• The Journal of Korean Physical Therapy
• /
• 제19권1호
• /
• pp.57-66
• /
• 2007

Purpose: We investigated the effects of the combined therapy in rats with rheumatoid arthritis induced by type II collagen for 28 days, which consisted of the oral administration of the AR and EA applied to zusanli acupoint(ST36). Methods: Normal group was oral administered with 0.9% NaCl $0.5\;m{\ell}/day$ to normal rats. Control group was oral administered with 0.9% NaCl $0.5\;m{\ell}/day$ to arthritic rats. Group I was oral administered with AR 500 mg/kg $0.5\;m{\ell}/day$ to arthritic rats. Group II was given 2 Hz EA of ST36 in the test group for 30 min/day to arthritic rats. Group III was oral administered with AR 500 mg/kg $0.5\;m{\ell}/day$ and 2 Hz EA of ST36 in the test group for 30 min/day to arthritic rats. We Observed effect of the histopathological changes by H&E stain of liver, kidney, knee joint and ELSIA of cytokines($TNF-{\alpha}$). Results: 1. The vacuolization of liver tissue was decreased in group I, II, III comparing with control group. 2. The glomerular sclerosis of kidney tissue was decreased in group I, II, III comparing with control group. 3. The erosion of arthritic site of knee joint tissue was decreased group I, II, III comparing with control group. In particular group III was the most effective comparing with group I, II on the histopathological view. 4. In the ELSIA test of $TNF-{\alpha}$ concentration, Control group significantly increased in the concentration more than group I, II, III. The rate of increase in concentration slowed down in group III more than group I, II(p<0.05). Conclusion: It is concluded that 500 mg/kg of AR extracts and EA have clear therapeutic effect on the rheumatoid arthritis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제14권4호
• /
• pp.199-204
• /
• 2010

The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.

• 한국약용작물학회:학술대회논문집
• /
• 한국약용작물학회 2007년도 춘계학술발표회
• /
• pp.261-262
• /
• 2007

• 한국약용작물학회:학술대회논문집
• /
• 한국약용작물학회 2007년도 추계학술발표회
• /
• pp.314.1-314.1
• /
• 2007

• 동의생리병리학회지
• /
• 제23권5호
• /
• pp.1106-1115
• /
• 2009

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th1 7 cells. DBA/1OlaHsd mice were immunized with bovine type II collagen (CII). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-$\alpha$, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-$\alpha$, IL-6, IL-17 and collagen II-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 mg/kg or 200 mg/kg) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 mg/kg) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

• Journal of Acupuncture Research
• /
• 제28권1호
• /
• pp.37-44
• /
• 2011

배경 및 목적 : 봉독약침요법(bee venom pharmacopuncture, BVP)은 rheumatoid arthritis(RA)의 치료에 활용되고 있으나, RA로 인한 염증성 통증에 대한 봉독약침의 진통효과와 specific mechanism은 아직까지 명확하게 밝혀지지 않았다. 이에 본 연구에서는 RA animal model로서 collagen-induced arthritis(CIA) rat model에서 봉독약침의 a1-adrenergic, 5HT-3 그리고 muscarinic cholinergic mechanism을 확인하고자 한다. 방법 : CIA를 유도하기 위하여 male Sprague-Dawley rat에 freund's incomplete adjuvant에 유화(乳化)시킨 bovine type II collagen을 주입하고 14일 후 booster injection 시행하였다. 진통효과는 tail flick latency (TFL)로 평가하였다. 결과 : 관절염의 유도 이후 염증성 통증 역치는 시간이 지나면서 낮아지며, 5주 이후로는 통증 역치에 큰 변화가 없이 유지되었다. 첫 번째 immunization으로부터 5주 경과 후 족삼리($ST_{36}$)에 봉독약침처치(0.25 mg/ kg)를 시행하여 유의한 진통효과를 관찰하였다. 또한 봉독약침의 진통효과는 ondansetron(5HT-3 receptor antagonist, 0.5mg/kg, i.p.), atropine(muscarinic cholinergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의하여 억제되었으나, prazosin(a1-adrenergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의해서는 억제되지 않았다. 결론 : 봉독약침은 CIA로 인한 염증성 통증에 유의한 진통효과를 나타내며 그 analgesic mechanism은 5HT-3와 muscarinic cholinergic receptor에 의하여 매개되며 a1-adrenergic receptor에 의하여 매개되지는 않았다.

