Anti-inflammatory property and COX-2 inhibitory activity of 28-Norolean-12-ENE-3,17-Diol isolated from calotropis procera: in vitro demonstration and in silico modeling

Abstract

The immune system exerts its protective ability against extraneous agents by mounting a inflammatory response. This inflammatory response should be short lived, prolonged inflammatory response results in immune disorders like Septic shock, Rheumatoid arthritis, Crohn s disease etc. Such inflammatory diseases afflict millions of people across the world. Treatment of these disorders is largely based on suppressing or interrupting the synthesis or action of inflammatory mediators in the host s response to injury. Present day therapeutics in use against these disorders are small molecule inhibitors, mostly steroidal. More recently Non-steroidal Antiinflammatory drugs (NSAID) have been the drug of choice in treating inflammatory disorders by regulating the Cyclooyxgenase pathway, non specifically. Novel NSAIDs target specifically only the inducible form of Cyclooyxgenase found in immune response cells. But these ranges of therapies still have their short-comings, by way of undesirable side-effects. This thesis deals with the identification and characterization of molecules from plants, which can be used as immuno-suppressive / modulating agents. It is thought that this strategy will bring in new possibilities for the future management of inflammation-based diseases. Medicinal plants have been widely used for the treatment of diseases in traditional medicine. This knowledge base is made use of for identification of bio-active molecules from Calotropis procera. This plant is well documented in traditional medical practices and hence its activities have been studied in greater detail. The bioactivity-based screens used in this study involves measuring the suppressive effect on the proliferative response of lymphocytes using [3H] Thymidine and monitoring factors that play an important role in regulating inflammatory mechanisms such as pro-inflammatory and anti-inflammatory cytokines, inflammatory mediators etc with a view to postulate the possible mechanism by which the plant extract could reduce inflammatory and imm