Title:MG17, A Novel Triazole Derivative Abrogated Neuroinflammation and Related Neurodegenerative Symptoms in Rodents
Volume: 11
Author(s): Gangadhar Matharasala, Ganesh Samala and Yogeeswari Perumal*
Affiliation:
- Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Telangana,India
Keywords:
Neuroinflammation, Pro-inflammatory cytokines, Streptozotocin, Diabetic peripheral neuropathy, real time polymerase
chain reaction.
Abstract: 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.
