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.

Fu C ，Zhang X ，Lu Y ，Wang F ，Xu Z ，Liu S ，Zheng H ，Liu X ... -  《-》

Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome via the LRP1/AMPK mediated autophagy induction.

Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSP dose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSP could significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together, LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.

Qiu WQ ，Pan R ，Tang Y ，Zhou XG ，Wu JM ，Yu L ，Law BY ，Ai W ，Yu CL ，Qin DL ，Wu AG ... -  《-》

Salvianolic Acids for Injection alleviates cerebral ischemia/reperfusion injury by switching M1/M2 phenotypes and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia in vivo and in vitro.

Ma DC ，Zhang NN ，Zhang YN ，Chen HS ... -  《-》

Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

Li X ，Yao M ，Li L ，Ma H ，Sun Y ，Lu X ，Jing W ，Nie S ... -  《-》

URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion.

Su SH ，Wu YF ，Lin Q ，Wang DP ，Hai J ... -  《Journal of Neuroinflammation》