• Journal of Korean Medicine Rehabilitation
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• v.27 no.4
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• pp.33-53
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• 2017

Objectives This study was designed to review animal studies about the efficacy of herbal medicine for Rheumatoid arthritis animal model which was published in Korea after 2008. We also systematically investigated the reporting quality of the animal studies. Methods We systematically searched original articles in 8 databases since 2008. And manual searching was conducted through 10 Korean medicine journals from 2008. Studies were included if they used animal experimental model(s) with orally administered herbal medicine. Data were extracted regarding animal model, rheumatoid arthritis indicator and detail of intervention. Reporting quality of each study was also assessed by the STARA and ARRIVE guidelines. Results Nine hundred two articles were screened. Finally, 35 articles were included. 35 studies all showed that the herbal medicine used in the studies has significant effect on alleviating the macroscopic indicators, hematological indicators, histological indicators, genetic indicators, osteological indicator of Rheumatoid Arthritis and others. Species of animals was reported in 100% while ventilation and noise were reported in 0% in STRASA guidelines. Ethical statement was reported in 42.9%, experimental animals and sample size were reported in 24%, 29% and there was no study reporting funding. Conclusions These results suggest that herbal medicine might be effective treatment for Rheumatoid Arthritis. It should be improved by clinical studies. And there is a need for studying about efficacy and safety of each specific herbal medicine. And we should improve the Reporting quality of the animal studies published in Korea.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.104-112
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• 2012

The fruit of Terminalia chebula Retzius has been used as a panacea in India and Southeast Asia but its biological activities have not been fully elucidated. Here we report anti-arthritic and analgesic effect of NDI10218, a standardized ethanol extract of Terminalia chebula, on collagen-induced arthritis and acetic acid-induced writhing model, respectively. Arthritis was induced in DBA/1J mice by immunizing bovine type II collagen and mice were treated with NDI10218 daily for 5 weeks after the onset of the disease. NDI10218 reduced the arthritis index and blocked the synovial hyperplasia in a dose-dependent manner. The serum levels of pro-inflammatory cytokines TNF-${\alpha}$, IL-6, and IL-$1{\beta}$ were significantly reduced in mice treated with NDI10218. Production of the inflammatory IL-17, but not immunosuppressive IL-10, was also inhibited in splenocytes isolated from NDI10218-treated arthritis mice. Administration of NDI10218 markedly decreased the number of T cell subpopulations in the regional lymph nodes of the arthritis mice. Finally, NDI10218 reduced the number of abdominal contractions in acetic acid-induced writhing model, suggesting an analgesic effect of this extract. Taken together, these results suggest that NDI10218 can be a new therapeutic candidate for the treatment of rheumatoid arthritis.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.368-384
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• 1998

To know the effects of Gentiana macrophylla(GM) on the immune response, this study was undertaken. GM is one of the well-known oriental medicines for a lomg time used for the treatment of such diseases as arthralgia, headache, hepatitis, SLE, hemiparesis, and so on. To evaluate the effects of GM on immune response in the collagen induced arthritis, phagocytic activity of macrophages, proliferation of T-lymphocytes, secretion of nitric oxide in urine, and production of ROIs, $TNF-{\alpha}$ and nitric oxide in synoviocytes were measured. The results obtained in this study were as follows: 1. During the progress of CIA, the administration of GM enhanced phagocytic activity of macrophages in vivo and vitro. 2. During the progress of CIA, the administration of GM inhibited production of ROIs in synoviocytes. 3. During the progress of CIA, the administration of GM inhibited production of TNF- a in synoviocytes. 4. During the progress of CIA, the administration of GM inhibited proliferation of T lymphocytes. 5. During the progress of CIA, the administration of GM inhibited production of nitric oxide in synoviocytes. 6. During the progress of CIA, the administration of GM inhibited secretion of nitric oxide in urine. According to the above results, during the progress of CIA, it might be considered that GM has a curative effect on rheumatoid arthritis by controling immune response.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.45.1-45.13
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• 2021

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye^® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

• 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.

• The Journal of Korea CHUNA Manual Medicine
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• v.4 no.1
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• pp.75-88
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• 2003

