Andrograpanin, isolated from Andrographis paniculata, exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways.
Andrographis paniculata Nees is an official herbal medicine for treatment of infection and inflammation in China. Andrograpanin, the one of diterpene lactones in A. paniculata, is a hydrolysate from neoandrographolide in vivo and in vitro. The goal of the present study was to investigate andrograpanin which effects on over production of nitric oxide (NO) and pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-12p70) and the key signaling pathways involved in lipopolysaccharide (LPS)-activated macrophage cells. The results showed that NO and all three pro-inflammatory cytokines were inhibited by andrograpanin (15-90 microM) in a dose-dependent manner. The RT-PCR and western blotting assays showed that andrograpanin inhibited productions of NO and pro-inflammatory cytokines through down-regulating iNOS and pro-inflammatory cytokines gene expression levels. Further studies suggested that down-regulation of p38 mitogen-activated protein kinase (MAPKs) signaling pathways were involved in the anti-inflammatory activities of andrograpanin. This study provided evidences that andrograpanin might be useful as a potential anti-inflammatory leading compound for inflammatory drug development.
Liu
Jun
J
Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Institute of Chinese material Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Wang
Zheng-Tao
ZT
Ge
Bao-Xue
BX
D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C530537:andrograpanin; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases