Thus, endogenous A2AR may not play a role in regulating the wave pattern

acterized inducer of the inflammatory response. The initial acute innate immune response to LPS primes the adaptive immune system against further infection. Macrophages are the major players in both innate and adaptive inflammatory responses. It has been well-recognized that the prolonged activation of the inflammatory response contributes to a wide variety of chronic human diseases such as arteriosclerosis, sepsis, obesity, diabetes, various liver diseases, inflammatory bowel disease, autoimmune diseases, allergy and cancer. Activation of macrophages by LPS leads to the increased secretion of a large set of proinflammatory cytokines, such as tumor necrosis factor -alpha, interleukin -1, IL-6, and macrophage chemoattractant protein-1. Persistent production of these proinflammatory cytokines can cause severe tissue destruction and eventually organ failure. The traditional steroidal anti-inflammatory drugs and nonsteroidal antiinflammatory PubMed ID: drugs are the commonly used to treat acute inflammatory disorders. However, these conventional drugs have not been successful in treating chronic inflammatory diseases due to severe side effects. The need for the development of new anti-inflammatory drugs with higher potency and lower toxicity is urgent to combat various Digitoxin site complex inflammatory diseases. Flavonoids are a family of polyphenolic compounds, that are widely distributed in the plant kingdom and consumed in significant amounts as part of the human diet. The beneficial effects of these flavonoids to human health have been welldocumented. Epidemiological studies have shown that Anti-Inflammatory Effect of Apigenin flavonoids in a healthy diet have potentially beneficial effects in inflammatory diseases and can reduce the risk of various cancers. Apigenin is a non-toxic and non-mutagenic dietary flavonoid, which is abundantly present in common fruits and vegetables, such as oranges, grapefruits, parsley, onions, chamomile, wheat sprouts, and some seasonings. During last decade, apigenin has garnered increased interest as a health promoting agent because of its low intrinsic toxicity and high chemopreventive efficiency. It has been shown that apigenin induces human pancreatic cancer cell death via inhibition of the glycogen synthase kinase-3b/nuclear factor kappa B signaling pathway. In addition, apigenin has been reported to have anti-inflammatory activities. It protects endothelial cells from LPS-induced inflammation and inhibits allergen-induced airway inflammation. Several intracellular signaling pathways have been suggested to be involved in apigenin-mediated anti-inflammatory effects, such as NF-kB, MAPK/ERK, and JNK pathways. However, the cellu- lar/molecular mechanisms by which apigenin modulates LPSinduced inflammatory response in macrophages have not been fully revealed. In the present study, we examined the effect of apigenin on LPS-induced inflammatory response in macrophages and further explored the potential cellular/molecular mechanisms involved in its anti-inflammatory effects. Methods Materials Apigenin, LPS, phorbol 12-myristate 13-acetate, actinomycin D, and hygromycin B were purchased from Sigma-Aldrich. Cell Counting Kit-8 PubMed ID: was from Dojindo Molecular Technologies. Immune Response Tier 1 H96 Plate, Bio-Rad protein assay reagent, Precision Plus Kaledoscope Standards, iQTM SYBR Green Supermix were obtained from Bio-Rad. QIAzol Lysis Reagent was obtained from QIAGEN Sciences. High Capacity cDNA Reverse Transcription Kit was from Life