AIF has been formulated using three herbs known to have anti-inflammatory and anti-osteolytic effects. In this study, the potential therapeutic effects of AIF for osteoarthritis were assessed in vitro and in vivo. The effects of AIF on the cartilage and bone protection (MMP-13 expression, GAG degradation, OPG release) were examined, in vitro. In addition, the therapeutic effect of AIF was evaluated using a chemical-induced osteoarthritis rat model. Rats were injected with iodoacetate intraarticularly in one knee joint and treated with the oral administration of 100 mg/kg AIF-glucosamine once a day for 3 weeks. And then, destruction of cartilage and bone was evaluated by histopathological assessment. AIF significantly inhibited the production of MMP13 and GAG in a dose dependent manner in vitro. Also, AIF increased the production of OPG. In OA rat model, the AIF-glucosamine treated group reduced cartilage destruction, compared to vehicle or glucosamine treated group. AIF showed potent protective effects for the destruction of cartilage and bone, in vitro and in vivo. These results suggest that AIF contains effective compound(s) which may modify the progression of arthritis.
Objectives : The purpose of this study was to evaluate the effects of Daeganghwal-tang on knee cartilage in monosodium iodoacetate(MIA)-induced osteoarthritis rats. Methods : Forty SD rats were randomly divided into five groups(n=8/group): normal group was SD rats group injected with normal saline at left knee joint and administrated orally distilled water, control group was MIA-induced osteoarthritis SD rats group administrated orally distilled water, Indomethacin group was MIA-induced osteoarthritis SD rats group administrated orally indomethacin 2 mg/kg, DGHT(L) group was MIA-induced osteoarthritis SD rats group administrated orally 1280 mg/kg of Daeganghwal-tang, and DGHT(H) group was MIA-induced osteoarthritis SD rats group administrated orally 2560 mg/kg of Daeganghwal-tang. After orally administration of drugs for 4 weeks, gross appearance and histological analysis were used to evaluate the degree of knee cartilage damage. In addition, pro-inflammatory cytokines, bone degrade factor and bone defence factors were analyzed to investigate the anti-inflammatory and cartilage protection effects of Daeganghwal-tang. Also, hematological test, biochemical test, and liver and kidney tissue were analyzed to determine the safety of Daeganghwal-tang. Results : Daeganghwal-tang inhibited the damage of the knee cartilage, and significantly prevented the reduction in cartilage thickness. In addition, the pro-inflammatory cytokines and the bone degrade factor significantly decreased, and the bone defence factors significantly increased. In the safety assessment of Daeganghwal-tang, there were no significant differences among the experimental groups and no abnormal findings were observed. Conclusions : Daeganghwal-tang has anti-inflammatory effect, inhibits cartilage damage, and protects cartilage in MIA-induced osteoarthritis rats.
Osteoarthritis is characterized by cartilage degradation and chondrocytes death. Chondrocyte death is induced by the apotosis through special mechanisms including the activation of caspase-3. On the basis of this background, this study was designed to examine the cartilage protective and anti-apototic effects of Aralia Cordata in in vtro and in collagenase-induced arthritis rabbit model. To conduct in vitro study, chondrocytes culturedfrom rabbit knee joint were treated by 5 ng/ml IL-1a.For in vivo experiment, collagenase-induced arthritis (CIA) rabbit model was made via intraarticular injection with 0.25 ml of collagenase solution. Aralia cordata pharmacopuncture (ACP) was administrated on bilateral Dokbi acupoint (ST35) of rabbits at a dosage of 150 ${\mu}g/kg$ once a day for 28 days after the initiation of the CIA induction. In the study by using CIA rabbit model in vivo, ACP showed the inhibition of cartilage degradation in histological analysis. Aralia cordata also showed anti-apoptotic effect both in vitro and in vivo study. In chondrocytes treated by IL-1a, Aralia cordata inhibited caspase-3 activity and enhanced the proliferation of IL-1a-induced dedifferentiated chondrocytes. ACP showed the inhibition effect on the caspase-3 expression and activity from CIA rabbit model. This study indicates that ACP inhibits the cartilage destruction and the chondrocyte apotosis through downregulation of caspase-3 activity. These data suggest that ACP has a beneficial effect on preventing articular cartilage destruction in osteoarthrtis.
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.
