Corilagin attenuates morphine-induced BV2 microglial activation and inflammation via regulating TLR2-mediated endoplasmic reticulum stress.

Morphine-induced microglia activation and neuroinflammation have been considered as the contributors of morphine tolerance. Corilagin (Cori) has been reported to exhibit strong anti-inflammatory property. The present study aims to investigate whether and how Cori alleviates morphine-induced neuroinflammation and microglia activation. Mouse BV-2 cells were exposed to different concentrations of Cori (0.1, 1 and 10 μM) prior to morphine stimulation (200 μM). Minocycline (10 μM) acted as the positive control. Cell viability was determined by CCK-8 assay and trypan blue assay. The levels of inflammatory cytokines were determined using ELISA. IBA-1 level was examined via immunofluorescence. TLR2 expression level was examined by quantitative real-time PCR and western blot. The expression levels of corresponding proteins were measured by western blot. It was found that Cori was non-toxic to BV-2 cells but greatly inhibited morphine-induced IBA-1 expression, overproduction of pro-inflammatory cytokines, activation of NLRP3 inflammasome and endoplasmic reticulum stress (ERS), and upregulation of COX-2 and iNOS. TLR2 was negatively regulated by Cori, and could promote the activation of ERS. A high affinity between Cori and TLR2 protein was confirmed via Molecular docking investigation. Moreover, TLR2 overexpression or tunicamycin (TM), an agonist of ERS, partly abolished the inhibitory effects of Cori on morphine-induced alternations on neuroinflammation and microglial activation in BV-2 cells as above. In summary, our study suggested that Cori effectively alleviated morphine-induced neuroinflammation and microglia activation through inhibiting TLR2-mediated ERS in BV-2 cells, providing a novel potential drug to overcome morphine tolerance.