EFFECT OF NON-PSYCHOTROPIC CANNABIS SATIVA L. EXTRACT ON LPS-INDUCED MICROGLIAL RESPONSE

Recent studies proposed non-psychotropic Cannabis sativa L. and its major cannabinoid compounds as having a role in main pathogenic mechanisms involved in neuroinflammation. Inflammatory re- sponse in the brain provides the initial activation of microglial cells which induce the release of pro- inflammatory cytokines, such as IL-1 , IL-6 and TNF- , that act at different levels in the central nervous system (CNS). The purpose of this study was to investigate the CB2r and pro-inflammatory cytokines modulation in an in vitro model of microglia, in order to evaluate the effect of chemically standardized extract of C. sativa and its main constituents, namely cannabidiol (CBD), b-caryophil- lene (CAR) and apigenin (APG), on central neuroinflammation. Short term exposure to LPS significantly downregulated CB2r transcription and protein levels in BV- 2 cells. On the contrary, the expression of IL-1 , IL-6 and TNF- resulted markedly enhanced already at early time LPS stimulation. Pre-treatment of microglial cells with C. sativa extract, CBD, CAR and APG was able to upregulate CB2r protein levels, but only the extract attenuated pro-inflammatory cytokines expression induced by LPS. C. sativa phytocomplex was able to inhibit LPS-induced mi- croglia activation through regulation of pro-inflammatory cytokines and CBr. These results suggest a potential anti-inflammatory effect of the extract compared to its main constituents.