title: Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages.
abstract: BACKGROUND
  Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood.
  
  
  RESULTS
  In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB.
  
  
  CONCLUSIONS
  Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China; Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Gurley
authors.affiliation: Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Internal Medicine/Gastroenterology and McGuire Veterans Affairs Medical Center, Richmond, Virginia, United States of America; School of Pharmacy, Wenzhou Medical University, Wenzhou, P. R. China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047310:Apigenin