STAT-1 as a new molecular target of anti-inflammatory treatment.

Cyclooxygenase (COX) is widely considered as the molecular target of non-steroid anti-inflammatorydrugs (NSAIDs). However, due to the harmful side effect frequently observed following chronic use, thedevelopment of new anti-inflammatory agents is the matter of many studies.Signal transducers and activators of transcription (STAT) are a family of nuclear proteins mediating the action ofa number of cytokines. Among them, STAT1 plays a critical role in the signal transduction pathway ofinterferon-gamma (IFN-gamma) and growth hormone. STAT1 cascade is one major signalling pathwayconverting the IFN-gamma signal into gene expression, such as inducible nitric oxide synthase (iNOS), COX,vascular cell adhesion molecules (VCAM) and intercellular cell adhesion molecules (ICAM), critically involvedin different pathologies correlated to the inflammatory process.This review focuses the attention on an alternative approach to the development of novel drugs based oninhibition of STAT1 pathway.In this context, a growing interest has been focused on natural compounds. We have recently reported a severaldata indicating that green tea extract (GTE), St. John’s Wort extract and epigallocatechin-3-gallate (EGCG)exhibit a specific and strong anti-STAT1 activity which is independent of their acclaimed strong anti-oxidantactivity. More recently, GTE has been shown to protect heart damage from ischaemia/reperfusion in rats,suggesting that the protective effect of green tea might be correlated to its anti-STAT1 activity.The present review is aimed at providing data that STAT1 may potentially be claimed as a new molecular targetof an anti-inflammatory treatment and that among natural compounds there are a number of anti-STAT1substances.