Multi-pathway targeting by natural products in chronic respiratory diseases: Opportunities, challenges, and future perspectives.

Chronic respiratory diseases (CRDs) are multifactorial disorders driven by dysregulated inflammation, oxidative stress, and tissue remodeling. Conventional single-target therapies are insufficient to halt disease progression, underscoring the demand for alternative therapeutic approaches. Natural products, including bioactive compounds, herbal extracts, and traditional Chinese medicine (TCM) formulas, are characterized by their inherent multi-target properties and represent a promising intervention strategy for CRDs. This perspective emphasizes natural products as network modulators that can simultaneously regulate multiple signaling pathways. The integration of systems biology, network pharmacology, and artificial intelligence (AI) is crucial for deciphering their polypharmacological mechanisms. The clinical translation of natural products is anticipated to benefit from the implementation of several key strategies, including multi-omics integration, AI, targeted delivery, and blockchain-based quality control. By shifting from a reductionist to a network-centric view, natural products can fulfill their potential as next-generation therapeutics for CRDs.