In this study, the effects of Sm addition (0, 0.05, 0.2, 0.5 wt%) on the microstructure, hardness, and electrical and thermal conductivity of Al-11Si-1.5Cu aluminum alloy were investigated. As a result of Sm addition, increment in the amount of α-Al and refinement of primary Si from 70 to 10 μm were observed due to eutectic temperature depression. On the other hand, Sm was less effective at refining eutectic Si because of insufficient addition. The phase analysis results indicated that Sm-rich intermetallic phases such as Al-Fe-Mg-Si and Al-Si-Cu formed and led to decrements in the amount of primary Si and eutectic Si. These microstructure changes affected not only the hardness but also the electrical and thermal conductivity. When 0.5 wt% Sm was added to the alloy, hardness increased from 84.4 to 91.3 Hv, and electric conductivity increased from 15.14 to 16.97 MS/m. Thermal conductivity greatly increased from 133 to 157 W/m·K.

본 연구에서 상동나무 가지 추출물(STB-E100)은 대장암 세포에서 세포사멸을 유도하여 세포생육을 억제하였다. 또한 Iκ B-α 인산화를 통한 IκB-α 단백질 분해를 유도하며 이로 인해 P65 핵내 전이를 유도하여 NF-κB 신호전달을 활성화시킨다. NF-κB 신호전달 활성화는 GSK3β 활성화를 통해 P65 핵내 전 이를 유도에 의한 것이지만 IκB-α분해는 GSK3β 의존성이 아니다. 상동나무 가지 추출물은 이러한 신호전달 활성화를 통해 세포사멸을 유도하여 대장암의 세포생육을 억제한다. 본 결과를 바탕으로 상동나무 가지가 암 예방 및 치료를 목적으로한 표적 요법에서 항암제 개발의 잠재적 활용 소재로서 이용 가능하다고 사료된다. 그러나 대장암 세포에서 상동나무 가지 추출물에 의해 유도된 NF-κB 신호전달 작용기전을 좀 더 구체적으로 구명할 필요가 있고 대장암에 대한 세포사멸과 작용기전의 정확한 관련성을 조사하기 위해 추가적인 연구가 필요하다.

이상의 연구 결과로 먹넌출 열매 추출물은 GSK3β 의존성 Cyclin D1 단백질의 분해를 통해 대장암세포의 생육 억제와 관련이 있는 것으로 확인된다. 본 결과는 대장암의 항암제 개발을 위한 소재로 먹넌출 열매의 활용이 가능할 것으로 판단된다.

이상의 연구 결과로 미루어 볼 때, 댕댕이나무 잎과 가지 추추출물은 대장암 세포주 HCT116과 SW480세포의 생육을 억제 하였으나 열매추출물은 억제활성이 나타나지 않았다. 잎과 가지 추출물은 cell migration과 wound healing assay를 통해 비정상적인 세포증식 억제를 확인하였으며, β-catenin과 TCF4 의 단백질 수준을 감소시켜 비정상적인 Wnt 신호전달을 억제를 통해 대장암세포의 생육을 억제하는 것으로 판단된다. 따라서 댕댕이나무 잎과 가지는 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다.

