Scutellarin Attenuates Microglia Activation in LPS-Induced BV-2 Microglia via miRNA-7036a/MAPT/PRKCG/ERK Axis

Adv Biol (Weinh). 2024 Jul;8(7):e2400123. doi: 10.1002/adbi.202400123. Epub 2024 Apr 29.

Abstract

Scutellarin is an herbal agent which can exert anti-neuroinflammatory effects in activated microglia. However, it remains uncertain if it can inhibit microglia-mediated neuroinflammation by regulating miRNAs. This study sought to elucidate the upstream regulatory mechanisms by endogenous microRNAs and its target gene in activated microglia in lipopolysaccharide (LPS)-induced BV-2 microglia. Results show that scutellarin suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) significantly in LPS-stimulated BV-2 microglia. As with the results of miRNAs function classification in vitro, the expression levels of mir-7036a-5p are upregulated in LPS-activated BV-2 microglia, but are downregulated by scutellarin. Rescue experiments indicated that mir-7036a-5p is a pro-inflammatory factor in activated BV-2 microglia. mir-7036a-5p agomir promoted the expression of phosphorylated tau proteins (p-tau), protein kinase C gamma type (PRKCG), extracellular regulated protein kinases (ERK1/2), but the is reversed by mir-7036a-5p antagomir in vitro. It is shown here that mir-7036a-5p is involved in microglia-mediated inflammation in LPS-induced BV-2 microglia. More important is the novel finding that scutellarin mitigated microglia inflammation by down-regulating the mir-7036a-5p/MAPT/PRKCG/ERK signaling pathway.

Keywords: inflammation; miRNAs; microglia; scutellarin.

MeSH terms

  • Animals
  • Apigenin* / pharmacology
  • Cell Line
  • Glucuronates* / pharmacology
  • Lipopolysaccharides* / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microglia* / drug effects
  • Microglia* / metabolism
  • Protein Kinase C / metabolism

Substances

  • Apigenin
  • scutellarin
  • Glucuronates
  • Lipopolysaccharides
  • MicroRNAs
  • Protein Kinase C