Objective:

To synthesize current preclinical and clinical evidence regarding the mechanisms through which natural products and traditional botanical formulas modulate macrophage polarization in idiopathic pulmonary fibrosis (IPF).

Approach:

• Narrative Review: The review examines the role of purified phytochemicals and multicomponent botanical formulas in modulating the immune microenvironment of pulmonary fibrosis.

Key Findings:

• Conventional antifibrotics like nintedanib and pirfenidone show limited efficacy in reversing established fibrosis and frequently cause dose-limiting toxicities.
• Macrophages exhibit significant heterogeneity and plasticity, playing a critical role in the fibrotic niche during IPF progression.
• Natural therapeutics can target multiple pathways simultaneously, potentially suppressing profibrotic macrophage polarization and reducing oxidative stress.

Interpretation:

The review emphasizes the complexities of the fibrotic niche in IPF and the potential for multi-targeted therapeutic strategies.

Limitations:

• Current understanding relies on preclinical models, necessitating further empirical validation.
• The review does not provide clinical trial data for the discussed natural products.

Conclusion:

Natural product-based therapeutics represent a promising investigational approach for modulating the fibrotic niche in IPF.