Dichroa febrifuga Lour. inhibits the production of IL-1beta and IL-6 through blocking NF-kappaB, MAPK and Akt activation in macrophages.
OBJECTIVE
The roots of Dichroa febrifuga Lour. have been used as a traditional antimalarial drug and also used in the treatment of productive cough and unstable fever caused by infection in China and Korea. In this study, we evaluated the anti-inflammatory effect and underlying molecular mechanism of aqueous extract of Dichroa febrifuga (AEDF) in C57BL/6 mouse peritoneal macrophages.


METHODS
The effect of AEDF on proinflammatory cytokine (IL-1beta and IL-6) production was analyzed by ELISA and real-time RT-PCR. The effects of AEDF on NF-kappaB/IkappaB-alpha/IKK were measured by reporter assay (in RAW 264.7 cells), EMSA, Western blotting and kinase assay. The effects of AEDF on Akt and MAPKs activity were assayed by Western blotting.


RESULTS
AEDF inhibited the production of IL-1beta and IL-6, NF-kappaB activation, IkappaB-alpha degradation, and IKK, Akt, ERK1/2 and JNK activities in LPS-stimulated mouse peritoneal macrophages.


CONCLUSIONS
These results suggest that AEDF inhibits proinflammatory cytokine (IL-1beta and IL-6) production in LPS-stimulated mouse peritoneal macrophages, and that these effects are mediated by the inhibition of the activity of IKK/IkappaB/NF-kappaB and the phosphorylation of Akt, ERK1/2, and JNK. Our results provide a molecular basis for understanding the inhibitory effects of Dichroa febrifuga roots on endotoxin-mediated inflammation.
Park
Sun Young
SY
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Keumjeong-gu, Pusan 609-735, Republic of Korea.
Park
Ga-Young
GY
Ko
Woo Shin
WS
Kim
Younghee
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D029628:Hydrangeaceae; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors; C000606205:Nfkbia protein, mouse