Macrophage Immune-Redox Modulation by Phenylethanoid- and Flavonoid-Rich Botanical Extracts: NF-κB/iNOS-Nrf2 Crosstalk and the Proposed Role of Buddleja globosa.

Macrophage activation depends on the balance between pro-inflammatory signaling and cytoprotective antioxidant responses. Persistent nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) activity, together with insufficient nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, promotes oxidative and nitrosative stress and contributes to chronic inflammation. Phenylethanoid- and flavonoid-rich botanical extracts may modulate this immune-redox network, but the available evidence is dispersed across plant species, extraction procedures, isolated compounds, and experimental models. This review examines the phytochemical composition and biological effects of these preparations, with particular emphasis on Buddleja globosa Hope. Evidence concerning verbascoside, luteolin, apigenin, quercetin derivatives, and other constituents is integrated with findings related to toll-like receptor 4/NF-κB signaling, iNOS-derived nitric oxide, inflammatory cytokines, reactive oxygen species, and Keap1-Nrf2-dependent cytoprotective responses. Direct evidence obtained with B. globosa extracts is distinguished from mechanistic findings generated using isolated constituents or related botanical preparations. Current studies support antioxidant and inflammation-modulating activities, but interpretation is limited by phytochemical variability, inconsistent dosing, incomplete cytotoxicity assessment, and limited use of macrophage-specific models. Future work should prioritize chemically standardized extracts, direct extract-constituent comparisons, pathway-specific validation, and formulation strategies that improve stability, reproducibility, and biological performance.