Protective Effects of an Oligo-Fucoidan-Based Formula against Osteoarthritis Development via iNOS and COX-2 Suppression following Monosodium Iodoacetate Injection.

Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this study, we utilized the monosodium iodoacetate (MIA)-induced OA model to investigate the efficacy of oligo-fucoidan-based formula (FF) intervention in mitigating OA progression. Through its capacity to alleviate joint bearing function and inflammation, improvements in cartilage integrity following oligo-fucoidan-based formula intervention were observed, highlighting its protective effects against cartilage degeneration and structural damage. Furthermore, the oligo-fucoidan-based formula modulated the p38 signaling pathway, along with downregulating cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, contributing to its beneficial effects. Our study provides valuable insights into targeted interventions for OA management and calls for further clinical investigations to validate these preclinical findings and to explore the translational potential of an oligo-fucoidan-based formula in human OA patients.

Bixa orellana ethyl acetate fraction and its isolated compound ellagic acid attenuate the progression of MIA-induced osteoarthritis in rat knees.

Osteoarthritis (OA) is a pathology that is characterized by progressive erosion of articular cartilage. In this context, medicinal plants have become relevant tools regarding their potential role in the prevention and treatment of OA, being safe and effective. The aim of this work was investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of OA induced by monosodium iodoacetate (MIA) in rats. The plant material was extracted via maceration with 70 % hydroalcoholic solvent (BoHE). The ethyl acetate (BoEA) fraction was by solvents in increasing order of polarity. The ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-DAD) and analytical curve. The OA was induced using MIA in the right knee at the knee joint. Doses of BoEA and ElAc were administered daily (every 24 h, orally) at concentrations of 50, 100 and 50 mg/kg, respectively, for 28 days after induced OA. We evaluated the animals through clinical and radiological examinations every 7 days and, on the 29th day, the animals were euthanized, the joints being removed for histopathological analysis and the serum for cytokine analysis. BoEA and ElAc compounds reduced inflammation and nociception in OA and were as effective as indomethacin in clinical parameters of joint discomfort and allodynia in rats, in addition to showing improvements in radiological and histopathological images, acting on the progress of cartilage deterioration, proving properties related to anti-inflammatory and analgesic processes, being important allies for new therapeutic interventions for the treatment of OA.

How well does XAD resin extraction recover halogenated disinfection byproducts for comprehensive identification and toxicity testing?

Halogenated disinfection byproducts (DBPs) are an unintended consequence of drinking water disinfection, and can have significant toxicity. XAD resins are commonly used to extract and enrich trace levels of DBPs for comprehensive, nontarget identification of DBPs and also for in vitro toxicity studies. However, XAD resin recoveries for complete classes of halogenated DBPs have not been evaluated, particularly for low, environmentally relevant levels (ng/L to low µg/L). Thus, it is not known whether levels of DBPs or the toxicity of drinking water might be underestimated. In this study, DAX-8/XAD-2 layered resins were evaluated, considering both adsorption and elution from the resins, for extracting 66 DBPs from water. Results demonstrate that among the 7 classes of DBPs investigated, trihalomethanes (THMs), including iodo-THMs, were the most efficiently adsorbed, with recovery of most THMs ranging from 50%-96%, followed by halonitromethanes (40%-90%). The adsorption ability of XAD resins for haloacetonitriles, haloacetamides, and haloacetaldehydes was highly dependent on the individual species. The adsorption capacity of XAD resins for haloacetic acids was lower (5%-48%), even after adjusting to pH 1 before extraction. Recovery efficiency for most DBPs was comparable with their adsorption, as most were eluted effectively from XAD resins by ethyl acetate. DBP polarity and molecular weight were the two most important factors that determine their recovery. Recovery of trichloromethane, iodoacetic acid, chloro- and iodo-acetonitrile, and chloroacetamide were among the lowest, which could lead to underestimation of toxicity, particularly for iodoacetic acid and iodo-acetonitrile, which are highly toxic.

Studies of the Antitumor Activity of Iodacetate in the Liposomal Form.

Metabolic reprogramming has become the new hallmark of cancer. Carbohydrate metabolism is a key component of metabolic transformations in tumors. To date, many therapeutic agents have been identified that target proteins and enzymes involved in glucose transport and metabolism, with promising results in cell culture studies and animal tumor models. In our studies, we found that the most promising among them is the glycolysis inhibitor iodoacetate. The study of this agent showed that iodoacetate in liposomal form has the best performance. With a course introduction, its antimetastatic and antitumor activity reached significant indices of growth inhibition. At the same time, liposomes with iodoacetate had an almost completely safe toxicological profile compared to the independent form and, as a result, have great potential in polychemotherapy.

