Fig. 3

The diagram illustrates the regulatory effects of natural products on alveolar macrophage polarization during different stages of SALI progression. Alveolar macrophages, influenced by external stimuli (e.g., LPS, IFN-γ, IL-10, IL-4, IL-13), undergo M1 or M2 polarization, corresponding to the overwhelming inflammatory stage (Stage I), immune suppression stage (Stage II), and fibrosis stage (Stage III). In Stage I, natural products such as Celastrol inhibit excessive M1 macrophage polarization by targeting pathways like JAK2/STAT1, HMGB1/NF-κB, and PI3K/AKT, while alpha-Hederin not only suppresses M1 polarization but also promotes M2 polarization by regulating pathways such as JAK1/STAT3, JAK1/STAT6, and NRF2/NF-κB. In Stage II, M2 polarization dominates, leading to excessive inflammation suppression, and natural products like garlic polysaccharide modulate M2 macrophage activity. In Stage III, natural products such as eucalyptol prevent fibrosis by targeting M2 macrophage polarization pathways. Key markers and regulators of M1 and M2 macrophage polarization, including proinflammatory cytokines (e.g., TNF-α, IL-1β) and anti-inflammatory cytokines (e.g., IL-10, TGF-β), are highlighted. Green, brown, and yellow arrows represent the effects of natural products during Stages I, II, and III, respectively