PT  - JOURNAL ARTICLE
AU  - Yuh-Chiang Shen
AU  - Cheng-Jen Chou
AU  - Wen-Fei Chiou
AU  - Chieh-Fu Chen
TI  - Anti-Inflammatory Effects of the Partially Purified Extract of Radix <em>Stephaniae tetrandrae</em>: Comparative Studies of Its Active Principles Tetrandrine and Fangchinoline on Human Polymorphonuclear Leukocyte Functions
AID  - 10.1124/mol.60.5.1083
DP  - 2001 Nov 01
TA  - Molecular Pharmacology
PG  - 1083--1090
VI  - 60
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/60/5/1083.short
4100  - http://molpharm.aspetjournals.org/content/60/5/1083.full
SO  - Mol Pharmacol2001 Nov 01; 60
AB  - We hypothesized that prevention of neutrophil from activation may underlie the myocardial protective effect of the specially processed extract of radix Stephaniae tetrandrae (SPRST). Inflammatory responses in isolated peripheral human neutrophils were studied in the presence or absence of SPRST. SPRST (1–10 μg/ml) concentration-dependently preventedN-formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene B4 (LTB4)-induced neutrophil adhesion and transmigration. Comparable results were also observed in neutrophils pretreated with fangchinoline (Fan) or tetrandrine (Tet), two active components in SPRST. It has been reported that neutrophil adhesion/transmigration is mainly Mac-1 (CD11b/CD18)-dependent and could be modulated by reactive oxygen species (ROS) production. SPRST, Tet, and Fan diminished fMLP- or LTB4-induced Mac-1 up-regulation and ROS production. SPRST, Fan, Tet, and verapamil impaired fMLP-induced rapid intracellular alkalization, an essential mechanism for neutrophil ROS production, and [Ca2+]i increment, suggesting that a calcium dependent pathway might be involved. Direct G protein activation by AlF4 − also triggered [Ca2+]i increment and adhesion that could be abolished by pertussis toxin and were partially reversed by SPRST, Fan, and Tet. These results reveal that inhibition of neutrophil adhesion and transmigration may account for SPRST's myocardial protective effect. This effect of SPRST may be mediated by component(s) in addition to Tet and Fan because combination of 0.1 μg/ml of Tet and Fan did not mimic the effect of SPRST. We conclude that SPRST exerts anti-inflammatory effects by interfering with ROS production and Ca2+ influx through G protein modulation to prevent Mac-1 up-regulation in neutrophil activation.