Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

Sci Rep. 2017 Feb 20;7:42683. doi: 10.1038/srep42683.

Abstract

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Protein Transport
  • Pueraria / chemistry*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plant Extracts
  • Reactive Oxygen Species