Pirfenidone (AMR69) is an orally active antifibrotic drug that attenuates the production of chemokines CCL2 and CCL12 in fibrocytes[1]. Pirfenidone is a synthetic pyridone drug used to treat idiopathic pulmonary fibrosis (IPF) and also has anti-inflammatory and antioxidant properties [2].
In vitro, pirfenidone (1-10 mM) treatment of human glioma cell lines (LN-18, T98G, LNT-229, and LN-308) for 48 h reduced cell proliferation in a concentration-dependent manner, reduced the levels of the intracellular cytokine transforming growth factor (TGF-β), and reduced the levels of matrix metalloproteinase (MMP-11) [3]. Pirfenidone (2mg/mL) treated intestinal fibroblasts (p-hIFs) for 72 hours reversibly inhibited cell proliferation, inhibited the expression of extracellular matrix proteins (ECM), and inhibited the phosphorylation of the TGF-β1/mTOR/p70S6K signaling pathway mediated by TGF-β1[4].
In vivo, oral treatment of chronic graft-versus-host disease (cGVHD) mice with pirfenidone (400 mg/kg) effectively reduced macrophage infiltration and TGF-β production, and reduced fibrosis and tissue damage in the skin and visceral organs[5]. Oral treatment of idiopathic pulmonary fibrosis (IPF) mice with pirfenidone (300 mg/kg) significantly slowed the progression of pulmonary fibrosis, reduced the mRNA levels of TGF-β, fibronectin and other fibrosis-related genes, and reduced collagen deposition[6].
References:
[1] Inomata M, Kamio K, Azuma A, et al. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis[J]. Respiratory research, 2014, 15: 1-14.
[2] Antar S A, Saleh M A, Al-Karmalawy A A. 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[J]. Life Sciences, 2022, 309: 121048.
[3] Burghardt I, Tritschler F, Opitz C A, et al. Pirfenidone inhibits TGF-β expression in malignant glioma cells[J]. Biochemical and biophysical research communications, 2007, 354(2): 542-547.
[4] Cui Y, Zhang M, Leng C, et al. Pirfenidone inhibits cell proliferation and collagen I production of primary human intestinal fibroblasts[J]. Cells, 2020, 9(3): 775.
[5] Du J, Paz K, Flynn R, et al. Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production[J]. Blood, The Journal of the American Society of Hematology, 2017, 129(18): 2570-2580.
[6] Duerr J, Leitz D H W, Szczygiel M, et al. Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice[J]. Nature communications, 2020, 11(1): 2012.
吡非尼酮（Pirfenidone；AMR69）是一种具有口服活性的抗纤维化药物，可减弱纤维细胞中趋化因子CCL2和CCL12的产生[1]。Pirfenidone是一种合成吡啶酮药物，用于治疗特发性肺纤维化（IPF），还具有抗炎和抗氧化特性[2]。
在体外，Pirfenidone（1-10 mM）处理人神经胶质瘤细胞系（LN-18、T98G、LNT-229和LN-308）48h，浓度依赖性地降低了细胞增殖，降低了胞内细胞因子转化生长因子（TGF-β）的水平，还降低了基质金属蛋白酶（MMP-11）的水平[3]。Pirfenidone（2mg/mL）处理肠道成纤维细胞（p-hIFs）72h，可逆地抑制细胞的增殖，抑制细胞外基质蛋白（ECM）的表达，抑制TGF-β1介导的 TGF-β1/mTOR/p70S6K信号通路的磷酸化[4]。
在体内，Pirfenidone（400mg/kg）通过口服治疗慢性移植物抗宿主病（cGVHD）小鼠，有效减少巨噬细胞浸润和TGF-β的产生，减少皮肤和内脏器官纤维化和组织损伤[5]。Pirfenidone（300mg/kg）通过口服治疗特发性肺纤维化（IPF）小鼠，显著减缓了肺纤维化的进展，降低了TGF-β、纤连蛋白和其他纤维化相关基因的 mRNA水平，减少了胶原蛋白沉积[6]。