Modulation of Lipopolysaccharide Stimulated Nuclear Factor kappa B Mediated iNOS/NO Production by Bromelain in Rat Primary Microglial Cells

Iran Biomed J. 2016;20(1):33-40. doi: 10.7508/ibj.2016.01.005. Epub 2015 Oct 13.

Abstract

Background: Microglial cells act as the sentinel of the central nervous system .They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation.

Methods: Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain.

Results: Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death.

Conclusion: Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases.

Keywords: Ananas; Microglia; NF-kappa B; Neuroimmunomodulation; Nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bromelains / pharmacology*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides / toxicity*
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / biosynthesis
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / biosynthesis
  • Rats

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • Bromelains
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat