Effects of luteolin on sepsis: A comprehensive systematic review

Sepsis and septic shock are the main causes of mortality and complications in intensive care units all over the world. Luteolin is thought to have a significant role as a free radical scavenger, an anti-inflammatory agent, and an immune system modulator. The object of this review is to conduct a systematic review of the effects of luteolin and its mechanisms of action in the treatment of sepsis and its complications. The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines (PROSPERO: CRD42022321023). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Out of 1,395 records screened, 33 articles met the study criteria. In the collected papers, the main reported findings are that luteolin can affect inflammation-initiating pathways such as toll-like receptors and high mobility group box-1 and reduces the expression of genes that produce inflammatory cytokines, such as the Nod receptor protein-3, and nuclear factor kappa-light chain-enhancer of activated B cells. Luteolin also reduces the overactivity of macrophages, neutrophil extracellular traps and lymphocytes by regulating the immune response. Most studies revealed luteolin's positive benefits on sepsis through several pathways. Luteolin showed the capacity to reduce inflammation and oxidative stress, control immunological response, and prevent organ damage (in vivo studies) during sepsis. Large-scale in vivo experiments are necessary to elucidate its potential impacts on sepsis.