Phytochemicals from Brazilian Red Propolis: A Review of Their Anti-Inflammatory Potential

Brazilian red propolis (BRP) has emerged as a promising source of multifunctional phytochemicals with potent anti-inflammatory activity. This review provides a comprehensive analysis of the anti-inflammatory effects of BRP's bioactive compounds, their molecular targets, and their mechanisms of action. Isolated compounds from BRP (such as formononetin, biochanin A, daidzein, calycosin, medicarpin, vestitol, and neovestitol) have demonstrated the ability to modulate critical pro-inflammatory signaling pathways, including NF-κB, TLR4, JAK/STAT, and PI3K/AKT, while concurrently activating antioxidant and cytoprotective responses via the Nrf2/HO-1 axis. These effects are further supported by the suppression of pro-inflammatory cytokines, regulation of immune cell infiltration and activation, inhibition of inflammasome components such as NLRP3, induction of autophagy, and polarization of macrophages and microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype. Collectively, these findings reinforce the potential of BRP as a rich source of multifunctional phytochemicals with broad therapeutic relevance for chronic inflammation and related pathologies. Future research should address the identified knowledge gaps by employing rigorous in vitro and in vivo toxicity assessments, exploring structure-activity relationships, and leveraging advanced delivery systems to optimize bioavailability. Such methodological approaches will be essential for translating the promising biological activities of BRP compounds into clinically viable therapeutic agents.