• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.212-224
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• 2013

This study intends to clarify how Sayeok-tang(here in after reffered to SYT) affect C57BL/10 mice whose osteoarthritis was induced by papain. Osteoarthritis was induced by injecting papain in the knee joint of 3 groups(n=6) of mice. Normal group was non-treatment group and was not injected papain, whereas control mice were orally administered with $200{\mu}{\ell}$ of physiological saline. Positive comparison group was medicated with 100 mg/kg of Joins$^{(R)}$ mixed with $200{\mu}{\ell}$ of physiological saline. Experimental group was medicated with 400 mg/kg of SYT mixed with $200{\mu}{\ell}$ of physiological saline. Both Positive and experimental comparison groups were orally medicated once per day for 4 weeks. After the experiment, the functions of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological changes in the knee joint structures were observed. As results, SYT had no significant effect on the liver and kidney functions. Interleukin-$1{\beta}$(IL-$1{\beta}$), interleukin-6(IL-6), monocyte chemo attractant protein-1(MCP-1) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were significantly decreased. Inflammation cytokines in joints were all significantly decreased. Prostaglandin $E_2(PGE_2)$, thromboxane $B_2(TXB_2)$ were significantly decreased. Destruction of cartilage on micro computed tomography(CT)-arthrography was meaningfully decreased. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small. Based on all results mentioned above, Sayeok-tang(SYT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• The Journal of Korean Medicine
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• v.34 no.1
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.1
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• pp.25-49
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• 2013

Objectives : This study was carried out to know the anti-osteroarthritic effects of Bangkibokryeong-tang(Fanjifuling-tang(BBT)) on the papain-induced osteoarthritis C57BL/10 mouse. Methods : Osteoarthritis was induced by injection of papain(6 ${\mu}l$) into knee joint of mouse. Osteoarthritic mice were divided into 4 groups(normal, control, joins(R), BBT). The injection did not fit the normal group. A week later, after the injection of papain, control group was taken normal saline 200 ${\mu}l$, positive control group was taken joins(R)(100 mg/kg), treated group was taken extract of Bangkibokryeong-tang(Fanjifuling-tang(BBT))(400 mg/kg). After then, we examined hepatotoxicity, nephrotoxicity, inflammation cytokines, expression of inflammation factor mRNA, hemotology, histology through the micro CT-arthrography, and etc. Results : 1. Hepatotoxicity and nephrotoxicity have not expressed. 2. The levels of IL-$1{\beta}$, TNF-${\alpha}$, IL-6, MCP-1, Thromboxane B2, Leukotriene B4, Prostaglandin E2 in serum were significantly decreased. 3. In hematology, the levels of neutrophils and monocytes were significantly decreased. 4. The expression of inflammation factor mRNA like TNF-${\alpha}$ and IL-6, COX-2, iNOS-II were significantly inhibited. 5. In micro CT-arthrography, cartilage volume was less decreased. 6. The degree of osteoarthritis induced damage of joint of BBT group is low in histopathologic observation(hematoxylin&eosin(H&E), Safranin-O). Conclusions : According to this study, BBT has effect of anti-osteoarthritis. Further clinical research for the cartilage protective effect is necessary.

• Korean Journal of Pharmacognosy
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• v.43 no.2
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• pp.167-172
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• 2012

Osteoarthritis (OA) is an age-related joint disease characterized by degradation of articular cartilage and its association with chronic pain. Purified Bee venom (PBV) has been traditionally used to the treatment for inflammatory diseases. The purpose of the current study is to examine whether PBV regulates the pro-inflammation against a mouse model of knee OA induced by papain. We studied the effect of PBV on papain-induced OA in the knee joints of mice. Mice were split into following groups: normal control, papain induced OA, OA treated with PBV, OA treated with meloxicam as positive control. Proteoglycan deposition was analyzed by safranin O-fast green staining and H&E staining. Papain injection significantly degraded the proteoglycan in OA mice at 42 days. Cartilage proteoglycan density was significantly higher in PBV treated OA group than those of the positive control groups. These results demonstrate that PBV efficiently suppresses pathological processes in an OA model. Thus, PBV could be a potential therapeutic strategy for the treatment of OA.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1183-1189
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• 2013

