Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
Abstract Background: Morinda officinalis oligosaccharides (MOOs) is a traditional Chinese medicine extracted from plant Morinda officinalis roots. It has been used to treat mild and moderate depressive episodes. In the present study, we investigated whether MOOs can ameliorate depressive-like behaviors in post-stroke depression (PSD) rats and further discussed its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation.Methods: Behaviors tests were performed to evaluate the effect of MOOs on depressive-like behaviors in PSD rats. The effects of MOOs on the expression of IL-18, IL-1β and nucleotide-binding domain leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS)+adenosine triphosphate (ATP) stimulated BV2 cells by reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence and Western blot analysis. Adeno-associated virus (AAV) were injected into hippocampus to downregulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence.Results: MOOs can alleviate depressive-like behaviors in PSD rats. PSD rats showed increased expression of IL-18, IL-1β and NLRP3 inflammasome in the ischemic hippocampus, while MOOs compromised the elevation. NLRP3 downregulation ameliorated depressive-like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 is mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL-18, IL-1β and NLRP3 inflammasome in LPS+ ATP treated BV2 cells. We further showed that modulation of NLRP3 inflammasome by MOOs was associated with IκB/NF‐κB p65 signaling pathway.Conclusion: Overall, our study revealed the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD.