• Journal of Acupuncture Research
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• 제22권2호
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• pp.43-53
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• 2005

Objective: Since Ulmus davidiana Planch (Ulmaceae) has been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions, this study was undertaken to address whether the water extract of the bark of Ulmus davidiana Planch (Ulmaceae) (UD) could modulate the expression of inducible inflammatory cytokines in mice. The present study was also done in order to assess the therapeutic effects of UD in collagen-induced arthritis (CIA) in mice. Methods : DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with UD orally at 100 mg/kg once a day for 3 weeks. Paws were evaluated macroscopically for redness, swelling and deformities. The levels of $TNF-{\alpha}\;and\;IL-1{\beta}$ in the ankle were examined. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of UD significantly suppressed the progression of CIA and inhibited the production of $TNF-{\alpha}\;and\;IL-1{\beta}$ in the paws. The erosion of cartilage was dramatically reduced in mouse knees after treatment with UD. In the serum of UD-treated mice, the levels of IL-4 and IL-10, anti-inflammatory cytokines, were increased. Conclusion : From the results, it was concluded that administration of UD has therapeutic effects on CIA including protection of cartilage and RA for a potential therapy.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.83-92
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• 2005

Objective: Although the effect of Ulmus davidiana Planch (UD) extracts on collagen-induced-arthritis (CIA) and bone metabolism has been studies, research on its effect on human immunomodulatory activity is further a due. The objective of the present study was to investigate the immunomodulatory activity of UD on cellular and humoral immunity. Methods : Oral administration of the ethanolic and water extracts of UD, at doses of 20, 100 and 200 mg/kg in mice, dose dependently potentiated the delayed type hypersensitivity reaction induced both by sheep red blood cells (SRBC) and oxazolone. Results : It significantly enhanced the production of circulating antibody titre in response to SRBC in mice. Extracts of UD failed to show any effect on macrophage phagocytosis. Chronic administration of UD extracts significantly ameliorated the total white blood cell count and also restored the myelosuppressive effects induced by cyclophosphamide. Conclusion : The present investigation reveals that UD extracts possesses immunomodulatory activity.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.55-70
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• 2005

Objective: Ulmus davidiana Planch (Ulmaceae) has long been known to have anti-inflammnatory in the traditional Korean medicine. UD has been reported as a good enhancer for bone healing. Methods : In this experiment, we investigate the Inhibitory effects of UD on bone resorption using the bone cells culture. Different concentrations of crude extract of UD were added to mouse bone cells culture. The mitochondria activity of the bone cells after exposure was determined by colorimetric MIT assay. It was demonstrated that UD has potential effects on bone cells culture without any cytotoxicity. The most effective concentration of UD on bone cells were $100\;{\mu}g/ml$. Cathepsin K (Cat K) is the major cysteine protease expressed in osteoclasts and is thought to play a key role in matrix degradation during bone resorption. Results : When mouse long bone cells including osteoclasts and osteoblast were treated with the PI3-Kinase inhibitor, wortmannin (WT), WT prevented the osteoclast-mediated intracellular processing of Cat K. Similarly, treatment of osteoclasts-containing long bone cells with UD extracts prevented the intracellular maturation of Cat K, suggesting that UD may disrupt the intracellular trafficking of pro Cat K. This is similar to that of WT. Since secreted proenzymes have the potential to reenter the cell via mannose-6-phosphate (M6P) receptor, to prevent this possibility, we tested WT and UD in the absence or presence of M6P. Inhibition of Cat K processing by WT or UD was observed in a dose-dependent manner. Furthermore, the addition of M6P resulted in enhanced potency of WT and UD. Conclusion : UD dose-dependently inhibited in vitro bone resorption with a potency similar to that observed for inhibition of Cat K processing.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.33-41
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• 2005

Objective : The effect of Ulmus davidiana Planch(UD), which has long been known to have anti-inflammation and protective effects on damaged tissue, inflammation and bone among other functions, on the development of type II collagen (CII)-induced arthritis (CIA) in rats was studied. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA)or saline during the experiment. When compared with rats treated with saline as control, UDHA at doses of more than $20{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2, interleukin-6, $IFN-{\gamma}$ when the cells were obtained from rats 14 days after immunization and cultured in vitro with CII. Results : When rats were injected intraperitoneally, UD -treated group and control group rats did not differ significantly when low doses of UD was given to rats. Conclusion : The recommended dose of UD in the management and treatment of rat CIA will be more than $20{\mu}g/100\;g$, which is two-firth of human therapeutic dose. From the results, it was concluded that the effect of UDHA is dependent of dosage.

