p53 contributes to quercetin-induced apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes

p53 contributes to quercetin-induced apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes.

In the present study, we sought to explore the mechanism of quercetin-induced apoptosis in rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). DNA fragmentation assay was used to detect quercetin-induced apoptosis in RAFLSs. The cleavages of caspase-3 and caspase-9 and the accumulation of cytosolic cytochrome C were measured by western blot in quercetin-treated RAFLSs. Mitochondrial membrane potential was tested by flow cytometry. Small interfering RNAs were used to knock down the expression of protein 53 (p53) and analyze the role of p53 in quercetin-induced apoptosis in RAFLSs. DNA fragmentation assay showed that quercetin dose-dependently elevated the apoptosis of RAFLSs, accompanying with enhanced caspase-3 and caspase-9 cleavages. Moreover, quercetin caused a concentration-dependent loss of mitochondrial membrane potential and cytochrome c release to cytosol and also decreased Bcl-2/Bax ratio, indicating that quercetin-induced apoptosis is through mitochondrial pathway. Quercetin also elevated p53 phosphorylation at ser15. Pretreatment with pifithrin-α, a p53 inhibitor, significantly diminished p53 phosphorylation at the concentration of 30 μM and abrogated quercetin-induced apoptosis in a dose-dependent manner. Quercetin-induced apoptosis was also significantly blocked by p53 silencing, further suggesting the involvement of p53 in quercetin-induced apoptosis in RAFLSs. Our study indicated that quercetin-induced apoptosis of RAFLSs is through mitochondrial pathway, in which p53 plays an important role.

Enhancement of anti arthritic effect of quercetin using thioglycolic acid-capped cadmium telluride quantum dots as nanocarrier in adjuvant induced arthritic Wistar rats.

In this present study, we investigated thio glycolic acid-capped cadmium telluride quantum dots (TGA-CdTe QDs) as nano carrier to study the antiarthritic activity of quercetin on adjuvant induced arthritic Wistar rats. The free radical scavenging activity of QDs-QE complex was evaluated by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide anion scavenging assays. Fifteen days after adjuvant induction, arthritic rats received QDs-QE complex orally at the dose of 0.2 and 0.4mg/kg daily for 3 weeks. Diclofenac sodium (DF) was used as a reference drug. Administration of QDs-QE complex showed a significant reduction in inflammation and improvement in cartilage regeneration. Treatment with QDs-QE complex significantly (P<0.05) reduced the expressions lipid peroxidation and showed significant (P<0.05) increase in activities of antioxidant enzymes such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) catalase (CAT) levels in paw tissue. C-reactive protein (CRP), rheumatoid factor (RF), red blood cells (RBC) and white blood cells (WBC) count and erythrocyte sedimentation rate (ESR) of experimental animals were also estimated. Histology of hind limb tissue in experimental groups confirmed the complete cartilage regeneration in arthritis induced rats treated with QDs-QE complex. Based on our findings, we suggest that the QDs act as nano carrier for the drugs used in the treatment of various degenerative diseases.