Objectives : To research trends of studies on treatments of knee osteoarthritis in Korean medicine. Methods : Domestic theses, published from 2000 to 2010, mentioning the treatments of knee osteoarthritis in Korean medicine were reviewed and analyzed. This study researched 79 theses and classified again according to the fields of the treatment. Results : The results were obtained as below ; 1. Studies on pharmacoacupuncture account for 41% of the total (32cases/79cases). The target of treatments had changed from pain alleviation and anti-inflammation to cartilage-protection since 2006. 2. Herbal Drug, Bee Venom, Cervi Cornu Parvum pharmacoacupuncture, Taping Therapy and Tai-Chi Exercise program were more effective than others. Moreover research on exercise program such as Tai-Chi has been increasing. 3. Some Herbal Drug (Glycyrrhizae Radix, Angelicae Gigantis Radix, Achyrantis Radix, Paeoniae Radix, Eucommiae Cortex and so on) were mainly used to investigate the effect on cartilage protection, pain relief and anti-inflammation in laboratory test. 4. Acupuncture including individualized, local acupoints and constitution acupuncture were effective than others in pain alleviation and symptom relief. 5. Pharmacoacupuncture Bee Venom were effective in recovery of joint function and pain relief while Buthus martensii Karsch, Homnis Placenta and Cervi Cornu Parvum were effective in cartilage protection and recovery. 6. Moxibustion was efficient to reduce joint pain and partly increase ROM (range of motion) of knee joint, but was not efficient to recover the function of knee joint. Conclusions : These results indicate that research trends on knee osteoarthritis were changed from symptomatic treatment (pain alleviation and anti-inflammation) to conservative treatment (cartilage protection and recovery).
Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycanand collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Cinnamomum cassia in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit and human articular cartilage explants. Methods: The cartilage-protective effects of Cinnamomum cassia were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results: Interleukin-1a (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Cinnamomum cassia significantly inhibited GAG and collagen release in a concentration-dependent manner. Cinnamomum cassia dose-dependently inhibited MMP-1, MMP-3 and MMP-13 activities from IL-1a-treated cartilage explants culture when tested at concentrations ranging from 0.02 to 1 mg/ml. Conclusion : These results indicate that Cinnamomum cassia inhibits the degradation of proteoglycan and collagen through the down regulation of MMP-1, MMP-3 and MMP-13 activities of IL-1a-stimulated rabbit and human articular cartilage explants.
Kim, Ji-Hun;Yun, Sungho;Seo, Min-Su;Bae, Seulgi;Jang, Min;Ku, Sae-Kwang;Kwon, Young-Sam;Lee, Hae Beom
한국임상수의학회지
/
제37권5호
/
pp.261-269
/
2020
The purpose of this study is to investigate the clinical effects of carboxymethyl chitosan (CMC) and adipose-derived mesenchymal stem cells (MSCs) on osteoarthritis (OA). Thirty New Zealand white rabbits were used as cranial cruciate ligament transection and partial meniscectomy models. The rabbits were divided into five groups (n = 6) according to the intra-articular injection materials: the control group with PBS, the HA group with hyaluronic acid, the CMC group with CMC, the MSC group with MSCs emerged in PBS, and the MSC+CMC group with CMC and MSCs. Knee thickness, extension angle, gross morphology, histopathology and immunohistochemistry were performed to evaluate the effects of CMC and MSCs on rabbit OA. On the morphologic and histologic examination, the articular surfaces of the femur and tibia were markedly damaged in control group with higher Mankin score and lower cartilage surface thickness. However, OA related cartilage defects were alleviated by the treatment of MSC and/or CMC. The expressions of apoptotic and inflammatory cytokines were decreased and cartilage extracellular matrix (ECM) related collagens I and II were enhanced by the treatment of MSC and/or CMC. In conclusion, this study showed that CMC and MSC treatments have a beneficial effects on OA via the protection of cartilage damage, the stimulation of ECM, and the inhibition of inflammatory and apoptotic reaction.
