The Cannabinoid Receptors Agonist, β-Amyrin, Modulates LPS/IFN-y Induced M1/M2 Microglia Imbalance

Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells. Cytotoxicity of β-Amyrin (3-100) μM on microglialcells was evaluated using the MTT assay. Also, the protective effect of various β-Amyrin (2-16 μM) concentrations with LPS/IFN-γ-induced mice microglial cells was studied. The concentrations of TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin- 1β), IL-6 (Interleukin-6) and PGE-2 (Prostaglandin E2) were evaluated using ELISA. Gene expressions of TNF-α, IL-1β, IL-6, COX-2 (Cyclooxygenase-2), iNOS and arginase-1 were also evaluated using the Real-Time PCR method. Nitrite oxide and urea were measured using biochemical methods. The studiedconcentrations of β-Amyrin had no significant effects on the viability of microglial cells. Interestingly, β-Amyrin concentration dependently and significantly increased the reduced cell proliferation concerning to LPS/IFN-γ exposu r e (p < 0.001). The concentrationsand expression l e vels of pro-inflammatory factors including TNF-α, IL-1β, IL-6, PGE-2, COX-2 were significantly re d uced after β-Amyrin treatment in LPS/IFN-γ-induced microglial cells (p < 0.05-0.001). β-Amyrin also d e creased the levels of nitric oxide, increased urea a nd down regulated the expression of nitric oxide synthesis while arginase-1 expression was enhanced (p < 0.001). The ratio of NO/urea and iNOS/Arg1 were also markedly increased in comparison to the LPS/IFN-g g r oup (p < 0.001). β-Amyrin reduces inflammation in microglial cells and can be used as a potential anti - inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple s clerosis, by affecting the inflammatory cytokine and d ifferentiation of microglia as resident CNS macrophag e s.