Asperosaponin VI inhibits LPS-induced inflammatory response by activating PPAR-γ pathway in primary microglia

Abstract Microglia cells are the main mediators of neuroinflammation. Activation of microglia often aggravates the pathological process of various neurological diseases. Natural chemicals have unique advantages in inhibiting microglia-mediated neuroinflammation and improving neuronal function. Here, we examined the effects of asperosaponin VI (ASA VI) on LPS-activated primary microglia. Microglia were isolated from mice and pretreated with different doses of ASA VI, following lipopolysaccharide (LPS) administration. Activation and inflammatory response of microglia cells were evaluated by q-PCR, immunohistochemistry and ELISA. Signaling pathways were detected by western blotting. We found that the ASA VI inhibited the morphological expansion of microglia cells, decreased the expression and release of proinflammatory cytokines, and promoted the expression of antiinflammatory cytokines in a dose-dependent manner. ASA VI also activated PPAR-γ signaling pathway in LPS-treated microglia. The anti-inflammatory effects of ASA VI in microglia were blocked by treating PPAR-γ antagonist (GW9662). These results showed that ASA VI promote the transition of microglia cells from proinflammatory to anti-inflammatory by regulating PPAR-γ pathway.