Geniposide inhibits NLRP3 inflammasome activation via autophagy in BV-2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation.

The nod-like receptor protein 3 (NLRP3) inflammasome has a critical role in cerebral ischemia. Autophagy may cause microglial inflammatory response or stimulate microglial function. The evidences clarify a direct crosstalk between autophagy and NLRP3. Geniposide could protect neurons or PC-12 cells against cerebral ischemic injury. However, a detailed understanding of molecular mechanisms on geniposide is still unclear. This study aimed to evaluate whether geniposide could inhibit the expression and activation of NLRP3 inflammasome in BV-2 microglial cells following oxygen-glucose deprivation/reoxygenation (OGD/R) and assessed whether autophagy is involved in this process. We used OGD/R model in BV2 microglial cells in order to mimic the ischemic reperfusion injury. The NLRP3 shRNA and autophagy inhibitor (3-MA) were used to suppress NLRP3 inflammation activation and autophagy. The results demonstrated geniposide decreased cell death and the levels of NLRP3, ASC, cleaved- caspase-1 and IL-1β, whereas significantly increased the conversion of LC3 and Beclin-1 expression, decreased the expression of P62. Taken together, our results suggested that the effect of geniposide could be ascribed to the reduction of the level of inflammatory cytokines via inhibiting the activation and expression of NLRP3 inflammasome and increasing autophagic activity following OGD/R in BV-2 microglial cells. We provided a new understanding of geniposide in neuroprotection by activating autophagy and promoting anti-inflammation inhibiting NLRP3 inflammasome in microglial cells. It might be helpful for geniposide on effective therapeutic strategies in ischemic stroke.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.