Haider Faleh Al-Saedi - College of Pharmacy, University of Al-Ameed, Karbala, Iraq
Hussein A. Ghanimi - College of Nursing, University of Al-Ameed, Karbala, Iraq
Seyedeh Mahdieh Khoshnazar - Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Mohammad B. Ghayour - Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
Arash Abdolmaleki - Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran

Objective(s): Celastrol is an herbal compound with neuroprotective properties. Our research aimed to assess the neuroprotective properties of celastrol on sciatic nerve transection in rats.Materials and Methods: The rats’ left sciatic nerve was cut and sutured directly. The animals were then given ۱ or ۲ mg/kg celastrol intraperitoneally for two weeks. The sensory and locomotor behaviors of the animals were then evaluated for ۱۶ weeks. Immunohistochemistry, ELISA, and real-time PCR were also utilized to evaluate macrophage polarization, cytokine secretion, and neurotrophin expression in injured nerves. Results: Results showed that both doses of celastrol significantly accelerated nerve regeneration and improved sensorimotor functional recovery when compared with controls. Nevertheless, administration of ۲ mg/kg of celastrol significantly outperforms treatment with a dose of ۱ mg/kg. Celastrol treatment-induced M۲ polarization in macrophages decreased proinflammatory cytokines at the injury site. It also increased the expression of BDNF mRNA.Conclusion: These findings suggest that a two-week treatment with celastrol had neuroprotective effects in a rat sciatic nerve transection model, most likely by inducing macrophage M۲ polarization and anti-inflammatory effects.

Celastrol, Cytokine, Inflammation, Macrophage, Sciatic nerve