Effect of Gancao Fuzi Decoction on osteoarthritis and proteomics of articular cartilage in rats / 中国中药杂志

The rat osteoarthritis model was replicated by injection of sodium iodoacetate into the knee joint cavity, and the effects of Gancao Fuzi Decoction on rat osteoarthritis and the proteome of articular cartilage were investigated. Sixty SD rats weighing 230-250 g were randomly divided into normal group, model group, glucosamine sulfate group, and Gancao Fuzi Decoction high, medium and low dose groups. Osteoarthritis model was induced by intra-articular injection of sodium iodoacetate(3 mg on each leg) in all groups except the normal group. After modeling, each administration group was given intragastric administration for 1 month. During the administration period, joint pain test and joint width measurement were performed every week to observe the autonomous behavior of rats. Enzyme linked immunosorbent assay(ELISA) method was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase tissue inhibitor(TIMP-1) in rat joint lavage fluid. Hematoxylin-eosin(HE) staining was used to observe bone and joint morphology. Nano-LC-LTQ-Orbitrap system was used to detect arti-cular cartilage proteins. The results showed that, compared with the model group, Gancao Fuzi Decoction could significantly improve joint pain and joint swelling in osteoarthritis rats, significantly reduce the contents of TNF-α, IL-1β and MMP-3 in the joint cavity la-vage fluid, increase the content of TIMP-1, and relieve inflammatory diseases such as enlarged joint space, rough cartilage edge, different thickness of cartilage layer, and disordered arrangement of chondrocytes. After comparing the proteins between the groups, 273 differential proteins were screened out. KEGG analysis found that the above differential proteins involved 43 signaling pathways such as systemic lupus erythematosus, among which 11 signaling pathways were related to osteoarthritis. The above results indicated that Gancao Fuzi Decoction had a preventive effect on osteoarthritis, and its mechanism of action may be accomplished by regulating the protein expression of osteoarthritis-related signal pathways.

Effects of Locally Delivered Morin Hydrate on Iodoacetate-induced Temporomandibular Joint Osteoarthritis in Rats / Efeitos locais da indução de Hidrato de Morina na articulação temporomandibular de ratos com osteoartrite induzida por Iodoacetato

Objectives: morin hydrate has been reported to possess many beneficial pharmacological potentialities including antioxidant and anti-osteoarthritic effects. The anti-osteoarthritic properties of locally administrated morin have not been investigated. The objective of this study is to evaluate the locally delivered morin on the temporomandibular joint osteoarthritis in rat. Materials and methods: thirty young adult female Sprague Dawley rats were randomly arranged into three groups; control, osteoarthritis and osteoarthritis with morin. Both the iodoacetate for osteoarthritis induction and morin hydrate therapy were delivered unilaterally via intra-articular route. Results: morin reduced osteoarthritis manifestations with prominent thickening of both condylar fibrous layer and articular disc accompanied with discal cells hypertrophy that ultimately acquired chondrocytes features. The condylar cartilage matrix showed enhancement of extracellular matrix production with morin administration. Discussion: the present studyhas elucidated antiosteoarthritic effect of intra articular injection of morin hydrate. Although morin has managed to prevent the propagation and advancing some of the recorded osteoarthritic manifestations; however, it showed some failure in managing others. The administration of morin hydrate modulated the structure of the joint rather than restore it back to its typical configuration. Conclusion: the morin hydrate administration to osteoarthritic animals showed relieve in some of osteoarthritic features and modulated the structure of some joint components to compensate the unhandled manifestations (AU)

Objetivo: Relata-se que o Hidrato de Morina possui diversas potencialidades farmacológicas benéficas, incluindo efeitos antioxidantes e anti-osteoartríticos. As propriedades antiosteoartríticas da morina administrada localmente não foram investigadas. O objetivo deste estudo é avaliar a Morina administrada localmente sobre a osteoartrite da articulação temporomandibular em ratos. Material e métodos: Trinta ratos adultos jovens de linhagem Sprague Dawley foram dispostos aleatoriamente em três grupos: grupo controle, grupo com osteoartrite e grupo com osteoartrite e Morina. Tanto o Iodoacetato para a indução da osteoartrite como a terapia com Hidrato de Morina foram administrados unilateralmente por via intra-articular. Resultados: A Morina reduziu as manifestações da osteoartrite com espessamento proeminente tanto da camada fibrosa condilar como do disco articular acompanhado de hipertrofia das células discais que acabaram por adquirir características condrócitas. A matriz da cartilagem condilar mostrou um aumento da produção de matriz extracelular com administração de Morina. Discussão: O presente estudo elucidou o efeito antiosteoartrítico da injeção intra-articular de Hidrato de Morina. Apesar da Morina ter impedido a propagação e o avanço de algumas das manifestações osteoartríticas registadas, mostrou algumas falhas na manipulação de outras. A administração de Hidrato de Morina modulou a estrutura da articulação em vez de restaurar à sua configuração típica. Conclusão: A administração de Hidratode Morina em animais osteoartríticos mostrou alívio em algumas das características osteoartríticas e modulou a estrutura de alguns componentes da articulação em compensação às manifestações não tratadas. (AU)

