Protective role of natural products in pulmonary fibrosis through immune regulation

Pulmonary fibrosis (PF) is a progressive, fatal fibrotic disease caused by respiratory conditions. The condition can ultimately lead to severe organ failure and mortality, and is associated with multiple risk factors. Growing evidence highlights the immune system’s role in PF, with various immune components participating in inflammatory and fibrotic processes. Different immune cells, including neutrophils, lymphocytes, and macrophages, demonstrate distinct effects on PF progression and development. Furthermore, key immune system cytokines, including the interleukin (IL) family, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, and connective tissue growth factor (CTGF), contribute to PF initiation and progression through independent mechanisms and mutual regulation. Currently, limited effective treatments exist for PF, with several treatments causing severe adverse reactions. Natural products, characterized by multi-target effects, holistic regulation, and low toxicity, have emerged as a research focus. This review compiles the mechanisms, therapeutic potential, and active components of various natural products. These compounds can ameliorate pulmonary inflammation, epithelial-mesenchymal transition, and collagen deposition through diverse immune mechanisms, acting at specific stages or throughout the fibrotic process, thereby supporting PF management. This review examines current scientific understanding of natural products’ immunological effects in PF, which is crucial for developing future anti-PF therapeutics.