Polygoni cuspidati radix inhibits the activation of Syk kinase in mast cells for antiallergic activity.
The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/- 2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow-derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells.
College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Korea.
Beong Ou
BO
Lim
Jun Ho
JH
Lee
Na Young
NY
Ko
Se Hwan
SH
Mun
Jie Wan
JW
Kim
Do Kyun
DK
Kim
Ju Dong
JD
Kim
Bo Kyung
BK
Kim
Hyung Sik
HS
Kim
Erk
E
Her
Hoi Young
HY
Lee
Wahn Soo
WS
Choi
D000707:Anaphylaxis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology*; D000941:Antigens / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000201:enzymology / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D045468:Fallopia japonica / Q000737:chemistry; D006632:Histamine / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D015847:Interleukin-4 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018926:Anti-Allergic Agents; D000941:Antigens; D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D006632:Histamine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4