The mitigating effect of para‐hydroxycinnamic acid in bleomycin‐induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways

Abstract This study investigated the therapeutic benefits of para ‐hydroxycinnamic acid in mice with bleomycin‐induced lung fibrosis. Forty male BALB/c mice were randomly assigned to four groups: normal, which received 0.9% normal saline; induced, which received a single dose of bleomycin (5 mg/kg) by oropharyngeal challenge; pirfenidone‐treated; and para ‐hydroxycinnamic acid‐treated, which challenged with bleomycin and received a daily oral dose of 300 and 50 mg/kg, respectively, from day 7 to day 21. Tissue pro‐fibrotic and inflammatory cytokines, oxidative indicators, pulmonary histopathology, immunohistochemistry of fibrotic proteins and the assessment of gene expression by RT‐qPCR were evaluated on day 22 after euthanizing animals. Pirfenidone and para ‐hydroxycinnamic acid managed to alleviate the fibrotic endpoints by statistically improving the weight index, histopathological score and reduced expression of fibrotic‐related proteins in immune‐stained lung sections, as well as fibrotic markers measured in serum samples. They also managed to alleviate tissue levels of oxidative stress and inflammatory and pro‐fibrotic mediators. para ‐Hydroxycinnamic acid enhanced the expression of crucial genes associated with oxidative stress, inflammation and fibrosis in vivo. para ‐Hydroxycinnamic acid has demonstrated similar effectiveness to pirfenidone, suggesting it could be a promising treatment for fibrotic lung conditions by inhibiting the TGF‐β1/Smad3 pathway or through its anti‐inflammatory and antioxidant properties.