2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride inhibits microglial activation by suppression of nuclear factor-kappa B and mitogen-activated protein kinase signaling.

The activation of microglia is crucially associated with the neurodegeneration observed in many neuroinflammatory pathologies, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Therefore, the inhibition of microglial activation may alleviate certain neurodegenerative processes. We previously demonstrated the protective actions of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377), against glutamate-induced excitotoxicity and ischemic neuronal damage in in vivo rat brain study. The current investigation explored the possible mechanisms underlying the anti-inflammatory effects of this compound against lipopolysaccharide (LPS)-stimulated activation of cultured BV-2 microglial cells. The results showed that KHG26377 reduced the production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), reactive oxygen species (ROS), and nitric oxide (NO) in LPS-activated microglia. Furthermore, KHG26377 attenuated LPS-mediated increases in the protein expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR4), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). The compound also prevented the LPS-provoked translocation of the nuclear factor-kappa B (NF-κB) p65 subunit (NF-κB-p65) from the cytosol into the nucleus of BV-2 cells. These findings suggest that KHG26377 may find utility as a therapeutic agent that can be further developed for the management of various neuroinflammatory conditions.