Chemical composition of tetraploid Gynostemma pentaphyllum gypenosides and their suppression on inflammatory response by NF-κB/MAPKs/AP-1 signaling pathways.

The chemical composition and anti-inflammatory activity of gypenosides isolated from tetraploid Gynostemma pentaphyllum (GP) leaves were investigated. The gypenosides accounted for 7.43 mg/g of the tested GP sample, which were composed of four major saponins including isomers of gypenoside 1 and 2 (C₄₇H₇₆O₁₈), 3 (C₄₇H₇₆O₁₇), and 4 (C₄₆H₇₄O₁₇). Pretreatment of gypenosides reduced mRNA expressions of the proinflammatory mediators in LPS-stimulated RAW264.7 macrophage cells, such as IL-6, IL-1β, COX-2, and TNF-α in a dose-dependent manner. The secreted protein levels of IL-6 and TNF-α, and NO production were also decreased by gypenosides within the concentration range of 50-200 μg/ml. Moreover, the mechanism studies demonstrated that gypenosides (200 μg/ml) treatment significantly inhibited the nuclear translocation of nuclear factor-κB and activator protein 1 (c-Fos and c-Jun) through down-regulating the phosphorylation of their upstream IκB kinase and mitogen-activated protein kinases (MAPKs), especially that of c-Jun N-terminal kinase and extracellular regulated protein kinase(JNK and ERK), but not that of the p38 MAPK. These results suggested that the gypenosides might have potential anti-inflammatory effect and use for improving human health.