatus (EA) has been used as traditional medicine for cancer treatment, exact substances involved in curing of the disease are not yet known. Free radical scavenging and reactive oxygen species (ROS) removal activities of aqueous extract components isolated from winged stem of EA in animal cell line were investigated. Aqueous extract of EA (AEEA) was fractionated by ultrafiltration. All fractions mainly consisted of polysaccharide (44.8%), protein (2.1%), small amounts of phenol compounds and organic acids. Antioxidant activity of AEEA increased depending on concentration fractions, as determined by 1,1-diphenyl-2-picrylhydrazyl method. ROS removal activity was visualized in Chinese hamster ovary cell line using laser scanning confocal microscope, and AEEA activity increased in order of F IV>F III>F I>F II. These results suggest AETA has bioactive carbohydrates with potentials as functional foods and antioxidants.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.5
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• pp.592-599
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• 2017

This study examined the nutritional compositions of seven raw and blanched green vegetables: Amaranthus mangostanus L. (AM), Aster scaber Thunberg, Taraxacum platycarpum H. Dahlstedt (TP), Oenanthe javanica (Blume) DC, Allium tuberosum Rottler, Ligularia fischeri (Ledeb.) Turcz (LF), and Euonymus alatus (Thunb.) Siebold (EA). Proximate compositions (moisture, protein, ash, dietary fiber, and fat), minerals (calcium, phosphorus, iron, potassium, sodium, and magnesium), and vitamins (riboflavin and vitamin C) were analyzed in the study. In this study, moisture contents of raw and blanched green vegetables were 71.28~92.68 g/100 g and 76.90~92.09 g/100 g, respectively. The protein and fat contents of raw LF (33.38 g/100 g and 4.50 g/100 g dry weight basis, respectively) were higher than those of other cultivars. Ash contents of AM were significantly higher than those of their respective raw samples. Potassium, magnesium, calcium, and sodium contents of AM were 7,710.63 mg/100 g, 1,786.67 mg/100 g, 1,534.44 mg/100 g, and 743.18 mg/100 g, respectively. In the case of raw green vegetables, iron content of TP was 55.23 mg/100 g, which was the highest value among tested green vegetables. Total dietary fiber content of EA was 59.75 g/100 g, which was the highest value. Riboflavin content was highest in the raw and blanched LF (3.10 mg/100 g and 3.05 mg/100 g, respectively). Vitamin C contents of raw and blanched EA were 468.28 mg/100 g and 471.42 mg/100 g, respectively, which were higher than the other values. There were differences in nutritional ingredients according to different types of green vegetables. Therefore, it is advisable to evenly ingest various green vegetables.