Objectives : This study was planned to evaluate the therapeutic effectiveness and possible underlying mechanism of TPE (Tetrapanax papyrifer stem(inner part of the stem Extract) and AQE (Akebiae quinata stem Extract) on osteoarthritis. Methods : Osteoarthritis models were induced through intra-articular injection of MIA (monosodium iodoacetate) 50 μL with 80 mg/ml in rats. Excluding the normal group, Osteoarthritis-induced rats were divided into 4 groups (Control, INDO, TPE, AQE). The drug concentrations were indomethacin 5 mg/kg, TPE 200 mg/kg, and AQE 200 mg/kg, and were orally administered once a day for a couple of weeks. After drug supplementation, the effects of TPE and AQE were measured with serum diagnosis, western blotting, and histopathological staining. Results : It was found that the DPPH and ABTS free radical erasure ability of AQE was better than that of TPE. AQE administration improved rear limb overload and it led to relieving pain. Both PTE and AQE significantly reduced the expression of inflammatory mediators COX-2, iNOS, and inflammatory cytokine IL-1β and IL-6 by inhibiting the phosphorylation of IκBα and deactivating the pathway of NF-κBp65. On the other hand, TNF-α was significantly reduced only by administration of AQE. In addition, histopathological analysis showed that the administration of AQE compared to PTE suppressed cartilage degeneration and effectively suppressed damage to proteoglycan, a component of ECM. Conclusion : Reviewing these experimental results, TPE and AQE possessed the effect of delaying the progress of osteoarthritis and protecting cartilage. In addition, the results of this study show that AQE has a better cartilage protection effect than TPE.
Objectives : This study was designed to investigate the effects of Sunbanghwalmyung-eum gamibang on Monosodium iodoacetate-induced osteoarthritis rats. Methods : Forty Sprague-Dawley (SD) rats were divided into 5 groups of 8 rats each. Osteoarthritis (OA) was induced by injecting MIA (2 mg/50 µl) into the joint cavity of the left knee of SD rats belonging to the experimental group, and normal saline was injected into the joint cavity of the left knee instead of MIA in the normal group. To the normal group and the controlled group (OA group), 2 ml of distilled water was orally administered. To the positive control group (Indomethacin group), indomethacin 2 ml at a concentration of 2 mg/kg, to the low concentration group of SHG (Low group), 2 ml of SHG at a concentration of 2 mg/kg, and to the high concentration group of SHG (High group), 2 ml of SHG at a concentration of 4 mg/kg ml was orally administered. The drug was administered for a total of 4 weeks, and histological changes were analyzed by Hematoxylin-Eosin staining and Safranin-O staining. In addition, inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and MMP-13, TIMP-1, and GAGs were immunohistochemically analyzed. Finally, hematological examination, blood biochemical examination, and liver and kidney biopsy were performed. Results : SHG groups (Low and High) inhibited the matrix destruction and damage of the knee joint cartilage in SD rat model, and significantly prevented the reduction in cartilage thickness. In SHG groups, the expressions of TNF-α, IL-1β, IL-6 and MMP-13 were significantly decreased, and the expressions of TIMP-1, GAGs were significantly increased compared with OA group. The safety indicators had no significant differences among five groups. Conclusions : These results show that SHG has cartilage protection capacity, anti-inflammatory effect.
Rheumatoid arthritis is a chronic, systemic, and inflammatory autoimmune disorder that affects 1% of the adult population worldwide. Osteoarthritis is a multifactorial disease with high morbidity that is characterized by degradation of the matrix and destruction of articular cartilage. In this study, we examined the inhibition effect of Trachelospermi Caulis on the inflammation($TNF-{\alpha}$, $IL-1{\beta}$, NO), cartilage protection(MMP-13), and cell death in arthritis. RAW 264.7 and SW 1353 cells were cultivated in DMAE(GibcoBRL, USA) with 5% FBS and Fungizone in $37^{\circ}C$, 5% CO2. THP-1 cells were cultivated in RPMI(GibcoBRL, USA) with 5% FBS and Fungizone in $37^{\circ}C$, 5% CO2. Activity of caspase-3, XIAP, Cytochrome C in the cell was examined by using western blot. The results obtained were as Follows; Concentration of nitric oxide in Trachelospermi Caulis treatment group significantly decreased compared with that of non-treatment group (P<0.05). In treated group, Concentration of Trachelospermi Caulis was not significantly associated with cell death. Concentration of $TNF-{\alpha}$ and $IL-1{\beta}$ in Trachelospermi Caulis treatment group decreased significantly compared with that of none treatment group (P<0.05). Relative density of MMP-13 in Trachelospermi Caulis treatment group decreased significantly compared with that of none treatment group and dose-response relationship was observed. After treatment of staurosporin in SW1353 which increases cell death, in Trachelospermi Caulis treated group, the cell death was effectively decreased. In conclusion, these results suggest that Trachelospermi Caulis inhibit inflammation and cell death in arthritis. More researches about effect of Trachelospermi Caulis are considered to need.
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