Pirfenidone

Pirfenidone (PFD) is a new pyridinone compound with broad spectrum anti-fibrosis effect, which can prevent and reverse fibrosis and scar formation. Launched in 2008 by Shionogi, Japan, and approved by the US Food and Drug Administration, shionogi is the first drug to demonstrate the efficacy of Chemicalbook in idiopathic pulmonary fibrosis (IPF) through a repetitive, randomized, placebo-controlled phase iii clinical trial. The drug also has a good effect on fibrosis diseases such as renal interstitial fibrosis and liver fibrosis. At the same time, it is also widely used in renal diseases (focal segmental glomerulosclerosis), hypertrophic cardiomyopathy, adult type I multiple neurofibroma, adolescent type I multiple neurofibroma and cluster neurofibroma, diabetes mellitus with kidney disease, uterine leiomyoma phase II clinical research and so on.

PFD is an effective cytokine inhibitor that inhibits the biological activity of fibroblasts and reduces cell proliferation and matrix collagen synthesis by regulating or inhibiting certain factors. At the same time, PFD can also inhibit the secretion of inflammatory mediators, reduce lipid peroxidation, and play its anti-inflammatory and antioxidant role. 

1. The inhibition of collagen synthesis of fibroblast growth factor (bFGF), transforming growth factor beta (transforminggrowthfactor - beta, TGF - beta), connective tissue growth factor (connectivetissuegrowthfactor, CTGF and metalloproteinase tissue inhibitor 1(TIMP-1) are growth factors related to fibrotic diseases, which can promote the proliferation and growth of fibroblasts, increase the synthesis of matrix collagen and prevent the degradation of extracellular matrix (ECM). They are expressed in different degrees in the process of organ fibrosis. PFD can reduce the expression of bFGF, TGF-β, ChemicalbookCTGF and TIMP-1 in fibroblasts of lung and kidney, and is correlated with collagen synthesis and matrix reduction. The production of type ⅰ and type ⅲ collagen fibers is also closely related to the synthesis of matrix collagen. PFD decreased the expression of TGF-β and the production of type ⅰ collagen. PFD also inhibited the expression of type I collagen in pulmonary fibrosis models. In addition, PFD also inhibits the mRNA expression of type iii collagen, which can reduce the synthesis of type III collagen. 2. Anti-inflammatory effect PFD can inhibit inflammatory mediators to play its anti-inflammatory effect to varying degrees. When the inflammatory factors are overexpressed in the lung, the inflammatory response will be intensified, which thickens the alveolar wall, reduces the alveolar function, and eventually leads to fibrosis. PFD mainly plays an anti-inflammatory role by inhibiting the expression of inflammatory mediators, reducing vascular permeability, and reducing the aggregation of neutrophils and inflammatory cells, so as to prevent or slow down the fibrosis degree of organ tissues. 3. Antioxidant effect PFD exerts its antioxidant effect mainly by scavenging free radicals, inhibiting lipid peroxidation and alleviating oxidative stress.