benzofurans has been researched along with Osteoarthritis* in 9 studies
1 review(s) available for benzofurans and Osteoarthritis
1 trial(s) available for benzofurans and Osteoarthritis
8 other study(ies) available for benzofurans and Osteoarthritis
| Article | Year |
|---|---|
Development of a New Benzofuran-Pyrazole-Pyridine-Based Molecule for the Management of Osteoarthritis.
Osteoarthritis is a substantial burden for patients with the disease. The known medications for the disease target the mitigation of the disease's symptoms. So, drug development for the management of osteoarthritis represents an important challenge in the medical field. This work is based on the development of a new benzofuran-pyrazole-pyridine-based compound Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Humans; Osteoarthritis; Pyrazoles; Pyridines; Rats | 2023 |
DL-3-N-Butylphthalide Promotes Cartilage Extracellular Matrix Synthesis and Inhibits Osteoarthritis Development by Regulating FoxO3a.
Osteoarthritis (OA) has been reported as a progressive disease in the elderly, primarily characterized by degenerated articular cartilage. There has been no satisfactory drug for the treatment of OA. DL-3-n-butylphthalide (NBP), a small molecule compound extracted from celery seeds, may have antiapoptotic, antioxidant, and anti-inflammatory activities in numerous studies. However, the effects of NBP on OA and its mechanisms have been rarely reported. In this study, the effect of NBP on OA in vitro and in vivo and its possible mechanism were investigated. The results showed that NBP injection into the knee joint inhibited osteoarthritis development in a rat model of osteoarthritis induced by DMM+ACLT. NBP could increase the expressions of extracellular matrix-related components (such as type II collagen, aggrecan, proteoglycan 4, and SRY-box 9) in human osteoarthritic chondrocytes and cartilage explants. Moreover, NBP promoted the expressions of SOD and CAT. NBP upregulated the expression of FoxO3a by inhibiting the PI3K/AKT pathway, which subsequently inhibited the apoptosis of human OA chondrocytes. In conclusion, NBP promotes cartilage extracellular matrix synthesis and inhibits osteoarthritis development and the underlying mechanism related to the activation of FoxO3a. Topics: Aged; Animals; Benzofurans; Cartilage, Articular; Chondrocytes; Extracellular Matrix; Forkhead Box Protein O3; Humans; Osteoarthritis; Phosphatidylinositol 3-Kinases; Rats | 2022 |
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-1β-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-1β 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. Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Chondrocytes; Disease Models, Animal; Disease Progression; Extracellular Matrix; Inflammation Mediators; Interleukin-1beta; Iodoacetates; Mice; Models, Biological; NF-kappa B; Osteoarthritis; Oxidative Stress; Phosphorylation; Protective Agents; Protein Transport; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Stilbenes; Syk Kinase; Toll-Like Receptor 4; Transcription Factor RelA | 2020 |
MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis.
Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences. Topics: Animals; Benzofurans; Cells, Cultured; Chondrocytes; Coumarins; Hydrogen-Ion Concentration; Matrix Metalloproteinase 13; Mice; Mice, Inbred C57BL; Osteoarthritis; Theranostic Nanomedicine | 2020 |
Protective effects of psoralidin on IL‑1β‑induced chondrocyte apoptosis.
Chondrocyte apoptosis serves a key role in the pathogenesis of osteoarthritis. The present study aimed to investigate the protective effects of psoralidin on interleukin (IL)‑1β‑induced chondrocyte apoptosis and explore the underlying mechanisms. Chondrocytes were isolated from the articular cartilage of Sprague‑Dawley rats and were treated with 10 ng/ml IL‑1β and various doses of psoralidin (5, 10 or 15 µM). The ratio of apoptosis was measured by Annexin V/propidium iodide double‑labeling fluorescence‑activated cell sorting (FACS) analysis. Caspase‑3 and ‑9 activity was determined using a quantitative colorimetric assay. Intracellular levels of reactive oxygen species (ROS) were assessed using a dichlorofluorescein diacetate‑labeling FACS analysis, and the release of nitric oxide (NO) was measured using the Griess reaction method. In addition, protein expression levels were detected by western blotting. The results of the present study demonstrated that psoralidin may reduce IL‑1β‑induced chondrocyte apoptosis. Psoralidin pretreatment also reversed the inhibitory effects of IL‑1β on B‑cell lymphoma 2 (Bcl‑2) expression, and decreased the IL‑1β‑induced expression of Bcl‑2‑associated X protein, matrix metalloproteinase (MMP)‑1 and MMP‑13. Furthermore, psoralidin decreased IL‑1β‑induced caspase‑3 and ‑9 activity, NO release, ROS production and nuclear factor (NF)‑κB nuclear translocation. In addition, the NF‑κB inhibitor pyrriolidine‑dithiocarbamate exerted similar effects to psoralidin, thus suggesting that IL‑1β induced proapoptotic effects in rat chondrocytes via an NF‑κB‑dependent pathway. Since psoralidin could protect chondrocytes from IL‑1β‑induced apoptosis and MMP expression, the present results suggested that psoralidin may be considered a drug candidate for the treatment of osteoarthritis. Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Benzofurans; Cells, Cultured; Chondrocytes; Coumarins; Estrogen Receptor Modulators; Interleukin-1beta; Osteoarthritis; Psoralea; Rats, Sprague-Dawley | 2018 |
Salvianolic acid B inhibits IL-1β-induced inflammatory cytokine production in human osteoarthritis chondrocytes and has a protective effect in a mouse osteoarthritis model.
Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment. Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cartilage; Chondrocytes; Cytokines; Disease Models, Animal; Humans; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 13; Menisci, Tibial; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide; Osteoarthritis; Phosphorylation; Signal Transduction | 2017 |
Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis.
A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 are zinc metalloproteases commonly referred to as aggrecanase-1 and aggrecanase-2, respectively. These enzymes are involved in the degradation of aggrecan, a key component of cartilage. Inhibitors of these enzymes could be potential osteoarthritis (OA) therapies. A series of hydantoin inhibitors of ADAMTS-4 and ADAMTS-5 were identified from a screening campaign and optimized through structure-based drug design to give hydantoin 13. Hydantoin 13 had excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14. The compound also produced efficacy in both a chemically induced and surgical model of OA in rats. Topics: ADAM Proteins; ADAMTS4 Protein; ADAMTS5 Protein; Animals; Benzofurans; Cells, Cultured; Crystallography, X-Ray; Hydantoins; Male; Menisci, Tibial; Microsomes; Models, Anatomic; Models, Molecular; Molecular Structure; Osteoarthritis; Procollagen N-Endopeptidase; Protease Inhibitors; Rats; Rats, Inbred Lew; Structure-Activity Relationship; Tibial Meniscus Injuries | 2014 |
Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.
Modification of alpha-biphenylsulfonamidocarboxylic acids led to potent and selective MMP-13 inhibitors. Compound 16 showed 100% oral bioavailability in rats and demonstrated >50% inhibition of bovine cartilage degradation at 10 ng/mL. Topics: Administration, Oral; Animals; Benzofurans; Collagenases; Drug Evaluation, Preclinical; Enzyme Inhibitors; Inhibitory Concentration 50; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; Models, Molecular; Molecular Structure; Osteoarthritis; Rats; Substrate Specificity | 2005 |