• 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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• 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.

• 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.

• 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.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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• 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 Acupuncture Research
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• 제25권2호
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• pp.119-127
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• 2008

목적 : 골관절염치료에 빈용되는 유근피 약침액의 처치가 생쥐의 파골세포에 있어서 골재흡수의 저해에 미치는 영향을 알아보고자 하였다 방법 : 생쥐에게 유근피 약침액을 두개골 세포에 전, 후 처치하여 골재흡수에 대한 유근피 약침액의 억제 활성능을 검토하였다. 결론 : 염증성 cytokine 중 $IL-1{\beta}$ 유도인자인 PGE와 LPS처리로 $IL-1{\beta}$생성이 증가되었으나, 유근피 약침액 처치군은 이를 억제하였다. 유근피 약침액 전처리군에서도 $IL-1{\beta}$ 생성이 억제되었다. 유근피 약침액 처치군은 PGE2유발 $IL-1{\beta}$ 전사를 억제하였으며, PGE2 유발 $IL-1{\beta}$ 유도는 cAMP antagonist인 Rp-cAMP와 protein kinase A(PKA)저해제에 의해서도 억제되어 $IL-1{\beta}$ 발현에 cAMP, PKA 신호전달경로가 관여함을 시사하였다. 본 연구에서 유근피 약침액은 강한 항 관절염효과와 골재흡수 저해 활성이 있으며, 관절염 치료, 예방에 유의함을 밝힌 것으로 사료된다.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.1-12
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• 2005

유근피의 ethanol 추출 약침액 (EE-UD)과 수욕 약침액 (WE-UD)은 cathepsin K 와 L의 우수한 억제물로 밝혀졌다. WE-UD는 IC50 수치가 5.32 ${\square}g$/ml일때 cathepsin K를 억제하였고 6.34 ${\square}g$/ml일때 cathepsin L을 억제하였다. 그러나 EE-UD는 cathepsin K와 L을 1.45 ${\square}g$/ml와 2.43 ${\square}g$/ml 수준에서 억제 활동을 보여 WE-UD보다 많은 유의성을 보였다. EE-VD는 0.8 ${\square}g$/ml의 Ki 수치로 cathepsin K에 대하여 우수한 억제물임을 관찰할 수 있었다. 이러한 활동은 분석실험에서도 pH 7.0의 glutathione와 같이 작용하였을때 10배로 늘어났다. 또한 이는 GSH thiolate 음이온의 조합을 지원하므로서 이러한 유효성의 증가는 아마도 효소의 활동 장소로 향한 약침액 배합들의 향상된 화학 작용으로 인한 것으로 사료되었다. WE-UD는 시간 의존적 억제 성을 보임으로서 실험과정 중에 불변의 cathepsin K의 분열과 합성 속도를 알 수 있게 해주었다. 마지막으로 EE-UD는 실험용 쥐의 파골세포와 설치류의 골이 관련된 실험에서 골 재흡수성을 억제함이 입증되었다. WE-UD는 cathepsin K 와 L, 그리고 골의 collagen에서의 단백질 분해를 억제하는 작용이 있음을 증명하였다. 이와 같은 결과들은 cathepsin K로 인하여 유발된 골 손상의 진행을 예방해주는데 효과적인 것임을 강력히 시사하였으며 또한 골수세포들의 골 재흡수 활동에 효과적인 것이라는 결론을 얻었다.