Response of Bovine Cumulus-Oocytes Complexes to Energy Pathway Inhibition during In Vitro Maturation.

Glucose or fatty acids (FAs) metabolisms may alter the ovarian follicle environment and thus determine oocyte and the nascent embryo quality. The aim of the experiment was to investigate the effect of selective inhibition of glucose (iodoacetate + DHEA) or FA (etomoxir) metabolism on in vitro maturation (IVM) of bovine COCs (cumulus-oocyte complexes) to investigate oocyte's development, quality, and energy metabolism. After in vitro fertilization, embryos were cultured to the blastocyst stage. Lipid droplets, metabolome, and lipidome were analyzed in oocytes and cumulus cells. mRNA expression of the selected genes was measured in the cumulus cells. ATP and glutathione relative levels were measured in oocytes. Changes in FA content in the maturation medium were evaluated by mass spectrometry. Our results indicate that only glucose metabolism is substantial to the oocyte during IVM since only glucose inhibition decreased embryo culture efficiency. The most noteworthy differences in the reaction to the applied inhibition systems were observed in cumulus cells. The upregulation of ketone body metabolism in the cumulus cells of the glucose inhibition group suggest possibly failed attempts of cells to switch into lipid consumption. On the contrary, etomoxir treatment of the oocytes did not affect embryo development, probably due to undisturbed metabolism in cumulus cells. Therefore, we suggest that the energy pathways analyzed in this experiment are not interchangeable alternatives in bovine COCs.

Metformin Attenuates Monosodium-Iodoacetate-Induced Osteoarthritis via Regulation of Pain Mediators and the Autophagy-Lysosomal Pathway.

Osteoarthritis (OA) is the most common degenerative arthritis associated with pain and cartilage destruction in the elderly; it is known to be involved in inflammation as well. A drug called celecoxib is commonly used in patients with osteoarthritis to control pain. Metformin is used to treat type 2 diabetes but also exhibits regulation of the autophagy pathway. The purpose of this study is to investigate whether metformin can treat monosodium iodoacetate (MIA)-induced OA in rats. Metformin was administered orally every day to rats with OA. Paw-withdrawal latency and threshold were used to assess pain severity. Cartilage damage and pain mediators in dorsal root ganglia were evaluated by histological analysis and a scoring system. Relative mRNA expression was measured by real-time PCR. Metformin reduced the progression of experimental OA and showed both antinociceptive properties and cartilage protection. The combined administration of metformin and celecoxib controlled cartilage damage more effectively than metformin alone. In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3Ⅱb, p62, and LAMP1 expression, and induced an autophagy-lysosome fusion phenotype. We investigated if metformin treatment reduces cartilage damage and inflammatory cell death of chondrocytes. The results suggest the potential for the therapeutic use of metformin in OA patients based on its ability to suppress pain and protect cartilage.

Protective effects of Phlomis umbrosa extract on a monosodium iodoacetate-induced osteoarthritis model and prediction of molecular mechanisms using transcriptomics.

BACKGROUND: Phlomis umbrosa Turczaninow root has been traditionally used to treat fractures, rheumatoid arthritis, and arthralgia. However, the effects and mechanisms of P. umbrosa on osteoarthritis (OA) remain poorly understood and a functional genomic approach has not been investigated. AIM: The purpose of this study was to investigate the effects and mechanisms of P. umbrosa extract (PUE) on OA using transcriptomic analysis. METHODS: We performed joint diameter measurements, micro computed tomography, and histopathological analysis of monosodium iodoacetate (MIA)-induced OA rats treated with PUE (200 mg/kg) for 3 weeks. Gene expression profiling in articular cartilage tissue was then performed using RNA sequencing (RNA-seq) followed by signaling pathway analysis of regulatory genes. RESULTS: PUE treatment improved OA based on decreased joint diameter, increased joint morphological parameters, and histopathological features. Many genes involved in multiple signal transduction pathway and collagen activation in OA were differentially regulated by PUE. These included genes related to Wnt/ß-catenin, OA pathway, and sonic hedgehog signaling activity. Furthermore, PUE treatment downregulated cartilage damage factors (MMP-9, MMP-13, ADAMTs4, and ADMATs5) and upregulated chondrogenesis (COL2A1 and SOX-9) by regulating the transcription factors SOX-9, Ctnnb1, and Epas1. CONCLUSION: Based on the results of gene expression profiling, this study highlighted the molecular mechanisms underlying the effects of PUE in MIA-induced OA rats. The findings provide novel insight into the mechanisms by which PUE treatment-induced gene expression changes may influence OA disease progression. Taken together, the results suggest that PUE may be used as a source of therapeutic agents for OA.

