Evaluation of the chondroprotective effect of mutual prodrug of diacerein in monosodium iodoacetate-induced osteoarthritis in Wistar rats

We have reported synthesis and in vitro release studies of a gastro-sparing mutual prodrug of diacerein with the nutraceutical aminosugar; Dglucosamine as a promoiety. The results of preliminary pharmacological screening were promising which prompted us to evaluate its potential for long-term use in the safer management of osteoarthritis. This work reports the results of three-month extensive studies in monosodium iodoacetate- induced osteoarthritis in wistar rats. The prodrug significantly reduced knee diameter and serum alkaline phosphatase to the baseline levels on the 60th day of drug intervention maintaining both the effects even on the 90th day of drug intervention. In contrast, diacerein displayed no effect on the knee diameter till the 90th day of drug intervention while a decreasing effect on serum alkaline phosphatase levels was displayed on the 15th day of drug intervention but was not maintained till the end of the study. Pretreatment with diacerein for 90 days significantly decreased the mean serum glycosaminoglycan level to the baseline value to the extent of 84-92% while the prodrug's reducing effect was in the range of 74-94%. Histopathological findings of the cartilage were assessed by osteoarthritis grading score in which the prodrug displayed better chondroprotection than diacerein.