The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after sin...The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered （15 mg/kg） once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and sub- chondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive sub- chondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pro- nounced after 12 weeks as compared to 8 weeks in both cases （i.e., post 1 and 2 weeks of iodoacetate injection）. Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chon- droprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.展开更多
Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen fo...Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.展开更多
Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatmen...Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatment,was evaluated for its impact on CRC proliferation and migration,alongside its underlying mechanisms,through both in vitro and in vivo analyses.The study employed MTT assay,colony formation,wound healing,transwell assays,flow cytometry,and Hoechst 33342 staining to assess cell proliferation,migration,and apoptosis.Additionally,proteome microarray assay and western blotting analyses were conducted to elucidate diacerein’s specific mechanism of action.Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo.Through high-throughput proteomics microarray and molecular docking studies,we identified that diacerein directly interacts with DCLK1.Mechanistically,the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed.Furthermore,diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets,including MCL-1,VEGF,and survivin,thereby inhibiting CRC progression in a mouse model,thereby inhibiting CRC progression in a mouse model.展开更多
目的评价双醋瑞因(止痛抗炎药)治疗骨关节炎的疗效及安全性。方法用多中心、开放试验设计,以服药前后病情改变作为疗效判断指标;372骨关节炎患者服用双醋瑞因每次1粒(50mg),每日2次,疗程12周。均通过visual analog scale(VAS)评分判断。...目的评价双醋瑞因(止痛抗炎药)治疗骨关节炎的疗效及安全性。方法用多中心、开放试验设计,以服药前后病情改变作为疗效判断指标;372骨关节炎患者服用双醋瑞因每次1粒(50mg),每日2次,疗程12周。均通过visual analog scale(VAS)评分判断。372例全部纳入安全性评价;而318例膝关节炎病例纳入疗效分析。结果与治疗前相比,318例膝骨关节炎患者的关节触痛、20米步行痛评分有明显改善(P<0.01);发生药物不良反应为6.72%(25/372),主要为轻、中度的胃肠道反应,未发生严重不良事件。结论双醋瑞因治疗骨关节炎安全有效。展开更多
基金University Grant Commission,New Delhi for the financial support in the form of Senior Research FellowshipDr.Reddy's Laboratories Ltd.(Hyderabad, India) for providing diacerein as gift sample
文摘The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered （15 mg/kg） once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and sub- chondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive sub- chondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pro- nounced after 12 weeks as compared to 8 weeks in both cases （i.e., post 1 and 2 weeks of iodoacetate injection）. Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chon- droprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.
文摘Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.
基金supported by the National Natural Science Foundation of China(Nos.82173856 and 82203322)the Natural Science Foundation of Zhejiang Province(Nos.LY21H300005 and LGF22H030014)+1 种基金Wenzhou Municipal Science and Technology Bureau(Nos.ZY2020025 and H20210009)the Science and Technology Innovation Activity Plan for College Students of Zhejiang Province(No.2019R413012)。
文摘Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatment,was evaluated for its impact on CRC proliferation and migration,alongside its underlying mechanisms,through both in vitro and in vivo analyses.The study employed MTT assay,colony formation,wound healing,transwell assays,flow cytometry,and Hoechst 33342 staining to assess cell proliferation,migration,and apoptosis.Additionally,proteome microarray assay and western blotting analyses were conducted to elucidate diacerein’s specific mechanism of action.Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo.Through high-throughput proteomics microarray and molecular docking studies,we identified that diacerein directly interacts with DCLK1.Mechanistically,the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed.Furthermore,diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets,including MCL-1,VEGF,and survivin,thereby inhibiting CRC progression in a mouse model,thereby inhibiting CRC progression in a mouse model.
文摘目的评价双醋瑞因(止痛抗炎药)治疗骨关节炎的疗效及安全性。方法用多中心、开放试验设计,以服药前后病情改变作为疗效判断指标;372骨关节炎患者服用双醋瑞因每次1粒(50mg),每日2次,疗程12周。均通过visual analog scale(VAS)评分判断。372例全部纳入安全性评价;而318例膝关节炎病例纳入疗效分析。结果与治疗前相比,318例膝骨关节炎患者的关节触痛、20米步行痛评分有明显改善(P<0.01);发生药物不良反应为6.72%(25/372),主要为轻、中度的胃肠道反应,未发生严重不良事件。结论双醋瑞因治疗骨关节炎安全有效。
