2. Academic Validation
  3. Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention

Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention

  • ACS Med Chem Lett. 2014 Mar 12;5(5):485-90. doi: 10.1021/ml4004809.
Regina Lin 1,  Hyoungsu Kim 2,  Jiyong Hong 3,  Qi-Jing Li 1
Affiliations

Affiliations

  • 1 Department of Immunology, Duke University Medical Center , Durham, North Carolina 27710, United States.
  • 2 Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
  • 3 Department of Chemistry, Duke University , Durham, North Carolina 27708, United States ; Department of Pharmacology and Cancer Biology, Duke University Medical Center , Durham, North Carolina 27710, United States.
PMID: 24900866 DOI: 10.1021/ml4004809
Abstract

Subglutinol A (1) is an immunosuppressive natural product isolated from Fusarium subglutinans, an endophytic fungus from the vine Tripterygium wilfordii. We show that 1 exerts multimodal immune-suppressive effects on activated T cells in vitro: subglutinol A (1) effectively blocks T cell proliferation and survival while profoundly inhibiting pro-inflammatory IFNγ and IL-17 production by fully differentiated effector Th1 and Th17 cells. Our data further reveal that 1 may exert its anti-inflammatory effects by exacerbating mitochondrial damage in T cells. Additionally, we demonstrate that 1 significantly reduces lymphocytic infiltration into the footpad and ameliorates footpad swelling in the mouse model of Th1-driven delayed-type hypersensitivity. These results suggest the potential of 1 as a novel therapeutic for inflammatory diseases.

Keywords

Subglutinol; T cell activation; immunosuppressive agent; inflammatory disease; mitochondrial dysfunction.

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