Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

Life Sci. 2022 Nov 15:309:121048. doi: 10.1016/j.lfs.2022.121048. Epub 2022 Oct 7.

Abstract

Pirfenidone (PFD) is a non-peptide synthetic chemical that inhibits the production of transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), platelet-derived growth factor (PDGF), Interleukin 1 beta (IL-1β), and collagen 1 (COL1A1), all of which have been linked to the prevention or removal of excessive scar tissue deposition in many organs. PFD has been demonstrated to decrease apoptosis, downregulate angiotensin-converting enzyme (ACE) receptor expression, reduce inflammation through many routes, and alleviate oxidative stress in pneumocytes and other cells while protecting them from COVID-19 invasion and cytokine storm. Based on the mechanism of action of PFD and the known pathophysiology of COVID-19, it was recommended to treat COVID-19 patients. The use of PFD as a treatment for a range of disorders is currently being studied, with an emphasis on outcomes related to reduced inflammation and fibrogenesis. As a result, rather than exploring the molecule's chemical characteristics, this review focuses on innovative PFD efficacy data. Briefly, herein we tried to investigate, discuss, and illustrate the possible mechanisms of actions for PFD to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2 candidate.

Keywords: COL1A1; COVID-19; IL-1β; PDGF; PFD; TGF-β1; TNF-α.

Publication types

  • Review

MeSH terms

  • Angiotensins
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • COVID-19 Drug Treatment*
  • Collagen Type I / metabolism
  • Fibrosis
  • Humans
  • Inflammation / drug therapy
  • Interleukin-1beta
  • Platelet-Derived Growth Factor
  • Pyridones / pharmacology
  • Pyridones / therapeutic use
  • SARS-CoV-2
  • Transforming Growth Factor beta1* / metabolism
  • Transforming Growth Factors
  • Tumor Necrosis Factor-alpha

Substances

  • Transforming Growth Factor beta1
  • pirfenidone
  • Antioxidants
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta
  • Pyridones
  • Collagen Type I
  • Anti-Inflammatory Agents
  • Platelet-Derived Growth Factor
  • Transforming Growth Factors
  • Angiotensins