Emerging molecular targets and natural therapeutics for idiopathic pulmonary fibrosis: Insights into mechanisms, risks, and COVID-19 links.

Pulmonary fibrosis, often termed as idiopathic pulmonary fibrosis (IPF), is a leading cause of death for patients with lung damage, acute respiratory distress syndrome, and even Coronavirus disease. This article focuses on key factors, such as transforming growth factor, fibroblast growth factors, Neurogenic locus notch homolog (Notch), and Sonic hedgehog, involved in the progression of IPF. Historically, our understanding of IPF's impacts on the immune system that was limited due to the complexity. Recent reports, however provided valuable insights into defence mechanisms and factors. We highlight various factors of pulmonary fibrosis. Here, we will discuss the impact of diverse risk factors, including anticancer agents such as bleomycin and methotrexate; mineral silica; and metals like arsenic, aluminium and copper, which have been identified as potential triggers of pulmonary fibrosis. Current treatment strategies for IPF are not fully effective, and the mechanism of the disease remains poorly understood. This review will also discuss the role of natural phytocompounds, including steroidal saponin, stilbenoid polyphenol resveratrol, safflomin of Carthamus tinctorius or safflower yellow, along with several genetic modulation approaches in addressing IPF. Finally, we examine the aspects and associations of IPF and SARS-CoV-2 to better understand disease severity, causes, and associated comorbidities.