• 대한한방부인과학회지
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• 제23권1호
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• pp.1-11
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• 2010

Purpose: This study was designed to investigate the antimetastatic and immunomodulating effects of extracts of Ulmus davidiana extracts(U. D. Ex.). Methods: Antimetastatic experiments were conducted in vitro and in vivo by using colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell and Hela cell. To observe the immunomodulating effects of U. D. Ex., we measured IL-6, IL-10, IL-12 and TNF-$\alpha$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of U. D. Ex. significantly inhibited tumor metastasis in vivo. In vitro cytotoxicity analysis, cell growth are closer to 100% in case of Colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell and Hela cell at low concentration. In case of macrophage, cell proliferation is closer to 100% less than $250{\mu}g/ml$ of U. D. Ex.. The level of cytokine such as IL-6, IL-10, IL-12 which stimulates U. D. Ex. was increased in dose-dependent manner compared to the control group. In case of TNF-$\alpha$, the level was increased at concentration of $1,000{\mu}g/ml$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of U. D. Ex. on tumor metastasis. Conclusion: Ulmus davidiana appears to have considerable activity on the anti-metastasis by activation the immune system.

• 대한한의학방제학회지
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• 제16권2호
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• pp.229-241
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• 2008

Objectives : The purpose of this study is to investigate the effect of Ulmi Cortex(UC) on the cisplatin-induced cell death. Materials and Methods : I examined several kinds of cell populations such as $CD4^+$ T cells, $CD8^+$ T cells, macrophages and dendritic cells in spleen. Result : When cisplatin was injected to mice, UC recovered total number of cells in spleen and also the number of T cells, macrophages and dendritic cells. UC also effected the activation of $CD4^+$ and $CD8^+$ T cells such as $CD25^+$, $CD69^+$ cells. To further investigate the effect of UC on the cisplatin-induced cell death, I examined the death of splenocyte and total T cells. UC inhibited cisplatin-induced cell death. Conclusion : Taken together, my results suggest that UC may be a beneficial oriental medicine for side effects during anti-tumor therapy.

• 대한한방부인과학회지
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• 제20권3호
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• pp.35-44
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• 2007

Purpose: This study was conducted to investigate the anti-proliferative effects of Ulmi Pumilae Cortex Extracts(UPCE) on MCF-7(human, breast, adenocaecinoma) and NIH3T3 (human, murine, fibroblast). Methods: MCF-7 cells and NIH3T3 cells were cultured and seeded in cell culture plates, respectively. UPC was extracted with hot water and then further fractionated it into five types: hexane, chloroform, ethyl acetate, butanol, and water soluable fractions. These five different fractions from UPCE were tested for their anti-proliferative effects on MCF-7 cells and NIH3T3 cells by MMT assay. Results: Among the five solvent-fractions of UPCE, n-hexane fraction and ethyl acetate fraction showed a strong anti-proliferative effects on MCF-7 cells but they displayed significant cytotoxicity on NIH3T3 cells, too. On the other hand, chloroform fraction showed a marked anti-proliferative effects on MCF-7 cells and low cytotoxicity on NIH3T3 cells. Conclusion: Chloloform fraction from UPCE showed selective anti-cancer activities on human breast cancer cell MCF-7 relatively to the other fractions.

• 대한본초학회지
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• 제37권4호
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• pp.39-48
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• 2022

Objectives : In the present study, we assessed the effects of water extract of Ulmus davidiana(UED) on the learning and memory impairments induced by scopolamine in mice through its favorable acetylcholinesterase (AChE) activity and antioxidant effect. Methods : The memory and cognitive enhancing effect of the UDE was investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. In addition, to examine the mechanism of UDE using acetylcholinesterase (AChE) and antioxidant activity. Results : The water extract of UDE (100, and 200 mg/kg) significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P < 0.05). Moreover, UDE (100, and 200 mg/kg) also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P < 0.05). On the Y-maze test, UDE (100, and 200 mg/kg) also significantly reversed scopolamine-induced cognitive impairments in mice (P < 0.05). In an in vitro study, UDE was found to inhibit acetylcholinesterase, changes in neurotrophic factor (CREB), and antioxidant activity in a dose-dependent manner. Conclusions : The water extract of UDE dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent on the learning models. These results suggest that the administration of UDE enhances learning and memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.13-22
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• 2005

손상된 조직의 보호와 항염증작용이 있는 것으로 알려진 유근피를 수액추출하여 골다공증의 치료에 응용 가능한가를 실험하였다. 이전의 실험에서 유근피 추출액이 파골세포를 함유한 장골세포의 치료를 통해 Cathepsin K를 억제하는 것을 확인 하였었다. 이를 통하여 유근피는 골다공증 치료에서 골재흡수억제제로 서의 prodrug의 역할을 할 수 있음을 시사하였다. 본 실험에서는 MC3T3-El pre-osteoblastic 세포조직을 이용하여 골화를 유발한 상태에서 유근피가 골아세포의 성장과 감작에 대한 것을 in vitro로 연구하였다. 이 결과 유근피는 용량과 시간의존적으로 ALP의 활동을 향상시킴으로써 강화작용이 있음을확인할 수 있었다. 투여량은 최소치 $50{\mu}g/m{\ell}$에서 최대치 $150{\mu}g/m{\ell}$에서 관찰되었다. $100{\mu}g/m{\ell}$ UD에서 bone morphogenetic protein-2의 향상을 관찰할 수 있었으며, MC3T3-El 세포내의 ALP mRNA농도역시 증가 하였다. $60{\mu}g/m{\ell}$ UD에서 Type I collagen mRNA에 대해서 오랜 배양 기간 동안 약간의 증가를 나타내었으나 15-20일 사이의 배양에서는 급격히 유전자 발현을 억제하는 것으로 나타났다. 이러한 결과는 골아 세포의 감작을 통해 유근피가 골대사에 영향을 미침을 시사하는 것이다. 그러므로 추후 연구를 통하여 일반적인 골대사질환에 유근피를 적극적으로 활용할 수 있음을 알 수 있었다.

