MG17, A Novel Triazole Derivative Abrogated Neuroinflammation and Related Neurodegenerative Symptoms in Rodents.

BACKGROUND AND

OBJECTIVE

The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators.

METHODS

We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin- induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats. Pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified with RT-qPCR studies and histopathology studies were performed taking tissue samples from MeHg induced neurodegeneration rats. The effect of MG17 was assessed on local and acute inflammation through carrageenan-induced rat paw edema model.

RESULTS

We observed the reduction in nociceptive responses in DPN rats. Pain threshold was reduced greater than 50% in various pain assessment modules. Upregulated pro-inflammatory cytokines which are thought to have a prominent role in neuroinflammation was controlled near to normal level quantified by RT-PCR studies. However, MG17 was able to regulate IL-6 and TNF-α but not IL-1β.

CONCLUSION

Our results clearly suggest the beneficial potential of compound MG17 through inhibition of pro-inflammatory cytokines upregulation. MG17 could be an intriguing therapeutic approach in diabetesrelated neuro-pathophysiological conditions.