Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages

• Published in: PloS one 2014-09, Vol.9 (9), p.e107072
• Main Authors: Zhang, Xiaoxuan, Wang, Guangji, Gurley, Emily C, Zhou, Huiping
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Apigenin - pharmacology; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Cancer therapies; Caspase; Caspase-1; Cell activation; Cells, Cultured; Chemical compounds; Chemotherapy; Chinese medicine; Cytokines; Diabetes mellitus; Disease prevention; Down-Regulation - drug effects; Down-Regulation - genetics; Flavonoids; Flavonoids - pharmacology; Health aspects; Health risks; HEK293 Cells; Humans; Immune response; Immune system; Immunoglobulins; Immunology; Infection; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - prevention & control; Inflammatory diseases; Inflammatory response; Interleukin 6; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Intracellular signalling; Kinases; Lipopolysaccharides; Liver; Liver diseases; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Medicine and Health Sciences; Metabolic disorders; Metabolism; Mice; Mitogens; mRNA stability; Natural products; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Nonsteroidal anti-inflammatory drugs; Penicillin; Pharmaceuticals; Pharmacology; Risk factors; RNA; Rodents; Sepsis; Signal Transduction - drug effects; Signal Transduction - genetics; Studies; Target recognition; Toxicity; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vegetables
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107072

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. 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. 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.