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

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.

• Authors: Regina Lin, Hyoungsu Kim, Jiyong Hong, Qi-Jing Li
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 5 Issue 5 Pg. 485-90 (May 08 2014) ISSN: 1948-5875 [Print] United States
• PMID: 24900866 (Publication Type: Journal Article)