Objectives : The purpose of this study is to find out the effects of Catalpa Ovata on the collagen-induced arthritis in the lewis rats. and we infere the effects of Catalpa Ovata on the rheumatoid arthritis in the human body. Methods : We investigated the effect of Catalpa Ovata on the Collagen-induced arthritis in Lewis rats via morphology, histology and serology as an experimental group, a control group, and a normal group. We feed Catalpa Ovata. only to an experimental group. Results : According to this research, the abnormal finding In Moire topography was 53.7% (1,018 students), and students needed X-ray re-examination were 11.2% (213 students). Students diagnosed scoliosis by X-ray re-examination were 1.8%. According to statistical analysis, interval between vertical base line of pelvis and vertical base line of neck, gap between left distance and right distance to the vertical base line of pelvis and difference of contour lines have strong correlations with deformity degree of the body surface examined by Moire. Conclusions : 1. The weight of an experimental group were lower than control group with statistically significant at 15 days later. 2, The paw edema volume of an experimental group were lower than control group at 10 days, 15 days later. but couldn't be found meaning. 3. The size of the tarsal joint of an experimental group were lower than control group at 5 days, 10 days, 15 days later, but couldn't be found meaning. 4. The volume of tumor necrosis factor-a at an experimental group were lower than control group with statistically significant. 5. The volume of interleukin-$1{\beta}$ at an experimental group were lower than control group with statistically significant. 6. An experimental group and a control group were showed ankylosing osteoarthritis, but an experimental group compared with a control group, alleviated In the fibrous ankylosis, destruction of articular cartilage and destruction of subchondral bony tissue. According to the above results, it might be considered that Catalpa Ovata has the suppression of the advance of the Collagen-induced arthritis and that result were presumed to bo connected with suppression of volume of the tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in the blood.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.1
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• pp.37-59
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• 2010

Objectives : The object of this study was to observe the favorable anti arthritic effects of Euiiin-tang($y{\grave{i}}y{\breve{i}}r{\acute{e}}n-t{\bar{a}}ng$) aqueous extract(EIITe), has been traditionally used in Korean medicine for treating rheumatoid arthritis on collagen induced arthritic(CIA) DBA/1 mice. Methods : In the present study, effects of EIITe on the releases of human tumor necrosis factor(TNF)-${\alpha}$, interleukin(IL)-$1{\beta}$, matrix metalloproteinase(MMP)-13 and production of Nitric oxide(NO) were observed by in vitro. In addition, to observe the effects on the CIA mice, three different dosages of EIITe, 300, 150 and 150 mg/kg were orally administered once a day for 18 days from 24hrs after antigen challenges(type II collagen) on 21 days after immunization using Type II collagen Freund's complete adjuvant. Six groups, each of 8 DBA/1 mice per group were used in the present study as follows. Changes on the body weights, macroscopic arthritis scores, splenic weights, splenic TNF-${\alpha}$ and IL-6 contents, articular cartilage(femur and tibia) collagen and glycosaminoglycans-chondroitin sulphate, sulphate and hyaluronic acid contents, histopathological observations(microscopic arthritis scores, thicknesses of femur and tibia cartilage thicknesses were monitored, compared to that of dexamethasone, a potent anti inflammatory agents, 1 mg/kg treated mice. Results : As results of collagen challenges, marked decreases of body weights and gains, articular cartilage collagen and glycosaminoglycan - chondroitin sulphate, sulphate and hyaluronic acid contents were observed with increases of macroscopic arthritis scores, splenic weights, splenic TNF-${\alpha}$ and IL-6 contents, articular cartilage(in the both femur and tibia) loss and damages. However, these CIA signs were significantly and dosages dependently inhibited by treatment of EIITe 300 and 150 mg/kg as compared with CIA control, respectively. In addition, the releases of TNF-${\alpha}$, IL-$1{\beta}$, NO and MMP-13 were markedly and dose dependently inhibited by treatment of EIITe, invitro. Although CIA were more favorably inhibited by treatment of dexamethasone 1 mg/kg as compared with EIITe 300 mg/kg, marked decreases of body weights were detected in dexamethasone 1 mg/kg treated mice. Conclusions : The results obtained in this study suggest that over 150 mg/kg of EIITe showed favorable anti arthritic effects on the CIA mediated by immunomodulatory and/or anti oxidative effects. However, detail mechanism studies should be conduced in future with the screening of the biological active compounds in this herb. lthough CIA were more favorably inhibited by treatment of dexamethasone 1 mg/kg as compared with EIITe 300 mg/kg, marked decreases of body weights were detected in dexamethasone 1 mg/kg treated mice, in the present study.

• Journal of Microbiology and Biotechnology
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• v.27 no.10
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• pp.1892-1895
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• 2017

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.

• Journal of Acupuncture Research
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• v.25 no.1
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• pp.25-55
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• 2008

