Protective effects of hydro-ethanolic extract of Terminalia chebula on primary microglia cells and their polarization (M1/M2 balance)

Teminalia chebula (TC) has been traditionally used in the Iranian traditional medicine (ITM) and Ayurvedic medicine primarily for neurologic disorders and inflammation. Mainly, its fruits have been applied for CNS disorders. The effects of Terminalia chebula as herbal medicine with anti-inflammatory and anti-oxidant properties were aimed on lipopolysaccharide (LPS)-induced microglial inflammation. Cytotoxicity of TC extract (0-80) mu g/ml on microglial cells was evaluated using the MTT assay. Also, the protective effect of TC extract concentrations with specified amount of LPS-induced mice microglial cells was studied. The concentrations of TNF-alpha (Tumor Necrosis Factor-alpha), IL-1 beta (Interleukin-1 beta, IL-6 and PGE-2 (Prostaglandin-E2) were evaluated using ELISA. Gene expression of TNF-alpha, IL-1 beta, IL-6, COX-2 (Cyclooxygenase-2), iNOS and arginase-1 was also evaluated using the Real-Time PCR method. Nitrite oxide and urea were measured using biochemical methods. The studied concentrations of TC extract did not affect the viability of microglial cells but significantly protected the viability after treatment with LPS. The concentrations and expression levels of pro-inflammatory factors (TNF-alpha, IL-1 beta, IL-6, PGE-2, COX-2) were significantly decreased after TC extract treatment in LPS-induced microglial cells with dose dependent manner. The extract also significantly decreased the levels of nitric oxide, increased urea and down regulated the expression of nitric oxide synthesis while arginase-1 expression was enhanced. Our results suggest that TC extract reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system inflammatory diseases.