phenanthrenes has been researched along with Osteoarthritis* in 7 studies
7 other study(ies) available for phenanthrenes and Osteoarthritis
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Strategy for osteoarthritis therapy: Improved the delivery of triptolide using liposome-loaded dissolving microneedle arrays.
Osteoarthritis (OA) is a chronic disease that seriously impairs people's physical function and quality of life. Triptolide (TP), as a promising anti-inflammatory drug for the treatment of OA, has limited clinical application due to its severe systemic toxicity, poor solubility and rapid elimination in the body. To extend its application prospect for OA treatment. We have developed a liposome-loaded dissolving microneedle (DMN) system, which can effectively deliver poorly water-soluble TP and improve OA symptoms. To incorporate TP into DMNs, triptolide liposome (TP-Lipo) with entrapment efficiency of 90.25% was prepared by ethanol injection. Subsequently, TP-Lipo was concentrated by ultrafiltration tube and mixed with hyaluronic acid solution to prepare DMNs, TP-Lipo-loaded DMNs (TP-Lipo@DMNs) showed sufficient mechanical and insertion properties to penetrate about 200 μm of rat skin. The drug distribution in vivo showed that TP-Lipo@DMNs had a slow-release effect compared with intra-articular injection. In vivo pharmacodynamic research showed that TP-Lipo@DMNs significantly reduced knee joint swelling and the level of inflammatory cytokines (TNF-α, IL-1β, IL-6). Micro-CT and histological evaluation showed that TP-Lipo@DMNs effectively reduced cartilage destruction and alleviated OA symptoms. These results support that TP@Lipo@DMNs may be a promising option for OA treatment. Topics: Administration, Cutaneous; Animals; Diterpenes; Drug Delivery Systems; Epoxy Compounds; Liposomes; Osteoarthritis; Phenanthrenes; Quality of Life; Rats | 2021 |
Cryptotanshinone interferes with chondrocyte apoptosis in osteoarthritis by inhibiting the expression of miR‑574‑5p.
Chondrocyte apoptosis is an important factor in the development and progression of osteoarthritis (OA). Cryptotanshinone (CTS) can inhibit chondrocyte apoptosis, but the specific mechanism remains unknown. The aim of the present study was to explore how CTS may affect chondrocyte apoptosis. Reverse transcription‑quantitative PCR and western blotting were used to validate microRNA (miR)‑574‑5p, YY1‑associated factor 2 (YAF2), Bcl‑2 and Bax expression levels. H&E, Safranin O and TUNEL staining assays were used to evaluate the apoptosis of arthritic chondrocytes Topics: Animals; Apoptosis; Cell Proliferation; Chondrocytes; Down-Regulation; Genes, bcl-2; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Muscle Proteins; Osteoarthritis; Phenanthrenes; Repressor Proteins | 2021 |
Triptolide prevents osteoarthritis via inhibiting hsa-miR-20b.
Triptolide has been widely reported to exhibit potential therapeutic value in multiple inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Although its safety and efficacy as an anti-inflammatory agent have been verified by many studies, the effect of triptolide on osteoarthritis (OA) was not clearly understood. In this study, we found that triptolide prevented OA development in a surgical destabilization of the medial meniscus (DMM) mouse model. In addition, triptolide inhibited both DMM-induced and LPS-induced expression of pro-inflammatory cytokines in the human monocytic cell line THP-1. Further mechanistic studies showed that the reduction of pro-inflammatory cytokines by triptolide was mediated by the upregulation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) and downregulation of caspase-1. Finally, we identified that hsa-miR-20b, a microRNA targeting the NLRP3 gene, was downregulated by triptolide. This study provides a novel insight into the effect on triptolide in preventing OA pathogenesis. Topics: Animals; Cell Line; Cytokines; Disease Models, Animal; Diterpenes; Down-Regulation; Epoxy Compounds; Humans; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Monocytes; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoarthritis; Phenanthrenes; THP-1 Cells; Up-Regulation | 2019 |
Cryptotanshinone protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.
Osteoarthritis (OA) is a common degenerative disease characterized by progressive erosion of articular cartilage, subchondral bone sclerosis and synovitis. Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza Bunge, has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of CTS on human OA chondrocytes and mice OA models. Human OA chondrocytes were pretreated with CTS (5, 10 and 20μM) for 2h and subsequently stimulated with IL-1β for 24h. Production of NO, PGE2, IL-6, TNF-α was evaluated by the Griess reaction and ELISA. The protein expression of COX-2, iNOs, MMP-3, MMP13, COX-2, ADAMTS-5, JNK, p-JNK, ERK, p-ERK, p38, p-p38, p-IKKα/β, p65, p-p65, IκB-α, and p-IκB-α was tested by Western blot. In vivo, the severity of OA was determined by histological analysis. We found that CTS significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-3, MMP-13, and ADAMTS-5. Furthermore, CTS in dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that CTS could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. In vivo, treatment of CTS prevented the destruction of cartilage and the thickening of subchondral bone in mice OA models. These results indicate that the therapeutic effect of CTS on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Our findings provide the evidence to develop CTS as a potential therapeutic agent f or patients with OA. Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Disease Progression; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Middle Aged; NF-kappa B; Nitric Oxide; Osteoarthritis; Phenanthrenes; Salvia miltiorrhiza; Signal Transduction; Tumor Necrosis Factor-alpha | 2017 |
Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes.
Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-stimulated macrophages (i.e., acute inflammation). They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6) and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis. Topics: Abietanes; Animals; Chemokine CCL5; Chemokines; Chondrocytes; Collagen Type II; Cytokines; Gene Expression Regulation; Humans; Interleukin-1beta; Macrophages; Mice; NF-kappa B; Nitric Oxide; Osteoarthritis; Phenanthrenes; RAW 264.7 Cells | 2016 |
Denbinobin upregulates miR-146a expression and attenuates IL-1β-induced upregulation of ICAM-1 and VCAM-1 expressions in osteoarthritis fibroblast-like synoviocytes.
Interleukin-1β (IL-1β) upregulates intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions in osteoarthritis fibroblast-like synoviocytes (OA-FLS) via nuclear factor (NF)-κB-mediated mechanism; enhancement of leukocyte infiltration and upregulation of proinflammatory mediators play a crucial role in OA pathophysiology. MicroRNA (miR)-146a suppresses inflammatory responses by inhibiting NF-κB activity and target gene expression, and epigenetic mechanisms are reportedly involved in miR expression regulation. Here, we aimed to verify the inhibition of ICAM-1/VCAM-1 expression in OA-FLS on denbinobin treatment and to determine whether this inhibition was due to the miR-146a-dependent pathway. We also assessed the epigenetic regulation caused by histone acetyltransferases involved in denbinobin action. Denbinobin attenuated the upregulation of IL-1β-induced ICAM-1/VCAM-1 expression and monocyte adhesion to OA-FLS. The mechanism underlying the inhibitory effects of denbinobin involved miR-146a induction, which in turn inhibited NF-κB signaling. This is because miR-146a inhibitor abrogated the inhibitory effects of denbinobin. Furthermore, histone acetyltransferase inhibitor attenuated the denbinobin-induced upregulation of miR-146a expression and inhibited the acetylation of NF-κB-binding sites located within the miR-146a promoter region. These data suggest that an epigenetic mechanism plays a crucial role in the upregulation of miR-146a expression in response to denbinobin treatment. Our overall findings suggest that denbinobin can be used as a potent anti-inflammatory agent.. Denbinobin inhibited IL-1β-induced ICAM-1/VCAM-1 expression and monocyte adhesion to OA-FLS. It was due to denbinobin increased miR-146a level, which in turn inhibited NF-κB signaling. Our overall findings suggest that denbinobin can be used as a potent anti-inflammatory agent. Topics: Aged; Anthraquinones; Binding Sites; Cell Adhesion; Epigenesis, Genetic; Fibroblasts; Gene Expression Regulation; HeLa Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; MicroRNAs; Microscopy, Fluorescence; Monocytes; NF-kappa B; Osteoarthritis; Patella; Phenanthrenes; Signal Transduction; Synovial Membrane; Synoviocytes; Vascular Cell Adhesion Molecule-1 | 2014 |
The CCL5/CCR5 axis promotes interleukin-6 production in human synovial fibroblasts.
CCL5 (RANTES) was originally identified as a product of activated T cells and plays a crucial role in the inflammatory response. This study was undertaken to investigate the intracellular signaling pathways involved in CCL5-induced interleukin-6 (IL-6) production in human synovial fibroblasts.. CCL5-mediated IL-6 expression was assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms of action of CCL5 in different signaling pathways were studied using Western blotting. Knockdown of CCR5 and protein kinase Cδ (PKCδ) protein was achieved by transfection of small interfering RNA (siRNA). Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the IL-6 promoter. Transient transfection was used to examine IL-6 and activator protein 1 (AP-1) activity.. Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of CCL5 and CCR5, and expression was higher than that in normal synovial fibroblasts. Stimulation of OASFs with CCL5 induced concentration- and time-dependent increases in IL-6 production. CCL5-mediated IL-6 production was attenuated by CCR5 monoclonal antibody, CCR5 inhibitor (Met-RANTES), and CCR5 siRNA. Pretreatment with a PKCδ inhibitor (rottlerin), a c-Src inhibitor (PP2), or an AP-1 inhibitor (tanshinone IIA) also blocked the potentiating action of CCL5. Treatment of OASFs with CCL5 increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the IL-6 promoter. CCL5-mediated AP-1 luciferase activity and c-Jun binding to the AP-1 element were inhibited by Met-RANTES, rottlerin, and PP2.. The present results suggest that the interaction between CCL5 and CCR5 increases IL-6 production in human synovial fibroblasts via the PKCδ/c-Src/c-Jun and AP-1 signaling pathways. Topics: Abietanes; Acetophenones; Benzopyrans; Cells, Cultured; Chemokine CCL5; CSK Tyrosine-Protein Kinase; Fibroblasts; Humans; Interleukin-6; Osteoarthritis; Phenanthrenes; Protein Kinase C-delta; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-jun; Pyrimidines; Receptors, CCR5; Signal Transduction; src-Family Kinases; Synovial Membrane; Transcription Factor AP-1 | 2010 |