Inhibition of superoxide generation in human neutrophils by AFB-1 from Fissistigma bracteolatum

• Main Authors: Guo-Long Li, 李果濃
• Other Authors: Tsong-Long Hwang
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/88534148977652885101

碩士 === 長庚大學 === 天然藥物研究所 === 93 === 英文摘要 Neutrophils are known to play important roles in a host's defenses against invasion by microorganisms and in the pathogenesis of various diseases such as rheumatoid arthritis, ischemia-reperfusion injury, chronic obstructive pulmonary disease, and asthma. In response to diverse stimuli, activated neutrophils secrete a series of cytotoxins, such as the superoxide anion, a precursor of other reactive oxygen species, granule proteases, and bioactive lipids. Suppression of the extensive or inappropriate activation of neutrophils using drugs has been proposed as a way to ameliorate these inflammatory diseases. In a search for new anti-inflammatory agents, the effect of 15 pure compounds isolated from Fissistigma sp. on respiratory burst and degranulation in human neutrophils was tested. Among then, 6-hydroxy-5,7,8-trimethoxy-2-phenyl-chroman-4-one (AFB-1), isolated from the root of Fissistigma bracteolatum, showed the most-potent inhibitory effect on superoxide anion formation in formyl-L-methionyl-L-leucyl-Lphenylalanine (fMLP)-activated human neutrophils with an IC50 value of 0.34 ± 0.03 μM. In contrast, it failed to alter the subcellular NADPH oxidase activity, and it did not display antioxidant and superoxide anion-scavenging ability. Additionally, AFB-1 inhibited phosphorylation of ERK1/2 but not p38 MAPK in fMLP-induced human neutrophils. However, neither the protein kinase C activator–induced superoxide anion release nor the fMLP-stimulated elastase release and calcium mobilization was significantly inhibited by AFB-1. The inhibition of superoxide anion production in fMLP-stimulated human neutrophils by AFB-1 was reversed by protein kinase (PK)A inhibitors. Moreover, AFB-1 induced cAMP formation in human neutrophils. In summary, these results indicate that the inhibitory effect of AFB-1 on human neutrophil respiratory burst is through the cAMP- and ERK 1/2-dependent pathways, but not via the p38 and calcium-dependent pathways.