• Journal of Yeungnam Medical Science
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• v.19 no.1
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• pp.39-48
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• 2002

Background: The treatment of rheumatoid arthritis still depend on conserve therapy in major. Recent studies report that n-3 polyunsaturated fatty acids(PUFA) could modulate the incidence and progress of arthritis. The purpose of this study was to investigate the effects of n-3 PUFA on the development of collagen-induced arthritis in rats. Materials and Methods: Female Louvain rats were used for this experiment. Rats were randomly assigned into either normal (n=8) or collagen-immunized groups, and collagen immunized groups were divided into control(n=8, normal diet) and n-3 PUFA(n=8, 5% n-3 PUFA in diet) groups. One week after feeding n-3 PUFA to rats, they were immunized with type II collagen emulsified in incomplete Freund's adjuvant into tail and back. Development of arthritis was confirmed by x-ray and microscopic examination. Results: Incidence of arthritis at the 5th week after immunization was 38% in control and 0% in n-3 PUFA. Rats with arthritis showed edema in hind paws and inflammation in synovial membrane of the knee joint. Plasma glucose and insulin were not changed by both of immunization and diet. Plasma triglycerides and cholesterol concentrations were decreased by n-3 PUFA. Conclusion: n-3 PUFA may prevent or treat collagen-induced arthritis m rats. Further studies are needed for action mechanism of it.

• Journal of Microbiology and Biotechnology
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• v.28 no.7
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• pp.1199-1208
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• 2018

Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• The Journal of Korean Academy of Orthopedic Manual Physical Therapy
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• v.2 no.1
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• pp.9-19
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• 1996

Type I, II, III are regarded as "true" joint receptors, type IV is considered a class of pain receptor. Type I, II and III mechanoreceptors, via static and dynamic input, signal joint position, intraarticular pressure changes, and the direction, amplitude, and velocity of joint movements. Type I mechanoreceptor subserve both static and dynamic physiologic functions. Type I are found primarily in the stratum fibrosum of the joint capsule and ligaments. Type I receptors have a low threshold for activation and are allow to adapt to changes altering their firing frequency. Type II receptors have a low threshold for activation. These dynamic receptors respond to joint movement. Type II receptors are thus termed rapidly adapting. Type II joint receptors are located at the junction of the synovial membrane and fibrosum of the joint capsule and intraarticular and extraarticular fat pads. Type III receptors have been found in collateral ligaments of the joints of the extremities. Morphologically similar to Golgi tendon organ. These dynamic receptors have a high threshold to stimulation and are slowly adating. Type IV receptors possess free nerve ending that have been found in joint capsule and fat pads. They are not normally active, but respond to extreme mechanical deformation of the joint as well as to direct chemical or mechanical irritation. Small amplitude oscillatory and distraction movements(joint mobilization) techniques are used to stimulate the mechanoreceptors that may inhibit the transmission of nociceptors stimuli at the spinal cord or brain stem levels.

• Herbal Formula Science
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• v.29 no.2
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• pp.81-91
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• 2021

Objectives : This study was conducted to evaluate the efficacy of a complex mixture of natural substances of ginseng and baeknyeoncho on the arthritic rats. Methods : In vitro experiments were conducted to ensure the stability of the complex. After setting toxicity and concentration by MTT assay, the antioxidant effect was measured through DPPH and ABTS radical scavenging activity. To confirm the anti-inflammatory effects of the complex, levels of nitric oxide (NO) and pro-inflammatory cytokines (IL-1β, TNF-α) were measured in LPS-treated macrophage cell lines (RAW264.7). We injected monosodium iodoacetate (MIA) 50 μl (60 mg/ml) into knee joints of rats to induce osteoarthritis. The rats were divided into three groups (normal (n=5), control (n=5), and OR (n=5) group). The control group consumed 2 mg/kg of physiological saline once a day for 4 weeks, and the OR group was mixed at a concentration of 416.5 mg/kg of Baengnyeoncho (O) and 208.25 mg/kg of red ginseng (R) and ingested 1 mL each 5 days a week. Results : This complex increased the DPPH and ABTS radical scavenging rate. The complex decreased NO production and pro-inflammatory cytokine production of macrophages. In the OR group, the secretion of cytokine in serum was decreased. In histopathological examination, the joint tissue of the composite showed less damage to the synovial membrane, cartilage, and fibrous tissue than the control group. Conclusions : As a result of this study, natural complexes have antioxidant, anti-inflammatory and cartilage protection effects. Therefore, we expect the complex to be effective in treating osteoarthritis.

• Journal of the Korean Applied Science and Technology
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• v.38 no.2
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• pp.368-377
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• 2021

The present study aimed to evaluate the effects of radiation mutant Perilla frutescens var. crispa and Atractylodes macrocephala Koidzumi complex extract(Perilla frutescens var. crispa complex extract) on the mediators related to degenerative arthritis in a monosodium iodoacetate-induced rat model of degenerative arthritis. Perilla frutescens var. crispa complex extract was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 µl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral Perilla frutescens var. crispa complex extract for another 4 weeks. It was evaluated that the treatment effects based on serum bio-markers, and morphological and histopathological analysis of the knee joints. Compared with those in negative control rats, the Perilla frutescens var. crispa complex extract treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., TNF-α, MMP-3, COX-2, PGE₂, COMP, and Aggrecan). Otherwise, it was significantly increased the production of CTX-2 in cartilage absorption mediators. In addition, the Perilla frutescens var. crispa complex extract treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that the Perilla frutescens var. crispa complex extract improved degenerative arthritis symptoms. Thus, the Perilla frutescens var. crispa complex can be used in food material for the management of degenerative arthritis.