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Effect of Electroacupuncture on Cartilage Expression of TypeⅠ Collagen Gene in a Rat Model of MIA-induced Knee Osteoarthritis / 上海针灸杂志

Objective To investigate whether inhibiting the expression of typeⅠ collagen gene is one of the mechanisms of action of electroacupuncture in improving knee osteoarthritis.Methods Forty male adult SD rats were randomized into normal, model, medication and electroacupuncture group, 10 rats each. A rat model of MIA-induced knee osteoarthritis was made by injecting monomer sodium iodoacetate (MIA) and driving rat movement. After model making, the medication group received an oral gavage of celecoxib dissolved in 10% DMSO and the electroacupuncture group, electroacupuncture at points Zusanli and Yanglingquan. Pain thresholds and the levels of cartilage expression of typeⅠ collagen mRNA were compared between various groups of rats before and after treatment.Results There was a statistically significant difference in pain threshold between the model, medication or electroacupuncture group of rats and the normal group after model making (P0.05). There was a statistically significant difference in the expression of typeⅠ collagen mRNA between the model, medication or electroacupuncture group of rats and the normal group (P0.05).Conclusion The mechanisms of actions of electroacupuncture and medication in treating knee osteoarthritis may be related to inhibiting the expression of typeⅠ collagen mRNA.

Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats / 한국실험동물학회지

The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1β and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1β, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose-dependent manner.

Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats.

Background & objectives: Osteoarthritis (OA) is a degenerative disease characterized by joint pain and progressive loss of articular cartilage. Entada pursaetha has been traditionally used in the treatment of inflammatory disease, liver ailment, etc. In this study we investigated suppressive effect of ethanolic extract of E. pursaetha (EPE) on monosodium iodoacetate (MIA)-induced osteoarthritis pain and disease progression by histopathological changes in joints in a rat model. Methods: OA was induced in right knee of rat by intra-articular injection of 3 mg of MIA and characterized by pathological progression of disease and pain of affected joint. Spontaneous movements, mechanical, thermal and cold sensitivity were monitored at days 0 (before drug and MIA injection), 7, 14 and 21 of MIA administration. EPE (30, 100 and 300 mg/kg), vehicle or etoricoxib (10 mg/ kg; reference drug) were administered daily for 21 days by oral route. Results: EPE at various doses significantly reduced mechanical, heat, cold hyperalgesia and increased the horizontal and vertical movements in intra-articular MIA injected rats. EPE prevented the damage to cartilage structure and reduced the cellular abnormalities. Articular cartilage of rats treated with EPE at 300 mg/kg group was almost normal with well-developed smooth surface and chondrocytes were distributed individually or arranged in column. Interpretation & conclusions: the present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.

Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

Hyaluronic acid with or without bone marrow derived-mesenchymal stem cells improves osteoarthritic knee changes in rat model: A preliminary report.

Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that its progression can be reduced by the use of hyaluronic acid (HA) or mesenchymal stem cells (MSC). The present study thus aims to examine the effects of MSC, HA and the combination of HA-MSC in treating OA in rat model. The histological observations using O’Driscoll score indicate that it is the use of HA and MSC independently and not their combination that delays the progression of OA. In conclusion, the preliminary study suggest that the use of either HA or MSCs effectively reduces OA progression better than their combined use.

Evaluation of antiarthritic and immunomodulatory activity of Barleria lupulina

Objective: Barleria lupulina Lindl (Acanthaceae) (B. lupulina) has been traditionally used in the treatment of rheumatoid arthritis but, no scientific data has been published supporting the claimed ethnomedical use. This study was designed to investigate the anti-arthritic potential of B. lupulina leaves and its role in immunomodulation. Methods: Methanol extract of B. lupulina (MEBL) leaves (300 and 600 mg/kg BW) was tested for its antiarthritic activity by various models namely, formalin-induced arthritis, adjuvant induced arthritis, collagen type II-induced arthritis and monosodium iodoacetate induced osteoarthritis. Immunomodulatory activity of the same was tested by measuring WBC Count, Spleen Weight, Spleen WBC Count and Delayed Type Hypersensitivity (DTH) Reaction.Results:MEBL extracts 300 mg/kg and 600 mg/ kg showed statistically significant inhibition (P<0.05 and P<0.001) of the edema formation and Myeloperoxidase (MPO) during experimental period and activities of antioxidants were restored significantly. MEBL extracts 300 mg/kg and 600 mg/kg significantly increased the Hemoglobin (Hb) level, serum albumin, total protein, calcium and phosphorus levels and reverted back the levels of WBC count and Erythrocyte Sedimentation Rate (ESR) (P<0.05 and P<0.01). Histopathological studies of ankle joints also supported this finding. Immunomodulatory study revealed an increase in the blood leukocytes count, weight of spleen, spleenic leukocytes count and increase in paw volume on delayed type hypersensitivity footpad thickness suggesting an uplift of immune status. Conclusions: The present study concluded that, MEBL holds antiarthritic and Immunomodulatory activity. Although subsequent study is required to evaluate the active constituents responsible for the activity.