Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease

Molecules. 2020 Apr 29;25(9):2076. doi: 10.3390/molecules25092076.


The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.

Keywords: PPAR-γ; PPAR-γ agonists; coronavirus infection; cytokine storm; inflammation; metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • COVID-19
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology*
  • Cytokines / antagonists & inhibitors
  • Fish Oils / pharmacology
  • Humans
  • Ligands
  • PPAR gamma / agonists*
  • Pandemics
  • Plants, Medicinal / chemistry*
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology*
  • Seafood / analysis
  • Spices / analysis
  • Thiazolidinediones / pharmacology*


  • Cytokines
  • Fish Oils
  • Ligands
  • PPAR gamma
  • Thiazolidinediones