Antarctic Krill Oil Ameliorates Monosodium Iodoacetate-Induced Irregularities in Articular Cartilage and Inflammatory Response in the Rat Models of Osteoarthritis.

The aim of this study was to examine the effects of Antarctic krill oil (FJH-KO) in a rat model of monosodium iodoacetate (MIA) induced osteoarthritis. The effect of FJH-KO on the development and severity of MIA-induced osteoarthritis was assessed using hematoxylin and eosin (H&E) staining and micro-CT. The expression of PGE2, pro-inflammatory cytokines (IL-1ß, TNF-α), and arthritics related genes in osteoarthritic rats in response to FJH-KO supplementation was investigated using real time PCR. FJH-KO supplementation in the arthritic rat model reduced tissue damage, cartilage degeneration, and reduced the MIA-induced irregularities in articular cartilage surface. Serum PGE2, IL-1ß, IL-6, and TNF-α levels were higher in MIA treated animals, but these levels decreased upon FJH-KO supplementation. When FJH-KO was provided at a dose of 150 mg/kg b.w to MIA-treated animals, it significantly increased the mRNA expression of anabolic factors. The mRNA expression of catabolic factors was significantly decreased MIA-treated animals that were provided FJH-KO at a dose of 100 and 150 mg/kg b.w. Moreover, the mRNA expression of inflammatory mediators was significantly decreased MIA-treated animals supplemented with FJH-KO. These results suggest supplementation with FJH-KO ameliorates the irregularities in articular cartilage surface and improves the inflammatory response in the osteoarthritis. Thus, FJH-KO could serve as a potential therapeutic agent for osteoarthritis treatment.

Daphne mucronata enhances cell proliferation and protects human adipose stem cells against monosodium iodoacetate induced oxidative stress in vitro.

Mesenchymal stem cells (MSCs) are being used to treat many diseases as they exhibit great regenerative potential. However, MSC's transplantation sometimes does not yield the maximum regenerative outcome as they are unable to survive in inflammatory conditions. Several approaches including preconditioning are used to improve the survival rate of mesenchymal stem cells. One such recently reported approach is preconditioning MSCs with plant extracts. The present study was designed to evaluate the effect of Daphne mucronata extract on stressed human adipose-derived mesenchymal stem cells (hADMSCs). Isolated hADMSCs were preconditioned with different concentrations of Daphne muconata extract and the protective, proliferative, antioxidant and anti-inflammatory effect was assessed through various assays and expression analysis of inflammatory markers regulated through NF-κB pathway. Results suggest that preconditioning hADMSCs with Daphne mucronata increased the cell viability, proliferative and protective potential of hADMSCs with a concomitant reduction in LDH, ROS and elevation in SOD activity. Moreover, both the ELISA and gene expression analysis demonstrated down regulations of inflammatory markers (IL1-ß, TNF-α, p65, p50, MMP13) in Daphne mucronata preconditioned hADMSCs as compared to stress. This is the first study to report the use of MIA induced oxidative stress against hADMSC's and effect of Daphne mucronata on stressed hADMSCs. Results of these studies provided evidence that Daphne mucronata protects the hADMSCs during stress conditions by down regulating the inflammatory markers and hence increase the viability and proliferative potential of hADMSCs that is crucial for transplantation purposes.

Manjarix attenuated pain and joint swelling in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

High bone turnover state under osteoporotic changes induces pain-like behaviors in mild osteoarthritis model mice.

