• The Journal of Korean Medicine
• /
• v.25 no.4
• /
• pp.108-120
• /
• 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
• /
• v.18 no.4
• /
• pp.1-9
• /
• 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
• /
• v.26 no.1 s.61
• /
• pp.26-36
• /
• 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 Obstetrics and Gynecology
• /
• v.18 no.3
• /
• pp.67-76
• /
• 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.

• YAKHAK HOEJI
• /
• v.48 no.4
• /
• pp.247-253
• /
• 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 Medicine
• /
• v.22 no.2
• /
• pp.53-63
• /
• 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.