Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-α 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 mug/ml, and its maximum effect was at concentration of 100 mug/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-kappaB 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-kappaB 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-kappaB transactivation and this may be a mechanism whereby this herbal medicine elicits its therapeutic effects. (C) 2001 Elsevier Science B.V, All rights reserved.