INTRODUCTION: Our previous studies demonstrated that a high bone turnover state under osteoporotic changes decreased the threshold of skeletal pain. Recent studies reported that the incidence of joint pain due to osteoarthritis (OA) in postmenopausal women was higher than that in males even with the same radiographic OA grade. The aim of this study was to evaluate whether a high bone turnover state affects the induction of pain-like behaviors in mild OA model mice. MATERIALS AND METHODS: We established mild OA model mice with accompanying osteoporotic changes by monosodium iodoacetate injection after ovariectomy. We assessed pain-like behaviors by von Frey test and paw-flick test; histological changes in OA joints; the expression of Runx2, Osterix, Osteocalcin, and Rankl; bone micro-architecture by µCT and measured serum tartrate-resistant acid-phosphatase 5b levels in the model mice. RESULTS: Pain-like behaviors in mice with OA and osteoporotic changes were significantly increased in comparison with those in OA mice without osteoporotic changes. The severity of histological OA changes did not differ significantly between the OA mice with and without osteoporotic changes. Bisphosphonate significantly improved pain-like behaviors accompanied with improvement in the high bone turnover state in the OA mice with osteoporosis, while it had no significant effect on pain-like behaviors in the OA mice without osteoporosis. In addition, the improvement was maintained for more than 4 weeks even after the discontinuation of bisphosphonate treatment. CONCLUSION: These results indicated that a high bone turnover state under osteoporotic changes could affect the induction of pain-like behaviors in mild OA model mice.

In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model.

Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.

Quantitation of Gait and Stance Alterations Due to Monosodium Iodoacetate-induced Knee Osteoarthritis in Yucatan Swine.

Knee osteoarthritis is one of the most common causes of chronic pain worldwide, and several animal models have been developed to investigate disease mechanisms and treatments to combat associated morbidities. Here we describe a novel method for assessment of locomotor pain behavior in Yucatan swine. We used monosodium iodoacetate (MIA) to induce osteoarthritis in the hindlimb knee, and then conducted live observation, quantitative gait analysis, and quantitative weight-bearing stance analysis. We used these methods to test the hypothesis that locomotor pain behaviors after osteoarthritis induction would be detected by multiparameter quantitation for at least 12 wk in a novel large animal model of osteoarthritis. MIA-induced knee osteoarthritis produced lameness quantifiable by all measurement techniques, with onset at 2 to 4 wk and persistence until the conclusion of the study at 12 wk. Both live observation and gait analysis of kinetic parameters identified mild and moderate osteoarthritis phenotypes corresponding to a binary dose relationship. Quantitative stance analysis demonstrated the greatest sensitivity, discriminating between mild osteoarthritis states induced by 1.2 and 4.0 mg MIA, with stability of expression for as long as 12 wk. The multiparameter quantitation used in our study allowed rejection of the null hypothesis. This large animal model of quantitative locomotor pain resulting from MIA-induced osteoarthritis may support the assessment of new analgesic strategies for human knee osteoarthritis.

FlexPro MD®, a Combination of Krill Oil, Astaxanthin and Hyaluronic Acid, Reduces Pain Behavior and Inhibits Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD® (a mixture of krill oil, astaxanthin, and hyaluronic acid; FP-MD) in a rat model of OA induced by monosodium iodoacetate (MIA). FP-MD significantly ameliorated joint pain and decreased the severity of articular cartilage destruction in rats that received oral supplementation for 7 days prior to MIA administration and for 21 days thereafter. Furthermore, FP-MD treatment significantly reduced serum levels of the articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptide of type II collagen (CTX-II), and the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), as well as mRNA expression levels of inflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, in the knee joint tissue. Our findings suggest that FP-MD is a promising dietary supplement for reducing pain, minimizing cartilage damage, and improving functional status in OA, without the disadvantages of previous dietary supplements and medicinal agents, including multiple adverse effects.

Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats.

BACKGROUND: Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 µL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1ß, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1ß, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1ß, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1ß, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION: DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1ß, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.

Chondroprotective and anti-inflammatory effects of amurensin H by regulating TLR4/Syk/NF-κB signals.