고령사회에서 노년기 건강의 큰 문제로 대두되고 있는 골다공증은 특히 폐경 후 여성들에게서 가장 그 발생빈도가 높게 나타났으며, 현재 골다공증 예방 및 치료에 사용되고 있는 약제는 대부분 골흡수 억제제로써 진행된 골소실을 회복 시킬 수는 없기 때문에 골형성 증가를 통한 골다공증 예방과 치료에 관한 연구가 활발히 이루어지고 있다. 산양삼(cultivated wild Panax ginseng, CWP)에 대한 연구는 다수가 원기회복, 자양강장 및 면역증강 효과 등에 대한 것이나 골대사에 미치는 영향에 대한 연구는 거의 없는 실정이다. 이에 본 연구에서는 산양삼 추출물이 조골세포에서 골관련 유전자 발현에 미치는 영향을 확인함으로써 골다공증 예방 및 치료 효과를 갖는 천연 소재로의 활용 가능성을 검토하고자 하였다. 산양삼 추출물 처리가 조골 세포 의 증식에 미치는 영향을 알아보기 위해 MTT assay를 실시하였고, MC3T3-E1 세포생존률은 FBS가 첨가되지 않은 배양액만 처리한 대조군과 산양삼 추출물을 처리한 실험군 모두에서 동일한 수준으로 나타났으며 이로써 산양삼 추출물의 안전성을 확인할 수 있었다. 또한 산양삼 추출물을 처리한 실험군과 대조군과의 세포증식률을 비교하였을 때 산양삼 추출물 50 ㎍/mL 농도 처리군에서 유의적으로 세포증식이 촉진되었으며 25 ㎍ /mL과 100 ㎍/mL 농도 처리군에서도 대조군보다 높은 경향을 나타내었다. 산양삼 추출물이 조골 세포의 활성에 미치는 영향을 알아보기 위해 조골세포의 분화초기 표지인자인 ALP 활성을 측정하였으며 그 결과 모든 산양삼 추출물 처리군이 대조군과 비교하여 유의적으로 높은 활성을 나타내었으며 특히 산양삼 추출물 50 ㎍/mL 농도 처리군에서 가장 높은 활성을 나타내었다. 산양삼 추출물의 농도에 따른 석회화 형성도를 확인하기 위해 무기질화된 세포의 기질을 alizarin red로 염색하였고 산양삼 추출물을 처리한 실험군과 대조군과의 석회화 형성도를 비교하였을 때 산양삼 추출물 50 ㎍/mL 농도 처리군에서 유의적으로 석회화 형성이 촉진되었으며 25 ㎍/mL과 100 ㎍/mL 농도 처리군에서도 대조군보다 높은 경향을 나타내었다. 산양삼 추출물이 MC3T3-E1 조골세포에서 골 형성 관련 유전자 발현에 미치는 영향을 확인하기 위해 Runx2, ALP, OPN, OCN 등의 유전자를 정량 real-time PCR을 통해 분석하였으며 대조군과 비교하여 모든 산양삼 추출물 처리군에서 농도 의존적이고 유의적으로 골 형성 관련 유전자발현이 증가되었다. 따라서 산양삼 추출물이 골 형성 관련 유전자인 Runx2, ALP, OPN, OCN 발현을 증가시켜 MC3T3-E1 조골세포의 분화를 촉진하고, 골 석회화 형성 촉진에 기여하였을 것으로 사료된다. 그러나 산양삼 추출물이 골형성과 관련하여 어떠한 기전으로 유전자의 발현을 조절하였는지에 대한 유전자 및 단백질 수준의 추가적인 연구와 산양삼 추출물의 분화 촉진과 석회화 형성능이 산양삼의 사포닌계 진세노사이드 성분의 영향인지에 대한 후속 연구가 필 요할 것으로 사료된다.

이상의 연구 결과로 미루어 볼 때, 도깨비부채 잎(RPL)은 β -catenin의 분해 유도를 통해 대장암, 유방암, 폐암, 전립선암 및 췌장암 세포의 생육을 억제하는 것으로 나타났다. 본 결과는 도깨비부채 잎의 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다. 그러나 추가적 연구를 통해 도깨비 부채 잎의 항암 활성물질의 분석연구가 필요할 것으로 사료된다.

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on β-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased β-catenin level in both protein and mRNA level. MG132 decreased the downregulation of β-catenin protein level induced by STB and STL. However, the inhibition of GSK3β by LiCl or ROS scavenging by NAC did not block the reduction of β-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate β-catenin protein level independent on GSK3β and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased β-catenin protein level, but not mRNA level in A549 cells. The downregulation of β-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated β-catenin protein, the inhibition of GSK3β by LiCl did not blocked the reduction of β-catenin by TY-NS-B. In addition, TY-NS-B decreased β-catenin protein in A549 cells transfected with Flag-tagged wild type β- catenin or Flag-tagged S33/S37/T41 mutant β-catenin construct. Our results suggested that TN-NS-B may downregulate β- catenin protein level independent on GSK3β-induced β-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

Background : Although the inhibitory effect of mistletoe on cancer cell growth has been reported, the underlying mechanisms to explain its anti-proliferative activity are not fully studied. Thus, we elucidated the potential molecular mechanism of the branch from taxillus yadoriki (TY) parasitic to Neolitsea sericea (NS) (TY-NS-B) for the anti-proliferative effect. Methods and Results : In comparison of anti-proliferative effect of TY from the host trees such as Cryptomeria japonica (CJ), Neolitsea sericea (NS), Prunus serrulata (PS), Cinnamomum camphora (CC) and Quercus acutissima (QA), TY-NS showed higher anti-cell proliferative effect than TY-CJ, TY-PS, TY-CC or TY-QA. In addition, the anti-proliferative effect of branch from TY from all host trees was better than leaves. Thus, we selected the branch from Taxillus yadoriki parasitic to Neolitsea sericea (TY-NS-B) for the further study. TY-NS-B inhibited the cell proliferation in the various cancer cells and downregulated cyclin D1 protein level. MG132 treatment attenuated cyclin D1 downregulation of cyclin D1 protein level by TY-NS-B. In addition, TY-NS-B increased threonine-286 (T286) phosphorylation of cyclin D1, and the mutation of T286 to alanine (T286A) blocked cyclin D1 proteasomal degradation by TY-NS-B. But the upstream factors related to cyclin D1 degradation such as ERK1/2, p38, JNK, GSK3β, PI3K, IκK or ROS did not affect cyclin D1 degradation by TY-NS-B. However, LMB treatment was observed to inhibit cyclin D1 degradation by TY-NS-B, and T286A blocked cyclin D1 degradation through suppressing cyclin D1 redistribution from nucleus to cytoplasm by TY-NS-B. In addition, TY-NS-B activated CRM1 expression. Conclusion : Our results suggest that TY-NS-B may suppress cell proliferation by downregulating cyclin D1 protein level through proteasomal degradation via T286 phosphorylation-dependent cyclin D1 nuclear export. These findings will provide the evidence that TY-NS-B has potential to be a candidate for the development of chemoprevention or therapeutic agents for human cancer.

