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DOI: 10.1055/s-0033-1352257
Isolation of caffeic acid derivatives and their anti-inflammatory effects in raw 264.7 cells from Parasenecio firmus
It is well known that the pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) are involved in several inflammatory diseases and lipopolysaccharide (LPS) can stimulate these inflammatory responses. Caffeic acid derivatives (CAD) are treated as important anti-inflammatory chemicals. The aim of this study is to investigate isolation and anti-inflammatory effects of CAD which are the major compounds of Parasenecio firmus. Bioassay-guided separation on methanol extract of P. firmus using the multiple chromatography steps resulted in the isolation of three CAD that are identified as 3,5-caffeoylquinic acid, 4,5-dicaffeoylquinic acid and 5-caffeoylquinic acid (5-CQA). The anti-inflammatory effects of CAD were investigated via study on the molecular mechanisms in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells. CAD dose-dependently reduced the productions of NO and PGE2 induced by LPS. It was found that 5-CQA showed the highest inhibition on NO production in RAW 264.7 cells. In addition, 5-CQA significantly suppressed the LPS induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) at the mRNA and protein levels. These results were strongly supported by decrease in DNA binding of nuclear factor-kappa B (NF-κB) and nuclear translocation of p65 and p50 subunits of NF-κB. in addition, 5-CQA dose-dependently reduced the production of IL-6, IL-1β and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. Thus, these results suggest that the anti-inflammatory activity of 5-CQA is associated with the down-regulation of iNOS, COX-2 and TNF-α through the negative regulation of the NF-κB pathway in RAW 264.7 cells.