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

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.

Graphical abstract

Fig. 1

Schematic diagram showing how the imbalance between profibrotic cytokines and the anti-fibrotic cytokines resulted in Excessive ECM deposition, activation of inflammatory pathway, and secretion of proinflammatory cytokines.

Fig. 2

Schematic diagram illustrates how injury participates in mitochondrial dysfunction, ROS release, activation of the apoptosis pathway, and DNA fragmentation.

Fig. 3

Injury triggers the migration of inflammatory cells, the recruitment of fibroblasts, the growth of myofibroblasts, the production of extracellular matrix, and the deposition of collagen.

Fig. 4

Diagrammatic representation of the antifibrotic action of PFD against pulmonary fibrosis by inhibition of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and interleukin 1 beta (IL1β).

Fig. 5

Myofibroblast differentiation and functions of myofibroblasts after cardiac injury.

Fig. 6

Schematic diagram showing the effect of fibrogenic mediators on the induction of kidney fibrosis.

Fig. 7

Schematic diagrams showing how PFD protects against liver fibrosis through inhibiting TNF-α, TGF-β, IL6, IFNɣ, and α-SMA.

Fig. 8

Potential mechanisms for the suppression of fibrogenesis by PFD.

Fig. 9

Inflammatory response occurring during COVID-19 infection.