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 : 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.
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 production method of ginseng seedlings for ginseng cultivation is very important to ensure healthy rooting system as well as high quality, and yield of the resultant plants. This study was carried out to compare the growth characteristics of 2- year-old ginseng plants that were produced from seedlings grown in self soil nursery (SSN), nursery soil (NS) or hydroponic culture (HC). Methods and Results: The shading prop used was composed of four-layered 4 polyethylene (blue 3 + black 1) shade screen. The management of main field was done by inserting oil cake (1,200 ㎏/10 a) and then allowing Sudan grass to grow for a year. Seedling transplantation was carried out on April 6. Root growth was measured on October 25. Root weight was observed to be excellent at 6.0 g, following SSN transplantation. Root length was 21.2 ㎝ for HC seedlings, but these plants had a physiological disorder (i.e., rusty root), in 83.5% plants of this treatment. The ratio of PD/PT (protopanaxadiol saponins / protopanaxatriol saponins) was higher in NS seedlings. Plant analysis revealed that Fe content was lower in HC seedlings with high rustiness. The growth of 2-years-old ginseng was different following these varying seedling cultivation methods, but seedlings from NS were not different from those grown in SSN. Conclusions: For the propagation of 2-year-old ginseng plants, NS seedlings may be a good substitute for SSN seedlings.
Background : The cultivation of wild greens in a forest farming system is an attractive alternative to wild harvesting, due to its much lower production cost compared with conventional cultivation, and its provision of a second income to the landowner. Yet little is known about the conditions that would maximize the growth and antioxidant activities of wild greens in a forest farming system. Thus, this study was conducted to evaluate the optimal conditions that would maximize antioxidant activities of Ligularia fischeri (Ledeb.) Turcz., being cultivated in three different cultivation systems in Korea. Methods and Results : After the fibrous roots of L. fischeri were planted in three different cultivation systems, this study was conducted to assess the effect on health-related properties such as total phenolic contents, flavonoids, DPPH (1,1-diphenyl-2-picrylhydrasyl) free radical scavenging activities and reducing power. From these harvests in different sites, extracts were prepared using methanol. Total phenolic content in forest farming system (1.061 ㎎·GAE/㎖) was higher than that in other products harvested in conventional and greenhouse system (0.666㎎·GAE/㎖). Also, flavonoid content was higher in forest farming system (0.124 ㎎·QE/ ㎖), compared to conventional and greenhouse system (0.084 ㎎·QE/㎖). Conclusions : Antioxidant activity and cultivation system seem to correlate with total polyphenol and flavonoid contents.