Investigation into the protective effects of protocatechuic acid in bleomycin-induced pulmonary remodeling and fibrosis in rats: role of MMP-2/TIMP-1 and CTGF/NOX4 pathway

Abstract Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive interstitial lung disease that results from excessive tissue repair. Production of excessive extracellular matrix (ECM) by myofibroblasts has been known as an important pathological feature in IPF. Connective tissue growth factor (CTGF) is a secreted matricellular protein modulating myofibroblast activation and ECM deposition, leading to fibrosis and tissue remodeling. Protocatechuic acid is extensively distributed in many edible nuts, vegetables, and fruits and is readily absorbed by both animals and humans. Numerous biological actions of protocatechuic acid (PCA) have been observed, including antibacterial, antidiabetic, antioxidant, and anti-inflammatory characteristics. The purpose of this study is to investigate the protective effect of PCA on bleomycin-induced pulmonary fibrosis in rats. The pathological changes of the lung and levels of malondialdehyde (MDA) and glutathione (GSH) were measured . Our results revealed that PCA decreased the oxidative production of lipid MDA and increased GSH content. Moreover, PCA suppressed the expression of inflammatory biomarkers transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α), as well as decreased collagen deposition and ECM markers alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), and metallopeptidase inhibitor 1 (TIMP-1). PCA has an anti-fibrotic effect against pulmonary fibrosis by downregulation of the CTGF/NOX4/ET-1 gene expression. Also, PCA treatment ameliorated BLM-induced lung damage by improving alveolar sac structure, reducing inflammatory cell infiltration, and preserving bronchiolar epithelial integrity, suggesting that PCA may serve as a potential treatment option for PF.