Anti-inflammatory and Anti-nociceptive Activities of 7β-(3-ethylcis-crotonoyloxy)-1α-(2- methylbutyryloxy)-3, 14-dehydro-Z notonipetranone (ECN) in Rodents

Abstract

Inflammation in localized area of the organ is associated with tissue damage that typically aims to keep defense of the host. Moreover, long term and continuous inflammation cause persistent illness. Several anti-inflammatory drugs are available in market involved with serious hazardous outcomes. As a result of these serious problems, novel anti-inflammatory agents with less adverse effects are much needed. Consequently, the contemporary research was carried out to explore the anti inflammatory and anti-nociceptive potentials of 7β-(3-ethylcis-crotonoyloxy)-1α-(2- methylbutyryloxy)-3, 14-dehydro-Z-notonipetranone (ECN) in inflammatory and neuropathic pain models of rodents. Newly isolated compound was distinguished by differentiation with spectral data spectroscopic analysis. In the early stages, ECN was confirmed for anti-inflammatory and anti-nociceptive potentials by carrying out carrageenan-triggered paw thickness and paw removal threshold. Thermal hyperalgesia was evaluated by hot plate model in mice. Furthermore, the anti inflammatory and anti-nociceptive potential of ECN was then confirmed in complete Freund adjuvant (CFA) triggered inflammation in rodents. So for the purpose to explore the ECN effect on neuropathic pain, partial sciatic nerve ligation (PSNL) model was carried out. The results obtained demonstrated that ECN significantly inhibited inflammation and pain in all the models at 10 mg/kg. Moreover, the anti inflammatory and anti-nociceptive activities of ECN were further confirmed by evaluating inflammatory mediators and anti-oxidant enzymes in CFA-induced paw tissue and PSNL induced hippocampus, prefrontal cortex, lumbar spinal cord and sciatic nerve tissue. The data surely indicated the noticeable decrement in the inflammatory mediator level while enhancing anti-oxidant enzymes. ECN also inhibited DNA damage in sciatic, spinal and paw neuronal cells as analyzed by comet assay. Soft tissue examination of inflamed paw by x-ray imaging and hippocampus, sciatic nerve and spinal cord tissue were done through H&E staining. Side effects profile of drug was gathered by monitoring kidney and liver function tests. Kodzeila’s screen and weight test were accomplished to see negative effect on motor activity. Pretreatment with ECN did not caused any hazardous effect on liver, muscles and kidney. These finding recommend that ECN exhibits anti-inflammatory and neuroprotective potentials. Thus, ECN might be potent alternative prospect for the cure of chronic inflammation and neuropathy. Key words: ECN, inflammation, neuropathic pain, DNA damage, anti-oxidant enzyme.