Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-alpha from murine macrophages.
Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. Aqueous extract from the root of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), is reported to have antitumor and immunomodulatory activities; however, the mechanism underlying its therapeutic effect is not known. In the present study we examined the effects of CK on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the gene expression of iNOS and TNF-alpha in mouse macrophages. CK elicited a dose-dependent increase in NO and TNF-alpha production in cultured macrophages. CK significantly affected secretion at concentrations of more than 5 micrograms/ml, and its maximum effect was at concentration of 100 micrograms/ml. Reverse transcription polymerase chain reaction showed that increases in NO and TNF-alpha secretion were due to an increase in inducible NO synthase mRNA and TNF-alpha mRNA, respectively. Transient expression assays with NF-kappa B binding sites linked to the luciferase gene revealed that CK-induced increase of inducible NO synthase mRNA and TNF-alpha mRNA were mediated by the NF-kappa B transcription factor complex. These results demonstrate that CK stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappa B transactivation and this may be a mechanism whereby this herbal medicine elicits its therapeutic effects.
Choi
C Y
CY
Department of Pharmacy and Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gong-ku, Kwangju 501-759, South Korea.
Kim
J Y
JY
Kim
Y S
YS
Chung
Y C
YC
Seo
J K
JK
Jeong
H G
HG
D000818:Animals; D005260:Female; D007118:Immunoassay; D008033:Limulus Test; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012313:RNA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D009573:Nitrites; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012313:RNA; D008156:Luciferases; D001616:beta-Galactosidase