Ester alkaloids from Cephalotaxus interfere with the type I interferon pathway
11th International Conference on Nursing and Immunopharmacology
November 20-21, 2017 Melbourne, Australia

Ga-Young Park and Yoon-Jae Song

Gachon University, Republic of Korea

Posters & Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Inappropriate recognition of self-DNA contributes to interferonopathy and promotes autoimmune diseases like Systemic Lupus Erythematosus (SLE) and chronic polyarthritis. The cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) pathway plays an important role in production of inflammatory cytokines. To identify potential suppressors of STING-Induced type I interferon (IFN) induction, 70% ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-β promoter activation. As a result 70% ethanol extract of Cephalotaxus koreana specifically downregulated STING-induced, but not TBK1- or IRF3-induced, IFN-β promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-β promoter activation in 70% ethanol extract of Cephalotaxus koreana were identified as ester alkaloids, homoharringtonine and harringtonine. These two compounds inhibited 2�??3�??-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases.

Biography :

Ga-Young Park is currently pursuing his graduation from the Department of Life Science at Gachon University, Republic of Korea.