Astragalus saponins Inhibits Lipopolysaccharide-Induced Inflammation in Mouse Macrophages.
Excessive nitric oxide (NO) and pro-inflammatory cytokines are produced during the pathogenesis of inflammatory diseases and cancer. It has been demonstrated that anti-inflammation contributes Astragalus membranaceus saponins (AST)'s beneficial effects in combination of conventional anticancer drugs. However, the immunomodulating property of AST has not been well characterized. In this study, we found that AST suppressed lipopolysaccharide (LPS)-induced generation of NO without causing cytotoxicity in the mouse macrophage RAW264.7. The gene and protein overexpression of inducible NO synthase (iNOS) as well as the production of tumor necrosis factor-[Formula: see text], evoked by LPS, was consistently down-regulated by AST. AST also inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and suppressed nuclear factor (NF)-[Formula: see text]B activation and the associated I[Formula: see text]B[Formula: see text] degradation during LPS insult. Furthermore, AST induced growth inhibition in promyelocytic leukemic HL-60 cells and T-lymphocyte leukemic Jurkat cells, but exerted no cytotoxic effects in normal human peripheral blood mononuclear cells (PBMC). It is known that the chemotherapeutic drug 5-FU can suppress the immune system, which can be identified by a reduced white blood cell count and decreased hematocrit, while the combination of AST and 5-FU can reverse the above hematologic toxicities. To summarize, non-cytotoxic concentrations of AST suppress LPS-induced inflammatory responses via the modulation of p38 MAPK signaling and the inhibition of NO and cytokine release. Importantly, AST can alleviate the hematologic side effects of current chemotherapeutic agents. These findings can facilitate the establishment of AST in the treatment of inflammatory diseases and inflammation-mediated tumor development.
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Yue
Y
Wang
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Tianjing
T
Ren
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Lucong
L
Zheng
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Hubiao
H
Chen
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Joshua Kashun
JK
Ko
* Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.
Kathy Kawai
KK
Auyeung
D000818:Animals; D027885:Astragalus propinquus; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D000067996:RAW 264.7 Cells; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C027492:Huang Qi; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases
Astragalus saponins; Cytokines; Lipopolysaccharide; Mitogen-Activated Protein Kinase; Nitric Oxide; Nuclear Factor-B