The role of flavonoid baicalein in sepsis management: A systematic review of molecular mechanisms

Sepsis is an imperative and multifaceted medical condition that occurs when the immune system overreacts to pathogens. Baicalein, a strategic dynamic flavonoid, exhibits strong antioxidant and anti-inflammatory actions across diverse syndrome models and may have beneficial properties in sepsis. This study followed the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched Embase, Scopus, PubMed, and Web of Science for relevant keywords up to 11 April 2026. From 672 articles, 25 publications (in vitro (n=14), in vivo (n=18); of which 5 studies were both in vitro and in vivo) were included in this systematic review. Most in vitro studies used lipopolysaccharide (LPS) stimulated cell models, such as RAW264.7 macrophages, AR42J cells, and HUVECs, to evaluate inflammatory responses. In vivo studies were primarily conducted in mouse and rat models of sepsis, including LPS-induced endotoxemia and cecal ligation and puncture (CLP). Mechanistic findings suggested that these effects are largely mediated by modulation of key inflammatory signaling pathways, particularly by inhibiting NF-κB–related pathways and regulating oxidative stress responses. Given the promising preclinical effects of baicalein in sepsis models but the complete absence of human data, future research must prioritize pharmacokinetic characterization and well-designed clinical trials to determine whether these experimental benefits can translate into safe and effective therapies for septic patients.