Trichosanthis Semen Suppresses Lipopolysaccharide-Induced Neuroinflammation by Regulating the NF-κB Signaling Pathway and HO-1 Expression in Microglia

Toxins (Basel). 2021 Dec 14;13(12):898. doi: 10.3390/toxins13120898.

Abstract

Neuroinflammation, which is mediated by microglia that release various inflammatory cytokines, is a typical feature of neurodegenerative diseases (NDDs), such as Alzheimer's disease and Parkinson's disease. Hence, alleviating neuroinflammation by downregulating pro-inflammatory action, and upregulating anti-inflammatory action of microglia is an efficient therapeutic target for NDDs. In this study, we evaluated whether trichosanthis semen (TS), a dried ripe seed of Trichosanthes kirilowii Maximowicz, reduces lipopolysaccharide (LPS)-induced neuroinflammation by regulating microglial responses in vitro and in vivo. Our results presented that TS reduced the release of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 via inhibition of the nuclear factor kappa B (NF-κB) signaling pathway in LPS-treated BV2 microglial cells. Moreover, TS induced anti-inflammatory mediators, such as interleukin-10, found in inflammatory zone 1, and chitinase 3-like 3 by the upregulation of heme oxygenase 1 (HO-1). We further confirmed that TS administration suppressed microglial activation, but enhanced HO-1 expression in LPS-injected mice. These results suggest that TS has anti-neuroinflammatory effects via inhibition of NF-κB signaling through the activation of HO-1, and that TS may be a therapeutical candidate for NDDs treatment.

Keywords: heme oxygenase 1; interleukin-10; neuroinflammation; nuclear factor kappa B; trichosanthis semen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lipopolysaccharides / toxicity*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Microglia / drug effects
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Seeds / chemistry*
  • Signal Transduction / drug effects
  • Trichosanthes / chemistry*

Substances

  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Plant Extracts
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Hmox1 protein, mouse