Modulation of COX, LOX and NFκB activities by Xanthium spinosum L. root extract and ziniolide

Abstract

Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses – namely diarrhoea, inflammation, liver disorders, snake bite and fever – are linked – at least in part – to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50≅10μg/mL), COX-1(IC50≅50μg/mL), and 12-LOX (IC50≅170μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2 is not probable, but the extract induced the synthesis of the anti-inflammatory eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided fractionation of the crude extract led to the isolation of ziniolide, a known 12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the n-hexane extract (IC50=69μM). Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NFκB activation, a key regulator of the arachidonic pathway.