• 동의생리병리학회지
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• 제21권1호
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• 대한한방내과학회지
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• 제21권2호
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• pp.259-266
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• 2000

Objectives : The effects of aqueous extracts of Cortex ulmi pumilae (a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origm hepatoma cell lines, HepG2. Methods : The death of HepG2 cells was markedly induced by the addition of extracts of Cortex ulmi pumilae in a dose-dependent manner. The apoptotic characteristic ladder pattern of DNA strand break was not observed in cell death of HepG2. In addition, it was not shown nucleus chromatin condensation and fragmentation under hoechst staining. However, by the using annexin V staining assay, externalizations of phosphatidylserine in HepG2 cell which were treated with Cortex ulmi pumilae extracts were detected in the early time (at 9 hr after extract treatment). Furthermore, LDH release was not detected in this early stage. Therefore, Cortex ulmi pumilae extracts-induced cell death of HepG2 cells is mediated by apoptotic death signal processes. Result : The activity of caspase 3-like proteases remained in a basal level in HepG2 cells which treated with the extract of Cordyceps sinensis. However, it was markedly increased in HepG2 cells which treated with two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) which were differently extracted (respectively, 2.3 and 3.3 fold). On a while, the phosphotransferase activities of JNK1 was markedly induced in HepG2 cells which were treated with two extracts of Cortex ulmi pumilae. On the contrary, the activation of transcriptional activator, activating protein1(AP-1) and NF-kB were severely decreased by these two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K). In addition, antioxidants (GSH and NAC) and intracellular $Ca2^+$ level regulator (Bapta/AM and Thapsigargin) did not affect Cortex ulmi pumilae extracts-induced apoptotic death of HepG2 cells. Conclusions : In conclusion, our results suggest that two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) induces the apoptotic death of human liver origin hepatoma HepG2 cells via activation of caspase 3-like proteases as well as JNK1, and inhibition of transcriptional activators, AP-1 and $NK-{\kappa}B$.

• 대한한방내과학회지
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• 제38권6호
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• pp.863-876
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• 2017

Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.

• Journal of Applied Biological Chemistry
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• 제61권2호
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• pp.119-124
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• 2018

두충(Eucommia ulmoides Oliver)잎 아세톤 추출물의 in vitro 항암 및 항산화 활성을 조사하였다. 두충잎 아세톤 추출물의 수율은 $1.13{\pm}0.033%$ (w/w)이었고, 총 페놀성 화합물 함량은 $36.7{\pm}1.96mg$ gallic acid equivalents/g-추출물로 나타났다. 세포증식을 절반 억제하는 추출물의 농도인 $GI_{50}$값은 사람의 암세포인 비소세포폐암세포(A549)에서 $53.4{\mu}g/mL$, 결장암세포(SNU-C4)에서 $53.8{\mu}g/mL$ 및 자궁경부암세포(HeLa)에서 $88.3{\mu}g/mL$이었고, 사람의 정상세포인 배아 폐 상피세포(L132)에서는 $153.9{\mu}g/mL$로 나타났다. 두충잎 아세톤 추출물은 사람의 정상세포에는 낮은 독성을 나타내면서 농도에 비례하여 사람의 비소세포폐암세포(A549)와 결장암세포(SNU-C4)의 증식을 효과적으로 억제하였다. DPPH 유리라디칼을 절반 소거하는 추출물의 농도인 $EC_{50}$값은 2 mg/mL 정도로 높게 나타났고, 환원력의 $EC_{50}$값은 $275.8{\mu}g/mL$, 지질과산화를 절반 저해하는 농도인 $EC_{50}$값은 $257.9{\mu}g/mL$이었다. 유근피 아세톤 추출물은 농도에 비례하여 우수한 환원력 및 지질과산화 억제활성을 보여주었다.

• Journal of Acupuncture Research
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• 제24권6호
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• pp.15-27
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• 2007

Objectives : The purpose of this study is to investigate the effectiveness of Ulmus davidiana Planch herbal acupuncture(UA) to inhibit nuclear $factor(NF)-{\kappa}B$ activation on type II collagen-induced arthritis (CIA) in mice. Methods : Using an in vitro test, the synoviocytes picked out from the experimental CIA mice were subcultured. The synoviocyte cells were treated with phorbol-12-myristate-13-acetate(PMA) for 1 hour prior to the addition of indicated concentrations($0.4\;-\;1.0mg/m{\ell}$) of UA, and the cells were further incubated for 24 hours. The in vivo test, $NF-{\kappa}B$ p65, inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), vascular cell adhesion molecule(VCAM)-1 production and apoptosis was observed by immunohistochemical staining. Results : The PMA-induced $I{\kappa}B$ kinase(IKK), iNOS and COX-2 mRNA expression were dose-dependently decreased in UA treated synoviocytes. Using the in vivo test, the number of eosinophils in mice treated with UA noticeably decreased in the the CIA group(P<0.05 using student t test). In mice treated with UA, there was less cartilage erosion. less bone destruction, mild synovial hyperplasia, mild fibrosis, and mild angiogenesis with less MIP-2 production. By immunohistochemical staining, suppression of $NF-{\kappa}B$ p65, iNOS production, inhibition of COX-2 production, inhibition of VCAM-1 production and inducing apoptosis were observed. Conclusions : These results suggest that UA might be applicable to the therapy of RA to suppress $NF-{\kappa}B$ activation.