• Biomolecules & Therapeutics
• /
• 제23권2호
• /
• pp.195-200
• /
• 2015

We tested the hypothesis that micro-computed tomography (micro-CT) analysis provides a better quantitative readout of the therapeutic potential of methotrexate (MTX) for treating collagen-induced arthritis (CIA) in rats and compared to conventional histopathological examination. Rats were divided into three groups: Group 1 (G1) was treated with 0.9% saline, whereas groups 2 (G2) and 3 (G3) were boosted with type II collagen at days 0 and 7. Following the first collagen immunization, rats in G1 and G2 were treated with 0.9% saline and those in G3 were treated with 1.5 mg/kg MTX from day 14 to 28. All rats were sacrificed on day 28, at which point and all hind knee joints were analyzed by micro-CT and histopathological examination. Micro-CT analyses showed that bone volume and trabecular number were significantly decreased in G2 and G3 compared to G1 (p<0.01), as was percent bone volume (p<0.05 and p<0.01, respectively). However, bone surface/bone volume was significantly increased in G2 and G3 compared to G1 (p<0.05 and p<0.01, respectively). Trabecular separation was significantly increased in G3 compared to G1 (p<0.05). Histopathological examination showed that knee joints of rats in G2 and G3 showed severe joint destruction with inflammatory cell infiltration. However, cartilage destruction was slightly reduced in G3 compared to G2. Taken together, these results suggest that MTX treatment reduced cartilage destruction in rats with CIA, and micro-CT analyses made it possible to quantify arthritic bony lesion.

• 대한한의학회지
• /
• 제23권4호
• /
• pp.98-104
• /
• 2002

Objectives: Calpain, a calcium-dependent cysteine proteinase, may be one of the proteolytic enzymes that mediate cartilage degradation associated with rheumatoid arthritis. The object of this study is to ascertain immunohistochemically whether calpain is present in the inflamed joints of collagen-induced arthritis of rats, and examine the effect of Cortex Acanthopanacis Senticosi on the expression of calpain. Methods: Male Lewis rats, around 200g of body weight, were immunized with bovine type II collagen. After 3 weeks from first immunization, rats were divided into arthritic control (n=6) group and Cortex Acanthopanacis Senticosi-treated (n=6) group. Non-immunized rats served as the normal (n=6) group. All animals were sacrificed at 15 days post-treatment and tibiotarsal joints were removed. Calpain immunohistochemistry was performed on the midsagittal section of the tibiotarsal joint. Results: All animals of the control and treated groups showed ankylosing osteoarthritis. However, the animals of the treated group showed alleviation in the fibrous ankylosis, destruction of articular cartilage and destruction of subchondral bony tissue compared with the animals of the control group. Calpain was expressed in the chondrocyte lacunae of growing articular cartilage, in the skeletal muscle fibers, in the peripheral nerves, and in the vessel walls around the joints of all groups. In the control and treated groups, calpain was also expressed in proliferating synovial epithelia, subsynovial stroma cells, surface of articular cartilage, and fibrous pannus around destructive subchondral bony tissue. However, the expression density of calpain in the treated group was diminished compared with the control group, especially in surface of articular cartilage and fibrous pannus. Conclusions: These observations indicated that calpain plays an important role in the destruction of cartilage and bone in collagen-induced arthritis of rats, and also indicated that Cortex Acanthopanacis Senticosi inhibits the development of arthritis by decreasing the expression of calpain.

• Journal of Acupuncture Research
• /
• 제22권2호
• /
• pp.43-53
• /
• 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 Microbiology and Biotechnology
• /
• 제31권10호
• /
• pp.1401-1408
• /
• 2021

This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In micro-computed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1β and IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1β induction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.