Anti-Inflammatory Effect of Baicalein on Polyinosinic⁻Polycytidylic Acid-Induced RAW 264.7 Mouse Macrophages

Viruses. 2018 Apr 26;10(5):224. doi: 10.3390/v10050224.

Abstract

Baicalein (3,3&prime;,4&prime;,5,6-pentahydroxyflavone) is a well-known antioxidant found in many plants, such as in the roots of Scutellaria baicalensis. In this study, we evaluate the inhibitory effect of baicalein on the inflammatory cascade in RAW 264.7 mouse macrophages induced by viral-like material. Experimental assays used in this study included Griess reagent assay for nitric oxide (NO) production, Fluo-4 assay for intracellular calcium release, multiplex cytokine assay, and quantitative real time RT-PCR assay. To induce inflammation, RAW 264.7 cells were treated with polyinosinic⁻polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA). Baicalein at concentrations up to 100 &mu;M significantly inhibited the production of NO, IL-1&alpha;, IL-6, G-CSF, GM-CSF, VEGF, MCP-1, IP-10, LIX, and RANTES as well as calcium release in RAW 264.7 cells induced by poly I:C (50 &micro;g/mL) (all p < 0.05). Baicalein at concentrations up to 50 &mu;M also significantly inhibited mRNA expression of STAT1, STAT3, CHOP, and Fas in poly I:C-induced RAW 264.7 cells (p < 0.05). In conclusion, baicalein has anti-inflammatory effect in double-stranded RNA (dsRNA)-induced macrophages by inhibiting NO, cytokines, chemokines, and growth factors via the endoplasmic reticulum stress⁻CHOP/STAT pathway.

Keywords: CHOP; STAT; baicalein; calcium; cytokine; dsRNA; inflammation; macrophages; nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Calcium / metabolism
  • Chemokines / biosynthesis
  • Cytokines / biosynthesis
  • Flavanones / pharmacology*
  • Gene Expression Regulation / drug effects
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / biosynthesis
  • Poly I-C / adverse effects*
  • RAW 264.7 Cells
  • STAT Transcription Factors / genetics
  • Signal Transduction / drug effects
  • Transcription Factor CHOP / genetics
  • fas Receptor / genetics

Substances

  • Anti-Inflammatory Agents
  • Chemokines
  • Cytokines
  • Ddit3 protein, mouse
  • Fas protein, mouse
  • Flavanones
  • STAT Transcription Factors
  • fas Receptor
  • Transcription Factor CHOP
  • Nitric Oxide
  • baicalein
  • Poly I-C
  • Calcium