Objectives : The aim of the present study was to observe the effect of Astragali Radix Herbal-Acupuncture Solution(AR-HAS) at $ST_{36}$(jok-samni, $Z\acute{u}s\bar{a}n$ Li) on collagen- II -induced arthritis(CIA) in mice. Methods : DBA/1J mice were immunized with bovine type II collagen(CII) on days 0 and 21 to induce arthritis. The mice were divided into 5 groups : normal group(no CIA), control group(CIA+no treatment), needle prick group(CIA+single prick with an injection needle), saline group(CIA+saline injection) and ARHA group(CIA+ R-HA treatment). The needle prick, saline injection, and AR-HA groups were injected on the right $ST_{36}$(jok-samni) of mice for 9 weeks, 3 times a week, beginning 4 weeks after the booster immunization. Results : 1. The incidence of arthritis, AI(arthritis index), and joint edema decreased in the AR-HA group. 2. Weight gain, hypertrophy of the spleen, adhesion of the tissues, and transformation of the joint were restrained in the AR-HA group. 3. The concentrations of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in CIA mouse serum and $IFN-{\gamma}$, IL-10 in the CIA mouse spleen cell culture decreased significantly at $ST_{36}$ in the AR-HA group. 4. Total cell counts increased significantly, and the ratio of $CD3e^+$ to $CD45R^+$, $CD4^+$ to $CD8^+$, and $CD4^+$ to $CD25^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse spleen cell culture of the AR-HA group. 5. Total cell counts decreased significantly, and $CD4^+/CD25^+$ and $CD45R^+/CD69^+$ decreased significantly at $ST_{36}$ in the CIA mouse lymph nodes of the AR-HA group. 6. $CD3e^+/CD69^+$ and $CD11b^+/Gr-1^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse joints of the AR-HA group. 7. The histological examination showed that cartilage destruction and synoviocyte proliferation decreased in the CIA mouse joints of the AR-HA group, and collagen fiber was expressed similar to that seen in the normal group. Conclusions : Our experiments show that at $ST_{36}$, an anti-inflammatory mechanism of AR-HA controls synovial cell proliferation and protects against cartilage destruction in rheumatoid arthritis.

• Journal of Acupuncture Research
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• v.24 no.6
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• pp.1-14
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• 2007

Backgrounds : Rheumatoid Arthritis(RA) is known as the chronic inflammatory diseasethat induces persistent inflammation in the joint cavity. The destruction of cartilage occurs as the result of bones destoyed by pannus, several influential cytokines induced by the synovial capsulitis, varieties of proteinases, $O_2$ radicals, and the secondary degenerative changes of articular cartilage. The type 2 collagen-induced arthritis model is used in recent experimental research on rheumatoid arthritis. Cervus elaphus sibiricus (Nockyong) has the effect of relieving pain by nourishing the muscles, joints, and bones. It is also known to be efficacious in promoting and enhancing the immune system. The objective of this study was to investigate the effect of Cervus elaphus sibiricus herbal acupuncture to inhibit the generation of proinflammatory enzyme on type 2 collagen-induced arthritis. I investigated the inhibition of mRNA transcription of MIF(macrophage migration inhibitory factor), $TNF-{\alpha}$(Tumor necrosis $factor-{\alpha}$) and MMP-9 (matrix metalloproteinase-9) of Cervus elaphus sibiricus herbal acupuncture using an in vitro test. Also investigated was the inhibition of differentiation of Th 1 cells and activation of cytokines(MIF, $TNF-{\alpha}$, IL-6, MMP-9), which are known to cause initial RA ,and are also related to the morphology of the synovial membranes of the joint capsule, by an in vivo test, using CIA(collagen induced arthritis) model mice. Materials & methods : The laboratory animals used in this experiment were 4 week-old DBA female mice, weighing approximately 20 grams, and adjusted to the laboratory environment. The experiment was divided into the normal group(NOR)-no treated group, control group(CON)-CIA induced group, and sample group(SAM)-Cervus elaphus sibiricus herbal acupuncture treated group. RA was induced in the mice via injection of $50{\mu}{\ell}$ C II mixed CFA. The Cervus elaphus sibiricus herbal acupuncture solution was applied on $GB_{35}$(陽陵泉) for 26 days from the 3rd day of RA inducement. The concentration of the solution was determined via a MTT assay. To research the effect on the expression of MIF, $TNF-{\alpha}$ and MMP-9 mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. C II induced RA knee joint's histo-chemical synovial membrane was observed using a specimen model via the Hematoxilin and Eosin dying technique. Results : The expression of mRNA of RA-related cytokines such as MIF, $TNF-{\alpha}$, and MMP-9 dosedependently decreased in the cell from the synovial membranes of the joint, which is treated with Cervus elaphus sibiricus herbal acupuncture solution. In mice treated with Cervus elaphus sibiricusherbal acupuncture, the damage of synovial membranes of the joint was lessened, and differentiation of Th 1 cells was suppressed. The activation of RA-related cytokines such as MIF was suppressed, and the generation of $TNF-{\alpha}$ and MMP-9 showed a statistically significant decreas. Conclusions : It is speculated that Cervus elaphus sibiricus herbal acupuncture has the therapeutic effect of palliating the damage of the tissue impaired by RA by inhibition of the initial RA progression and by regulating excessive differentiation of Th 1 cell as it suppresses the generation of RA-related cytokines during the highest stage of RA by acting on pro-inflammatory enzymes.