Involvement of TLR2 and TLR9 in the anti-inflammatory effects of chlorogenic acid in HSV-1-infected microglia

Life Sci. 2015 Apr 15;127:12-8. doi: 10.1016/j.lfs.2015.01.036. Epub 2015 Mar 2.


Aims: There is no effective medication to date for herpes simplex virus encephalitis (HSE). In this study, we investigated the anti-inflammatory effect of chlorogenic acid (CGA) on herpes simplex virus (HSV)-1-induced responses in BV2 microglia.

Main methods: The cellular model was established with BV2 cells stimulated by HSV-1 and then treated with CGA at different concentrations. Cell viability was assayed by the MTT assay. The mRNA expression of Toll-like receptor (TLR)-2, TLR9 and myeloid differentiation factor88 (Myd88) was assayed by real-time quantitative PCR, and the protein expression was assayed by flow cytometry or Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured by ELISA as well as real-time quantitative PCR. Nuclear NF-κB p65 protein was assayed by Western blotting.

Key findings: The cell survival rate was significantly improved after CGA treatment, and CGA prevented increases in TLR2, TLR9 and Myd88 following HSV-1 challenge in BV2 cells both at the mRNA and protein levels. Moreover, CGA could attenuate HSV-induced TNF-α and IL-6 release into the supernatant. The mRNA levels of TNF-α and IL-6 were also significantly inhibited by CGA. The expression of NF-κB p65 increased significantly in the nucleus in HSV-1-stimulated microglia but could be reduced by CGA.

Significance: CGA inhibits the inflammatory reaction in HSE via the suppression of TLR2/TLR9-Myd88 signaling pathways. CGA may serve as an anti-inflammatory agent and provide a new strategy for treating HSE.

Keywords: Chlorogenic acid; Herpes simplex virus-1; Inflammation; Toll-like receptor 2; Toll-like receptor 9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chlorogenic Acid / pharmacology*
  • Cytokines / metabolism
  • Herpes Simplex / pathology*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human*
  • Humans
  • Interleukin-6 / metabolism
  • Microglia / drug effects*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects
  • Toll-Like Receptor 2 / biosynthesis
  • Toll-Like Receptor 2 / drug effects*
  • Toll-Like Receptor 9 / biosynthesis
  • Toll-Like Receptor 9 / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-6
  • NF-kappa B
  • Toll-Like Receptor 2
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Chlorogenic Acid