4.5 Article

The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells

Journal

INFLAMMATION
Volume 40, Issue 2, Pages 401-413

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-016-0485-1

Keywords

withaphysalin A; 2, 3-dihydro-withaphysalin C; inflammatory diseases; RAW264.7; lipopolysaccharide; nitric oxide

Funding

  1. National Natural Science Foundation of China [81430092]
  2. program for New Century Excellent Talents in University [NCET-2013-1015]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
  4. Ph.D. Programs Foundation of Ministry of Education of China [20120096130002]

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Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E-2 (PGE(2)), and several pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-kappa B p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.

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