Santalum album extract exhibits neuroprotective effect against the TLR3-mediated neuroinflammatory response in human SH-SY5Y neuroblastoma cells

Phytother Res. 2021 Apr;35(4):1991-2004. doi: 10.1002/ptr.6942. Epub 2020 Nov 9.

Abstract

Neuroinflammation is an inflammatory response in the nervous system that is associated with various neurological diseases including Alzheimer's diseases and others. Many studies evaluated the anti-inflammatory potential of Santalum album (S. album) extract, but none of them analyzed its effects against neuroinflammatory response in vitro. In addition, the precise mechanism underlying the anti-inflammatory effect of the extract has not yet been elucidated. Therefore, in this study, we investigated the effect of S. album extract on modulation of toll-like receptor 3 (TLR3) agonist polyinosnic-polycytidylic acid (PolyI:C)-induced neuroinflammatory response in human neuroblastoma cells. The TLR3-mediated immune response was differentially modulated by S. album extract in SH-SY5Y cells. In addition, treatment of cells with the conditioned medium (CM) of S. album extract significantly increased the mRNA levels of IFN-β, IFN-α, MxA and OAS-1 and decreased IL-6, CXCL8, CCL2 and IP-10. S. album extract has indirectly affected the expression of IFNs and inflammatory cytokines in SH-SY5Y cells. Furthermore, the extract was able to modulate PolyI:C-induced inflammatory response in Caco2 cells. Overall, S. album was capable to attenuate PolyI:C-induced neuroinflammatory effect through the induction of TLR2, TLR4 and the modulation of TLR negative regulators of the TRAF3, IRF3 and NF-κB pathways.

Keywords: PolyI:C; Santalum album; immunomodulation; neuroinflammation; neuroprotection; toll-like receptors.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Humans
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Plant Extracts / chemistry*
  • Santalum / chemistry*
  • Toll-Like Receptor 3 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Plant Extracts
  • TLR3 protein, human
  • Toll-Like Receptor 3