Background : Vaccinium oldhamii is a Korean native tree, which is deciduous and shrub tree with broad leaf. It was used primarily for edible or medicinal purposes for bladder infection in Korea and China. In addition, it has been reported to be used for treating inflammation, gonorrhea, vomiting, diarrhea and eruption. In this study, we evaluated the anti-inflammatory effect of the branch of Vaccinium oldhamii and elucidated the potential mechanisms in LPS-stimulated RAW264.7 cells. Methods and Results : In the comparative experiment for the inhibitory effect of the plant parts from Vaccinium oldhamii such as fruits, leaves and branches on NO production, we observed that the branch extracts showed the highest inhibitory effect. Thus, the further study was performed using the branch of Vaccinium oldhamii (VOB). VOB did not affect iNOS expression but significantly IL-1β expression, which indicates that VOB may block NO production through the inhibition of IL-1β expression. In elucidation of the potential mechanisms for anti-inflammatory effect, VOB inhibited the degradation of IκB-α which results in the inhibition of p65 nuclear accumulation and NF-κB activation. In addition, VOB suppressed the activation of ERK1/2, p38 and JNK. Conclusion : These results indicate that VOB may exert anti-inflammatory activity through the inhibiting NF-κB and MAPK signaling. From these findings, VOB has potential to be a candidate for the development of chemoprevention or therapeutic agents for the inflammatory diseases.

Background : Hibiscus syriacus is a widely cultivated ornamental shrub, found throughout eastern and southern Asia. The root of H. syriacus has been used in Asian folk medicine as a fungicide, antipyretic, and anthelmintic in the treatment of dysentery, eczema, tinea, and scabies. In this study, we evaluated the anti-inflammatory effect of 70% ethanol extracts of root from Hibiscus syriacus (RHS-E70) and elucidated the potential mechanisms in LPS-stimulated RAW264.7 cells. Methods and Results : RHS-E70 dose-dependently suppressed nitric oxide (NO) production in LPS-stimulated RAW264.7 cells. In addition, RHS-E70 attenuated LPS-mediated overexpression of iNOS and IL-1β. In elucidation of the potential mechanisms for anti-inflammatory effect, RHS-E70 inhibited the phosphorylation and subsequent degradation of IκB-α, which results in the inhibition of p65 nuclear accumulation and NF-κB activation. In addition, RHS-E70 suppressed the activation of ERK1/2 and p38, which results in the inhibition of ATF2 phosphorylation and subsequent ATF2 nuclear accumulation. Conclusion : These results indicate that RHS-E70 may exert anti-inflammatory activity through the inhibiting NF-κB and MAPK signaling. From these findings, RHS-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for the inflammatory diseases.

Background : Ginseng (Panax ginseng) has been reported to exert an anti-inflammatory activity in a variety of inflammatory. However, inflammation-regulatory activity of wood-cultivated ginseng has not been thoroughly evaluated. In this study, we evaluated the anti-inflammatory effect of wood-cultivated ginseng and elucidated the potential mechanisms in LPS-stimulated RAW264.7 cells. Methods and Results : Inhibitory effects of the old wood-cultivated ginseng (WCG-O), young wood-cultivated ginseng (WCG-Y) and ginseng (G) on NO and PGE2 production were examined using the Griess assay and ELISA kit. Suppressive effects of WCG-O on inflammatory gene expression, transcriptional activation, and inflammation signaling events were investigated using Western blot analysis, RT-PCR analysis and luciferase activity reporter gene assay. WCG-O dose-dependently suppressed nitric oxide (NO) and Prostaglandin E2 (PGE2) production in LPS-stimulated RAW264.7 cells. In addition, WCG-O attenuated LPS-mediated overexpression of iNOS and COX-2. In addition, WCG-O blocked the expression of TNF-α and IL-1β in LPS-stimulated RAW264.7 cells. In elucidation of the potential mechanisms for anti-inflammatory effect, WCG-O inhibited the activation of IκK-α/β, the phosphorylation of IκB-α, and degradation of IκB-α, which results in the inhibition of p65 nuclear accumulation and NF-κB activation. In addition, WCG-O suppressed the activation of ERK1/2, p38 and JNK, which results in the inhibition of ATF2 nuclear accumulation. Conclusion : These results indicate that WCG-O may exert anti-inflammatory activity through the inhibiting NF-κB and MAPK signaling. From these findings, WCG-O has potential to be a candidate for the development of chemoprevention or therapeutic agents for the inflammatory diseases.

Background : Mistletoe has been used as the herbal medicine to treat hypertension, diabetes mellitus, inflammation, arthritis and viral infection. In this study, we evaluated the anti-inflammatory effect of extracts of branch from Taxillus yadoriki being parasitic in Neolitsea sericea (TY-NS-B) using in vitro model. Methods and Results : TY-NS-B significantly inhibited LPS-induced secretion of NO and PGE2 in RAW264.7 cells. TY-NS-B was also observed to inhibit LPS-mediated iNOS COX-2 expression. In addition, TY-NS-B attenuated production of inflammatory cytokines such as TNF-α and IL-1β induced by LPS. TY-NS-B blocked LPS-mediated inhibitor of IκB-α, and inhibited p65 translocation to the nucleus and NF-κB activation. Furthermore, TY-NS-B reduced the phosphorylation of MAPKs such as p38 and JNK, but not ERK1/2. In addition, TY-NS-B increased ATF3 expression and ATF3 knockdown by ATF3 siRNA attenuated TY-NS-B-mediated inhibition of pro-inflammatory mediator expression. Conclusion : Collectively, our results suggest that TY-NS-B exerts potential anti-inflammatory effects by suppressing NF-κB and MAPK signaling activation, and increasing ATF3 expression. These findings indicate that TY-NS-B could be further developed as an anti-inflammatory drug.

In this study, we evaluated anti-inflammatory effect of biji in LPS-stimulated RAW264.7 cells. Biji inhibited the generation of NO and PGE2 through the suppression of iNOS and COX-2 expression. In addition, biji attenuated the expression of TNF-α and IL-1β induced by LPS. Biji blocked LPS-mediated IκB-α degradation and subsequently inhibited p65 nucleus accumulation in RAW264.7 cells, which indicates that biji inhibits NF-κB signaling. In addition, biji suppressed p38 phosphorylation induced by LPS. Our results suggests that biji may exert anti-inflammatory activity through blocking the generation of the inflammatory mediators such as NO, PGE2, iNOS, COX-2, TNF-α and IL-1β via the inhibiting the activation of NF-κB and p38. From these findings, biji has potential to be a candidate for the development of chemoprevention or therapeutic agents for inflammatory diseases.

Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a GSK3β inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced GSK3β inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through GSK3β-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

Background : The young stem of Cinnamomum cassia (YSC) as traditional Chinese medicines has been reported to show a variety of pharmacological properties such as anti-allergy, insecticidal, antimicrobial, antiulcer, anti-inflammatory, immune-suppressive, and neuronal death prevention, tyrosinase inhibition and anticancer, antioxidant and free radical scavenging, as well as antidiabetic and aldose reductase inhibition activities. In this study, we elucidated apoptotic effect and potential molecular mechanism of hot water extracts from YSC (YSC-HW) against human colorectal cancer cells. Methods and Results : YSC-HW treatment increased ROS level and induced ROS-dependent DNA damage in human colorectal cancer cells. ROS generation mediated by YSC-HW induced DNA induced apoptosis and reduction of cell viability in human colorectal cancer cells. YSC-HW ROS-dependently induced NF-kB activation through p65 nuclear translocation via IkB-α degradation, which exerted the induction of apoptosis. In addition, YSC-HW activated ATF3 expression dependent on ROS, which resulted in apoptosis. Conclusion : Our results suggest that YSC-HW may induce apoptosis through ROS-activation of NF-kB and ATF3 in human colorectal cancer cells. From these findings, YSC-HW has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

In this study, we produced the recombinant lunasin peptide using E. coli and P. pastoris, and evaluated biological activity of the recombinant lunasin peptide. Lunasin peptide was produced from E. coli transfected with pPGEX-lunasin expression vector and P. pastoris GS115 transfected with pPIC-lunasin expression vector. These recombinant lunasin peptides were similar to the synthetic lunasin peptide in the identification by LC-ESI-MS. In addition, the recombinant lunasin peptide from E. coli and P. pastoris was bound in the chromatin, and inhibited histone acetylation and the activity of histone acetyltransferase. These findings suggest that the production of the lunasin peptide using E. coli and P. pastoris will be useful for industrial utilization of lunasin peptide.