Lancemaside A fromCodonopsis lanceolataModulates the Inflammatory Responses Mediated by Monocytes and Macrophages

Abstract

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.

21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner

“…Interestingly, ATS-E3 blocked phagocytosis of FITC-dextran in a dose-dependent manner (Figure 2(b), left panel). Moreover, the IKK inhibitor BAY 11-7082 also significantly diminished the uptake of FITC-dextran, indicating that phagocytosis of FITC-dextran by macrophages is dependent on IKK/NF- κ B (Figure 2(b), right panel), as reported previously [32]. Additional functions of macrophages include the release of large amounts of toxic molecules such as ROS and RNS, which cause cellular damage in tissues or organs and lead to loss of function due to inflammation [33].…”

The genus Codonopsis (Campanulaceae): a review of phytochemistry, bioactivity and quality control

“…Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell–cell adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin antibody, and immobilized cell-fibronectin. These findings suggested that the anti-inflammatory mechanism of lancemaside A involves the suppression of the cellular responses of macrophages and monocytes by blocking redox activation and the IKK/NF-κB pathway [ 78 ].…”

Codonopsis lanceolata: A Review of Its Therapeutic Potentials

“…Additionally, when treated with sodium nitroprusside, a radical generator, lancemaside A lessened the phagocytic activity and enhanced the neutralizing capacity of RAW264.7 cells. Furthermore, lancemaside A and saponin fraction (SF) blocks the adhesion activity of RAW264.7 cells, inhibits anti‐β1‐integrin triggered cell‐cell adhesion of U937 cells, and immobilizes cell fibronectin (Byeon et al ., ; Kim et al ., ). These outcomes imply that the strong antiinflammatory mechanisms of lancemaside A and SF are because of the suppression of macrophage and monocyte cellular responses by obstructing redox activation and the IKK/NF‐κB pathway (Kim et al ., ).…”

“…Furthermore, lancemaside A and saponin fraction (SF) blocks the adhesion activity of RAW264.7 cells, inhibits anti‐β1‐integrin triggered cell‐cell adhesion of U937 cells, and immobilizes cell fibronectin (Byeon et al ., ; Kim et al ., ). These outcomes imply that the strong antiinflammatory mechanisms of lancemaside A and SF are because of the suppression of macrophage and monocyte cellular responses by obstructing redox activation and the IKK/NF‐κB pathway (Kim et al ., ). The n ‐butanol fraction (BuOH or BF) of C. lanceolata (200 µg/mL) upregulates mRNA expression of granulocyte‐macrophage colony stimulating factor (GM‐CSF) as well as increases splenocyte proliferation.…”