• 한방안이비인후피부과학회지
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• 제24권1호
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• pp.86-95
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• 2011

Objectives : Ulmus davidiana (UD) has been widely used in Korean herbal medicines used for treatment of acute and chronic inflammatory diseases, such as rhinitis, asthma, and abscess. In this study, To investigated the protective effect of UD on type 1 allergic response, we determined whether UD inhibits early and late allergic response. Methods : The effect of UD was analyzed by ELISA and RT-PCR in RBL-2H3 cells. Levels of ${\beta}$ -hexosaminidase, interleukin (IL)-4 and TNF-${\alpha}$ were measured using enzyme-linked immunosorbent assays (ELISAs). mRNA levels of COX-2 and T-helper type 2(Th2) cytokines were analyzed with RT-PCR. Results : We found that UD suppressed ${\beta}$-hexosaminidase release in RBL-2H3 not only by the PMA plus A23187 stimulation, but also by the IgE-DNP-HSA stimulation at the antigen-antibody binding stage and antibody-receptor binding stage. UD also significantly inhibited COX2 level, along with reduced Th2 cytokine levels, such as IL-3, IL-4, IL-5, IL-13, GM-CSF, and TNF-${\alpha}$ in RBL-2H3. Conclusions : Our results indicate that UD protects against type 1 allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and expression of COX2 and Th2 cytokines.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.91-102
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• 2006

Objectives : Ulmus davidiana Planch (UD) has long been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions. Methods : This study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoclasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2) and is highly expressed in osteoclasts. Mouse osteoclasts were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with UD extract. Results : Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) by Cell viability assay, Cell cycle analysis, Immunohistochemical analysis of PCNA expression, Western blot analysis and PGE2 Enzyme immunoassay (EIA). UD demonstrated a strong growth inhibitory action in both tested osteoclasts cells. The IC50s were $10\;{\mu}g/ml$ for UD, $6\;{\mu}M$ for celecoxib and $42\;{\mu}M$ for indomethacin. UD, as well as celecoxib and indomethacin, suppressed proliferation cell nuclear antigen expression and PGE2 synthesis in osteoclasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. Conclusion : UD selectively and effectively inhibits osteoclasts cell growth in vitro. Inhibitory action of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

• Journal of Nutrition and Health
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• 제39권8호
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• pp.721-727
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• 2006

This study was conducted to investigate the effects of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts on blood hemoglobin, $HbA_{1c}$, levels and biomarkers in the streptozotocin (STZ)-induced diabetic rats. Male Wistar rats divided into normal and diabetic groups. The diabetic groups subdivided into the control group (DM) and Araliaceae water extracts supplemented groups: Aralia elata (AE), Acanthopanacis cortex (AC) and Ulmus davidiana (UD). The extracts were supplemented in diet base on 11.42 g of raw Araliaceae/kg diet for 7 weeks. The diabetes was induced by injecting 572 (55 mg/kg B.W., i.p.) once 2 weeks before sacrifying. Relative weights of liver were significantly lowered in the DM group compared to the normal group, whereas those of kidney and heart were significantly increased in the DM group. Supplementation of the Araliaceae water extracts improved reduced liver weights in STZ-induced diabetic rats. Blood glucose level was significantly higher in the DM group than in the normal group, whereas insulin contents were significantly lowered in the DM groups. However, these parameters were normalized in the An, AC and UD supplemented groups, respectively. Blood hemoglobin and $HbA_{1c}$ levels were significantly higher in the DM group than in the normal group. When all of Araliaceae water extracts were supplemented to the diabetic rats lowered hemoglobin and $HbA_{1c}$ levels. Red blood cell, white blood cell and Lymphocyte were significantly higher in the DM group than in the normal group. The supplementation of Araliaceae family water extracts significantly lowered these parameters compared to the DM group. MCV, MCH contents were declined in the DM group, while the supplementation of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts elevated of these contents in STZ-induced diabetic rats. Accordingly, these results indicate that Aralia elata, Aeanthopanacis corex and Ulmus davidiana water extracts would seem to improve the blood biomarkers in STZ-induced diabetic rats.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제15권6호
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• pp.339-344
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• 2011

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD ($10{\sim}100{\mu}g/ml)$ did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of $0.1{\sim}10{\mu}g/ml$ with an $ED_{50}$ value of $2{\mu}g/ml$. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high $K^+$ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.

• 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.