Salvianolic acid B exerts protective effects against Aβ-induced neuroinflammation through the inhibition of NLRP3 inflammasome activation and switching of M1/M2 polarization.

BACKGROUND: Salvianolic acid B (SalB) is a bioactive extract of Salvia miltiorrhiza with the ability to ameliorate amyloid beta (Aβ)-induced neuronal degeneration and neuroinflammation in Alzheimer's disease (AD). However, the underlying mechanisms of this action have not been elucidated. Herein, we aimed to investigate whether the neuroprotective effect of SalB is attributable to the modulation of microglial polarization and NLRP3 inflammasome-mediated neuroinflammation.

METHODS: Based on the TMT-labeled proteomics analysis, immunofluorescence, western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to investigate the effects of SalB on neuroinflammation in Aβ1-42-stimulated BV2 microglia cells.

RESULTS: At the proteomic level, a total of 6631 proteins were quantified, and of these, 104 were significantly influenced under Aβ1-42 treatment. The expression of 36 Aβ1-42-induced differentially expressed proteins were significantly recovered by SalB treatment (13 upregulated and 23 downregulated). NLRP3 was significantly recovered and was identified as one of the hub proteins. Consistent with the result of the proteomic analysis, western blot and qRT-PCR demonstrated that SalB reduced Aβ1-42-induced NLRP3 upregulation at both the protein and mRNA levels. In addition, SalB significantly blocked M1 microglia polarization, enhanced M2 microglial polarization, and inhibited the production of caspase-1 and interleukin-1β in BV2 microglia cells.

CONCLUSION: our study demonstrated, for the first time, that the anti-inflammatory effects of SalB were mediated by the regulation of NLRP3 activation and promotion of microglial M2 polarization, indicating the potential of SalB as a novel therapeutic candidate for AD.