The low-grade, chronic inflammation initiated by TLR4-triggered innate immune responses has a central role on early osteoarthritis. Amurensin H is a resveratrol dimer with anti-inflammatory and anti-apoptotic effects, while its effects on TLR-4 signals to inhibit osteoarthritis are still unclear. In the present study, treatment with amurensin H for 2 weeks in monosodium iodoacetate-induced mice significantly slows down cartilage degeneration and inflammation using macroscopic evaluation, haematoxylin and eosin (HE) staining and micro-magnetic resonance imaging. In IL-1ß-stimulated rat chondrocytes, amurensin H suppresses the production of inflammatory mediators including nitric oxide, IL-6, IL-17, PGE2 and TNF-α using Greiss and ELISA assay. Amurensin H inhibits matrix degradation via decreasing levels of MMP-9 and MMP-13 using Western blot assay, promotes synthesis of type II collagen and glycosaminoglycan using immunostaining and safranin O staining, respectively. Amurensin H inhibits intracellular and mitochondrial reactive oxygen species (ROS) generation, and mitochondrial membrane depolarization using DCFH-DA, MitoSOX Red and JC-1 assay as well. IL-1ß stimulates TLR4 activation and Syk phosphorylation in chondrocytes, while amurensin H inhibits TLR4/Syk signals and downstream p65 phosphorylation and translocation in a time and dose-dependent manner. Together, these results suggest that amurensin H exerts chondroprotective effects by attenuating oxidative stress, inflammation and matrix degradation via the TLR4/Syk/NF-κB pathway.

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)

Effect of Alpinia oxyphylla extract in vitro and in a monosodium iodoacetate-induced osteoarthritis rat model.

BACKGROUND: Osteoarthritis (OA) affects the articular cartilage and subchondral bone of synovial joints and induces proinflammatory and anti-inflammatory pathway dysregulation, leading to pain. This study evaluated the anti-inflammatory and antiosteoarthritis effects of Alpinia oxyphylla extract (AOE) in vitro and in vivo. METHODS: The anti-inflammatory effect of AOE was evaluated in vitro in lipopolysaccharide (LPS)-treated RAW264.7 cells. The antiosteoarthritis effect of AOE was investigated in a monosodium iodoacetate (MIA)-induced rat model of OA. Rats were orally administered AOE (150 mg/kg or 300 mg/kg) or the positive control drug indomethacin (1 mg/kg) 3 days before MIA injection and once daily for 21 days thereafter. RESULTS: AOE significantly decreased the production of nitric oxide (NO, 68.2%), prostaglandin E2 (PGE2, 92.8%), interleukin-1ß (IL-1ß, 77.2%), interleukin-6 (IL-6, 39.9%), and tumor necrosis factor-alpha (TNF-α, 20.7%) and the activation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in LPS-treated RAW264.7 cells at a dose of 100 µg/ml. In addition, AOE attenuated joint pain, suppressed proinflammatory cytokine and mediator production and inhibited cartilage degradation in the MIA-induced rat OA model. CONCLUSION: These results demonstrate that AOE exerts potent anti-inflammatory effects and may be a useful therapeutic candidate against OA.

Does cartilage ERα overexpression correlate with osteoarthritic chondrosenescence? Indications from Labisia pumila OA mitigation.

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.

Evaluation iontophoretic delivery of a cationic ketoprofen prodrug for treating nociceptive symptoms in monosodium iodoacetate induced osteoarthritic rat model.

Topical nonsteroidal anti-inflammatory drugs have been used in treatment of osteoarthritis but their efficacy is marginal. One major reason is because of limited drug direct penetration to affected joint and muscle tissues from the topical application. The main purpose of this study was to evaluate a new topical treatment through enhancing the direct drug penetration to local muscle and joint tissues for improving topical treatment of osteoarthritis. A cationic prodrug, ketoprofen choline chloride (KCC) was synthesized for iontophoretic topical delivery. Anodal iontophoretic delivery of KCC and cathodal iontophoretic delivery of ketoprofen to the knee of live hairless rats were evaluated and the drug concentrations in the joint and muscle tissues over the time were determined. In addition, a knee osteoarthritis rat model was induced with intra-articular injection of monosodium iodoacetate solution. Anodal iontophoretic delivery of KCC, cathodal iontophoretic delivery of ketoprofen, or anodal iontophoretic delivery of sodium chloride were applied to the affected knee joint of each rat group, respectively. Knee joint pain was evaluated through a hind paw weight bearing study and knee joint inflammation was evaluated through measuring of the knee diameter. Iontophoretic delivery of KCC showed much higher drug concentration in the knee joint and muscle tissues, compared to iontophoretic delivery of ketoprofen. Treatment of rat knee joint with anodal iontophoresis of KCC also showed significant pain relief and knee inflammation reduction comparing to the control group, while treatment results from cathodal iontophoresis of ketoprofen were mostly not significantly different from the control group.