We investigated the effects of oyster shell extract (OSE) on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced in mice by a papain injection into the knee joint. The mice were divided into a total of five groups (n=8). The normal group was untreated, whereas the papain group (negative control) was induced with osteoarthritis and treated with water daily. The papain+DS group (positive control) was treated with diclofenac sodium. Papain+OSE groups were treated with OSE concentrations of 100 and 200 mg/kg/bw for 20 days. Proteoglycan content in articular cartilage was analyzed through safranine-O fast green staining and H&E staining. The histopathological changes in cartilage were measured by the Rudolphi score approach. The contents of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 in plasma were analyzed by the ELISA method. After experiments, body weights of the treated groups were not significantly different compared with the normal group. Cartilage loss and joint instability significantly improved in a dose-dependent manner in the OSE-treated group compared with the papain group (P<0.05). Proteoglycan content was significantly higher in the OSE-treated group than the papain group (P<0.05). Osteoarthritis scores of the OSE-treated group were significantly decreased compared with the papain group (P<0.05). TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 content in the plasma of the papain+OSE treated groups significantly decreased in a dose-dependent manner compared with the papain group (P<0.05). These results suggest that OSE treatment might have anti-arthritic effects on papain-induced osteoarthritis in C57BL/6J mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1510-1518
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• 2014

This study investigated the effects of calcium citrate on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced by injecting $6{\mu}L$ of papain into the knee joints of mice. Calcium citrate was made by crushing the centrifuged precipitate after reacting 0.5 M citric acid with 1 kg of oyster shell extract. The mice were divided into five groups (n=8). The normal group was untreated, whereas the papain group was induced to have osteoarthritis and treated with $200{\mu}L$ of water per day. The papain+DS group was treated with diclofenac sodium. The papain+calcium citrate groups were treated with calcium citrate at 150 and 300 mg/kg/bw for 28 days. Proteoglycan contents in articular cartilages were measured by safranin O/fast green staining and hematoxylin & eosin staining. Histopathological changes in cartilages were analyzed by the Rudolphi score approach. Contents of pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in plasma, were measured by the ELISA method. Body weights among the treated groups were not significantly different compared with that of the normal group. Cartilage loss and joint instability in the calcium citrate group improved significantly (P<0.05) in a dose-dependent manner compared with the papain group. Further, proteoglycan content of the calcium citrate group was considerably (P<0.05) higher than that of the papain group. Osteoarthritis scores in the calcium citrate group were considerably (P<0.05) reduced compared with the papain group. In the group treated with calcium citrate, contents of TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in plasma were significantly (P<0.05) reduced in a dose-dependent manner in comparison with the normal group. Based on these results, we suggest that calcium citrate is effective for treatment of osteoarthritis.

• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.33-52
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• 2012

To evaluate the efficacy of Keonkangbujatang (KKBT) in osteoarthritis treatments, C57BL/10 mice were treated with papain to induce osteoarthritis, and anti-arthritic effects were measured. To ensure safety of the KKBT sample, ALT, AST, BUN, and creatinine levels were measured, and they were all within the normal range. Based on the fact that suppression of inflammatory cytokines leads to the improvement of arthritis, IL-1b, IL-6, TNF-a, and MCP-1 production levels were measured. The cytokines were significantly decreased in serum. Also, mRNA levels of IL-1b, IL-6, and iNOS-II were significantly decreased in joint tissues. PGE2, a usual inflammation vector, and LTB4, TXB2, that are involved in the onset and deterioration of inflammation, were all significantly decreased. The levels of white blood cells, neutrophiles, and mononucleophiles also decreased, although the numbers were not significantly large. I*mmune-modulation of KKBT in the pathological mechanism of cartilage deterioration by inflammatory cells and their vectors was proved. This study should provide basis for the development of effective therapeutics as well as use in clinical practice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.665-671
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• 2012

