Astragalus saponins Inhibits Lipopolysaccharide-Induced Inflammation in Mouse Macrophages

Yue Wang, Tianjing Ren, Lucong Zheng, Hubiao CHEN, Joshua KO*, Kathy K W AU YEUNG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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-α, 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)-κB activation and the associated IκBα 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.

Original languageEnglish
Pages (from-to)579-593
Number of pages15
JournalAmerican Journal of Chinese Medicine
Volume44
Issue number3
DOIs
Publication statusPublished - 2016

Scopus Subject Areas

  • Complementary and alternative medicine

User-Defined Keywords

  • Astragalus saponins
  • Cytokines
  • Lipopolysaccharide
  • Mitogen-Activated Protein Kinase
  • Nitric Oxide
  • Nuclear Factor-κ B

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