Preventive and Therapeutic Effects of Adenanthin on Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling

Abstract

MaterialSupplementary http://www.jimmunol.org/content/suppl/2013/08/23/191.5.2115.DC1

Interaction of adenanthin with glutathione and thiol enzymes: Selectivity for thioredoxin reductase and inhibition of peroxiredoxin recycling

“…Also, although Prxs were the only adenanthinͲbinding proteins detected with leukemic cells [1] this group observed interaction with components of the NFNB signaling pathway in their model of autoimmune encephalomyelitis [2].…”

“…Indeed, the finding that Prxs did not appear to be the target in the encephalitis model [2] implies that adenanthin may not be as selective as initially proposed. In order to understand more about the biological activity of adenanthin, we have compared its reactivity with Prxs, GSH and components of the reductive pathways involved in Prx and GSH recycling.…”

“…It has also been reported to delay the development of mouse experimental autoimmune encephalomyelitis [2]. When Liu et al [1] searched for binding partners in the APL cells using biotinͲ adenanthin, their pull down experiments detected a single protein band which they showed to contain peroxiredoxins (Prxs) 1 and 2.…”

Adenanthin, a new inhibitor of thiol‐dependent antioxidant enzymes, impairs the effector functions of human natural killer cells

“…25 Hence, ADNT has arisen as a fairly potent research tool for interfering with thioldependent peroxidases. Because ADNT has been proposed to be a potential immunomodulatory 27 or anti-tumour compound, 27,28 it becomes important to identify the full spectrum of pharmacological actions of ADNT in biological systems, particularly those related to tumour surveillance. In this study, we assessed the effects of ADNT on the functions of primary human NK cells.…”

Natural products against hematological malignancies and identification of their targets

“…However, the possibility could not be excluded that adenanthin might also bind with other protein(s). Actually, we showed that adenanthin exerts effective preventive and therapeutic effects on experimental autoimmune encephalomyelitis, which might be mediated via its inhibitory action on NF-B signaling pathway [43]. More recently, it was also shown that, next to Prx I/II, adenanthin also targets and inhibits the activity of additional proteins including the thioredoxin-thioredoxin reductase (TrxR) system and protein disulfide isomerase [44], as well as glutathione (GSH) [45].…”