RESEARCH - Potent inhibition of superoxide anion production in activated human neutrophils by isopedicin, a bioactive component of the Chinese medicinal herb Fissistigma oldhamii

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Free Radic Biol Med. 2009 Feb 15;46(4):520-8. Epub 2008 Dec 6.

Potent inhibition of superoxide anion production in activated human

neutrophils by isopedicin, a bioactive component of the Chinese

medicinal herb Fissistigma oldhamii.

Hwang TL, Li GL, Lan YH, Chia YC, Hsieh PW, Wu YH, Wu YC.

Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan.

Fissistigma oldhamii is widely used in traditional Chinese medicine to

treat rheumatoid arthritis. Activation of neutrophils is a key feature

of inflammatory diseases. Herein, the anti-inflammatory functions of

isopedicin, a flavanone derived from F. oldhamii, and its underlying

mechanisms were investigated in human neutrophils. Isopedicin potently

and concentration-dependently inhibited superoxide anion (O(2)(*)(-))

production in formyl-L-methionyl-L-leucyl-L-phenylalanine

(FMLP)-activated human neutrophils with an IC(50) value of 0.34+/-0.03

microM. Furthermore, isopedicin displayed no superoxide-scavenging

ability, and it failed to alter subcellular NADPH oxidase activity.

The inhibitory effect of isopedicin on O(2)(*)(-) production was

reversed by protein kinase A (PKA) inhibitors. Moreover, isopedicin

increased cAMP formation and PKA activity in FMLP-activated human

neutrophils, which occurred through the inhibition of

phosphodiesterase (PDE) activity but not an increase in adenylate

cyclase function. In addition, isopedicin reduced FMLP-induced

phosphorylation of extracellular regulated kinase and c-Jun N-terminal

kinase, which was reversed by the PKA inhibitor. In contrast,

isopedicin failed to alter FMLP-induced phosphorylation of p38

mitogen-activated protein kinase and calcium mobilization. In summary,

these results demonstrate that inhibition of O(2)(*)(-) production in

human neutrophils by isopedicin is associated with an elevation of

cellular cAMP and activation of PKA through its inhibition of

cAMP-specific PDE.

PMID: 19100830

http://www.ncbi.nlm.nih.gov/pubmed/19100830

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