Lancemaside A from Codonopsis lanceolata modulates the inflammatory responses mediated by monocytes and macrophages.
In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κB kinase (IKK) and p65/nuclear factor- (NF-) κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Eunji
E
Kim
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Woo Seok
WS
Yang
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Ji Hye
JH
Kim
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jae Gwang
JG
Park
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Han Gyung
HG
Kim
Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea.
Jaeyoung
J
Ko
Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea.
Yong Deog
YD
Hong
Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea.
Ho Sik
HS
Rho
Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea.
Song Seok
SS
Shin
Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong 369-873, Republic of Korea.
Gi-Ho
GH
Sung
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jae Youl
0000-0001-8141-9927
JY
Cho
D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002448:Cell Adhesion; D002460:Cell Line; D002470:Cell Survival; D029745:Codonopsis / Q000737:chemistry*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D019012:Integrin beta1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000737:chemistry; D010587:Phagocytosis; D012503:Saponins / Q000737:chemistry*; D020298:U937 Cells
D000975:Antioxidants; D019012:Integrin beta1; D008070:Lipopolysaccharides; D012503:Saponins; C533150:lancemaside A; D009599:Nitroprusside; D009569:Nitric Oxide; D051550:I-kappa B Kinase