In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives.

Abstract

The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient's non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase - 2, pro-inflammatory cytokines like Tumour Necrosis Factor - α, Interleukin - 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase-2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of the test compounds.