The purpose of this study is to examine the effect of Vigna angularis ethanol extract (VA-E) on papain induced arthritis in C57BL/10 mice. The C57BL/10 mice were injected with papain and oral administration of Vigna angularis ethanol extract (VA-E) at different doses (100 and 200 mg/kg) once a day for 42 days and compared with untreated mice. Histological examination and the measurement of inflammatory cytokine release were performed. The results showed that comparing with untreated mice, the treatment with Vigna angularis ethanol extract (VA-E) decreased the pathological changes of knee joint tissue. The level of inflammatory cytokine secreted from the tissues, such as IL-$1{\beta}$ (interleukin-$1{\beta}$), IL-6 (interleukin-6), TNF-${\alpha}$ (Tumor Necrosis Factor-${\alpha}$), were decreased. These results were confirmed by the quantification of cartilage volume using micro CT scanning. Consequently, Vigna angularis ethanol extract (VA-E) has a therapeutic potential in inflammatory joint diseases such as osteoarthritis.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.4
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• pp.23-37
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• 2013

Objectives This study was performed to investigate the effects of Saengkanggamchotang (SKT) on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA (50 ul, 60 mg/ml) into knee joints of rats. Rats are divided into a total of 4 groups (normal, control, positive comparison group, SKT treated group, each n=6). Normal group are not treated at all without inducing osteoarthritis whereas control group were induced for osteoarthritis by MIA and oral medicated with 20 ml of distilled water per day. Positive comparison group was injected with MIA and after 7 days, that was taken indomethacin (30 mg/kg/mouse). SKT treated group was injected with MIA and after 7 days that was taken SKT (30 mg/kg/mouse). Positive comparison group and SKT treated group were oral medicated for each substance a total of 4 weeks with one time per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the functions of liver and kidney, Prostaglandin E2, inflammatory cytokine (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), osteocalcin, TIMP-1, MMP-9 within serum. Knee joint structures were observed by H&E, safranin-O staining method, and amount of cartilage were measured by ${\mu}CT$-arthrography. Results 1) Hind paw weight bearing ability was significantly improved. 2) Functions of liver and kidney were not affected. 3) Prostaglandin E2, osteocalcin, TIMP-1, MMP-9 in serum were significantly decreased. 4) Inflammatory cytokine IL-$1{\beta}$ was significantly decreased, and IL-6, TNF-${\alpha}$ were decreased but had not significant. 5) In terms of histopathology, significantly reduced subsidence of cartilage and bone in H&E staining. And in Safranin O staining, proteoglycan content in synovial membrane was significantly increased compared with control group. 6) Destruction of cartilage on ${\mu}CT$-arthrography was significantly reduced. Conclusions Based on all results mentioned above, Saengkanggamchotang (SKT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.6
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• pp.497-503
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• 2010

Purpose: The purpose of this study is to induce artificial arthritis on rabbit TMJ by injecting collagenase. Materials and Methods: An experimental animal model of arthritis induced by surgical method or intraarticular injection of chemical agent like LDH, papain, ketorolac. Surgical method is complex and needs a long time in inducing arthritis. Intra-articular injection of chemical agent like LDH, papain, ketorolac is simple. But chemical agent like LDH, papain, ketololac needs multiple injections to induce arthritis and mechanism inducing arthritis was known. Collagenase destroys helical domain of type II collagen in extracellular matrix produced by chondrocyte and then induces arthritis. We injected collagenase (0.5, 1.0, 2.0 mg) into the temporomandibular joint of rabbit. In the control group saline was intra-articularly injected. The condylar cartilage, disk and synovia were histologically examined at 1, 2, 4, 6 weeks after the initiation of collagenase injections. Results: Four weeks after injection of 2.0 mg collagenase, we could see histologic change like arthritis. In other groups, we couldn't see arthritis-like change. Conclusion: In our study, we produce arthritis on temporomandibular joint of rabbit by using injection of collagenase in temporomandibular joint of rabbit. And this experimental osteoarthritis is a useful animal model.